PubMed：

(tuberculosis[Title/Abstract]) OR (lung cancer [Title/ Abstract])

Filters applied: from 2026/05/01 - 2026/05/31.

1. Lancet. 2026 Jun 27;407(10548):2620-2629. doi: 10.1016/S0140-6736(26)00966-9.

Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in advanced squamous non-small-cell lung cancer (HARMONi-6): interim overall survival analysis of a randomized, double-blind, phase 3 trial in China.

BACKGROUND: Bispecific antibodies targeting programmed death 1 (PD-1) and vascular endothelial growth factor (PD1-VEGF) have shown promising efficacy in non-small-cell lung cancer (NSCLC). In our previous report of the HARMONi-6 study, we aimed to evaluate the efficacy and safety of ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as a first-line therapy for patients with advanced squamous NSCLC. Ivonescimab combined with chemotherapy significantly prolonged progression-free survival compared with tislelizumab plus chemotherapy. Here we report the prespecified interim overall survival analysis.

METHODS: HARMONi-6 is a double-blind, randomized, phase 3 trial, which was conducted at 50 hospitals across China. Patients aged 18-75 years with previously untreated, pathologically confirmed, unresectable stage IIIB, IIIC, or stage IV squamous NSCLC and an Eastern Cooperative Oncology Group performance status score of 0 or 1 were eligible for inclusion. Eligible patients were randomly assigned in a 1:1 ratio to receive ivonescimab or tislelizumab, in combination with paclitaxel and carboplatin for four cycles, followed by maintenance ivonescimab or tislelizumab monotherapy. The primary endpoint was progression-free survival assessed by the independent radiographic review committee as per Response Evaluation Criteria in Solid Tumours guidelines (version 1.1) in all randomly assigned patients. Overall survival was a key secondary endpoint; an interim analysis was planned when approximately 225 overall survival events were observed, but it was triggered after 204 overall survival events to meet regulatory deadlines. Safety, defined as adverse events and serious adverse events related to treatment, as well as adverse events related to immunity or VEGF blockade, were analysed in all randomly assigned patients who received at least one dose of the assigned study treatment. This study is registered at ClinicalTrials.gov (NCT05840016), has completed enrolment, and is ongoing for treatment and follow-up.

FINDINGS: From Aug 17, 2023, to Jan 21, 2025, 761 patients were assessed for eligibility, and after 229 exclusions a total of 532 patients were randomly allocated (266 per group). 494 (93%) of patients were male and 38 (7%) of patients were female. The median age was 64 years (IQR 59-69). At data cutoff (Feb 27, 2026), 204 deaths had occurred: 84 (32%) patients in the ivonescimab plus chemotherapy group and 120 (45%) in the tislelizumab plus chemotherapy group. With a median follow-up of 21·4 months (95% CI 20·27-21·91), the median overall survival was 27·9 months (95% CI 27·89-not evaluable [NE]) with ivonescimab versus 23·7 months (20·11-NE) with tislelizumab (hazard ratio for death 0·66 [95% CI 0·50-0·87]; pone-sided=0·0017), meeting the prespecified boundary (p<0·0049). The overall survival benefit with ivonescimab plus chemotherapy was consistent across key subgroups. Treatment-related adverse events of grade 3 or higher occurred in 184 (69%) of 266 patients in the ivonescimab group and 156 (59%) of 265 patients in the tislelizumab group. The incidence of grade 3 or higher haemorrhage was seven (3%) of 266 and two (1%) of 265, respectively.

INTERPRETATION: Ivonescimab plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival compared with tislelizumab plus chemotherapy in previously untreated patients with advanced squamous NSCLC. This regimen could provide a novel treatment option as first-line treatment in this patient group.

PMID: 42218899 [Indexed for MEDLINE]

2. Lancet. 2026 Jun 27;407(10548):2607-2619. doi: 10.1016/S0140-6736(26)00968-2.

Sacituzumab tirumotecan plus pembrolizumab versus pembrolizumab in PD-L1-positive advanced non-small-cell lung cancer (OptiTROP-Lung05): interim analysis of a randomized, open-label, phase 3 trial.

BACKGROUND: Sacituzumab tirumotecan (sac-TMT), a trophoblast cell-surface antigen 2-targeting antibody-drug conjugate, combined with programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors, has shown promising antitumour activity as first-line therapy for non-small-cell lung cancer (NSCLC) in early-phase studies. Our aim was to evaluate the efficacy and safety of sac-TMT plus pembrolizumab as first-line treatment for patients with PD-L1-positive advanced NSCLC without targetable genomic alterations.

METHODS: In this randomized, open-label, phase 3 trial (OptiTROP-Lung05) conducted across 68 hospitals in China, eligible patients had locally advanced or metastatic NSCLC without targetable genomic alterations and a PD-L1 tumour proportion score (TPS) of 1% or greater. Patients were randomly assigned (1:1) to receive sac-TMT (4 mg/kg on days 1, 15, and 29) plus pembrolizumab (400 mg fixed dose on day 1), or pembrolizumab alone, administered intravenously every 6 weeks. The primary endpoint was progression-free survival, as assessed by blinded independent central review in the intention-to-treat population. This trial was registered with ClinicalTrials.gov (NCT06448312). Recruitment is complete, with the trial ongoing and the final analysis to be reported later.

FINDINGS: Between June 7, 2024, and March 27, 2025, 741 patients were screened and 413 eligible patients were randomly assigned to receive sac-TMT plus pembrolizumab (n=208) or pembrolizumab alone (n=205). At the prespecified interim analysis, conducted after a median follow-up of 10·5 months (IQR 8·7-12·5), median progression-free survival was significantly longer with sac-TMT plus pembrolizumab than with pembrolizumab alone (not reached vs 5·7 months; stratified hazard ratio [HR] 0·35 [95% CI 0·26-0·47]; p<0·0001). The progression-free survival benefit was broadly consistent across subgroups, including patients with PD-L1 TPS of 1-49% (HR 0·28 [95% CI 0·19-0·41]) and those with PD-L1 TPS of 50% or greater (HR 0·47 [0·29-0·77]). Grade 3 or higher treatment-emergent adverse events occurred in 115 (55%) of 208 patients in the sac-TMT plus pembrolizumab group and 64 (31%) of 204 patients in the pembrolizumab group.

INTERPRETATION: Among patients with PD-L1-positive advanced NSCLC without targetable genomic alterations, first-line treatment with sac-TMT plus pembrolizumab significantly prolonged progression-free survival compared with pembrolizumab alone. Therefore, sac-TMT plus pembrolizumab has the potential to redefine first-line treatment for patients with PD-L1-positive advanced NSCLC without targetable genomic alterations.

PMID: 42214392 [Indexed for MEDLINE]

3. JAMA. 2026 Jun 1:e268992. doi: 10.1001/jama.2026.8992. Online ahead of print.

Adjuvant Nivolumab vs Observation in Resected Non-Small Cell Lung Cancer: A Randomized Clinical Trial.

IMPORTANCE: Preoperative and perioperative nivolumab improve event-free survival in resectable non-small cell lung cancer. The role of adjuvant nivolumab after upfront surgery is unknown.

OBJECTIVE: To determine whether adjuvant nivolumab improves disease-free survival and overall survival in patients with resected non-small cell lung cancer with any tumor programmed death-ligand 1 (PD-L1) expression and in those with at least 50% PD-L1 expression.

DESIGN, SETTING, AND PARTICIPANTS: This open-label, randomized phase 3 study enrolled participants from May 2016 through September 2019, with median follow-up of 72.6 months at the data cutoff in December 2025. The study was conducted at 378 centers in the US National Clinical Trials Network. Patients were identified through a screening trial. Those with resected tumors at least 4 cm and/or who were lymph node positive (N1/N2) were eligible for inclusion after completion of planned standard adjuvant therapy if the tumor was adenocarcinoma without sensitizing sequence variants in EGFR and ALK or squamous cell carcinoma.

INTERVENTION: Patients were randomized in a 1:1 ratio to receive nivolumab 480 mg intravenously every 4 weeks for up to 1 year or standard care observation.

MAIN OUTCOMES AND MEASURES: Co-primary end points were disease-free survival in the intention-to-treat population and in those with tumoral PD-L1 expression at least 50%. Overall survival was examined if the corresponding test of disease-free survival was statistically significant.

RESULTS: A total of 466 patients (median age, 66 years; 241 [52%] male) were assigned to receive nivolumab and 469 (median age, 67 years; 245 [52%] male) to undergo standard care observation. The median duration of follow-up was 72.6 months. The trial was stopped for futility at 75% information. In the intention-to-treat population, median disease-free survival was 71.3 months with nivolumab and 68.8 months with observation (hazard ratio for progression or death, 0.97 [97% CI, 0.79-1.20]; [95% CI, 0.81-1.17]; 1-sided P = .39). In the subset of participants with PD-L1 of at least 50%, median disease-free survival was 89.8 months with nivolumab and 78.5 months with observation (hazard ratio for progression or death, 0.86 [98% CI, 0.55-1.34]; [95% CI, 0.59-1.25]; 1-sided P = .22).

CONCLUSIONS AND RELEVANCE: Adjuvant nivolumab was not associated with improved disease-free survival in patients with resected non-small cell lung cancer without sensitizing EGFR and ALK alterations when given after planned adjuvant chemotherapy and/or radiotherapy.

PMID: 42224490

4. Nat Med. 2026 Jun 8. doi: 10.1038/s41591-026-04469-5. Online ahead of print.

Electronic cigarette use after smoking cessation and lung cancer risk.

Electronic cigarettes (e-cigarettes) have gained popularity as a less harmful alternative to conventional cigarettes, yet their associations with lung cancer risk after smoking cessation remain uncertain. Here we evaluated 4,524,895 adults with a conventional smoking history who participated in the Korean National Health Screening Program in 2018 (baseline), with prior records from 2012-2014. Participants were classified as current smokers, short-term quitters or long-term quitters, and followed up to December 2023. Daily e-cigarette use at baseline was used to define post-cessation e-cigarette use. Lung cancer incidence and lung cancer-specific death (LCSD) were assessed using multivariable Cox models. Over 24,182,543 person-years, 35,887 lung cancers and 12,807 LCSD events occurred. Compared with complete quitters, e-cigarette use after smoking cessation was associated with higher risks of lung cancer incidence (adjusted hazard ratio (aHR) 1.56, 95% confidence interval (CI) 1.24-1.97) and LCSD (aHR 2.00, 95% CI 1.28-3.15). Associations were directionally consistent in short-term and long-term quitters and were prominent in the high-risk subgroup (incidence: aHR 1.91, 95% CI 1.44-2.53; LCSD: aHR 1.92, 95% CI 1.13-3.24). Although causality cannot be established, these findings suggest that e-cigarette use after smoking cessation may attenuate the benefits of complete cessation for lung cancer prevention.

PMID: 42260103

5. N Engl J Med. 2026 Jun 25;394(24):2429-2439. doi: 10.1056/NEJMoa2503687.

A Pragmatic Trial of a 6-Month Strategy for Rifampicin-Resistant Tuberculosis.

BACKGROUND: Safer, more effective treatment regimens for rifampicin-resistant tuberculosis are needed.

METHODS: We conducted a phase 3, open-label, pragmatic, randomized, controlled noninferiority trial in South Africa to assess a 6-month treatment strategy for pulmonary rifampicin-resistant tuberculosis. Participants with pulmonary rifampicin-resistant tuberculosis who were 6 years of age or older were randomly assigned to a regimen consisting of bedaquiline, linezolid, delamanid, and levofloxacin or clofazimine or both for 6 months (trial-strategy group) or the 9-month standard-of-care treatment regimen that was current in South Africa (control group). Persons who were pregnant or breastfeeding and those who had fluoroquinolone-resistant tuberculosis were included in the trial population. Treatment in both groups was adjusted on the basis of results of second-line drug susceptibility testing. The primary efficacy end point was a successful outcome (cure or completion of treatment) at the end of treatment and at 76 weeks after randomization. The noninferiority margin was 10 percentage points. The primary safety end point was an adverse event of grade 3 or higher.

RESULTS: Among the 432 persons who were screened, 403 underwent randomization; 203 were assigned to the trial-strategy group, and 200 to the control group. A successful outcome was observed in 174 of 202 participants (86.1%) in the trial-strategy group and in 172 of 200 (86.0%) in the control group. The adjusted risk difference was -0.2 percentage points (95% confidence interval [CI], -6.9 to 6.5; P = 0.001 for noninferiority). Adverse events of grade 3 or higher occurred during treatment in 63 of 202 participants (31.2%) in the trial-strategy group and in 74 of 200 (37.0%) in the control group; 10 participants in each group died.

CONCLUSIONS: Among participants in South Africa with rifampicin-resistant tuberculosis, the 6-month trial strategy was noninferior to the standard-of-care strategy with respect to a successful outcome. The safety profiles of the two strategies were similar. (Funded by the U.S. Agency for International Development and others; BEAT Tuberculosis ClinicalTrials.gov number, NCT04062201.).

PMID: 42341301 [Indexed for MEDLINE]

6. Immunity. 2026 Jun 23:S1074-7613(26)00228-1. doi: 10.1016/j.immuni. 2026.05. 017. Online ahead of print.

Monocytic niches escape T cell surveillance and promote Mycobacterium tuberculosis persistence in lymph nodes.

Lung-draining mediastinal lymph nodes (medLNs) are critical for Mycobacterium tuberculosis (Mtb) pathogenesis, serving both as sites of T cell priming and, paradoxically, reservoirs for long-term bacterial persistence. To understand this dichotomy, we examined myeloid and CD4+ T cell dynamics in medLNs after aerosol Mtb infection. Early bacterial dissemination occurred via monocytes and interleukin (IL)-12-producing conventional dendritic cells (cDCs), which initiated T helper 1 (Th1) cell priming within the T cell zone. Over time, cDC migration and T cell activation declined, and medLNs became dominated by heavily infected monocyte-derived aggregates that persisted into late infection. Despite inducing proinflammatory and bactericidal pathways, these aggregates escaped recognition by Mtb-specific T cells and failed to clear Mtb, thereby forming an immunologically "blind" niche. Bacille Calmette-Guérin (BCG) vaccination reduced Mtb burden and niche establishment without altering myeloid trafficking or T cell priming. Thus, Mtb persists in medLNs within monocytic niches, eliciting classical antimicrobial programs that are insufficient for sterilizing control.

PMID: 42335893

7. Nat Microbiol. 2026 Jun;11(6):1696-1710. doi: 10.1038/s41564-026-02357-9.

Transcription attenuation amplifies collateral vulnerabilities in rifampicin-resistant Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) acquires resistance to rifampicin (Rif) through mutations in the β-subunit of RNA polymerase (RNAP) that prevent the drug from binding. The most common mutation is a single amino acid substitution, βS450L, that confers antibiotic resistance. This mutation also results in collateral effects that impact bacterial physiology and fitness, although the mechanisms underlying many of these effects remain unclear. Here we employed a CRISPRi comparative functional genomics approach to analyse gene vulnerability differences between βS450L Mtb and two alternative Rif-resistant (RifR) Mtb strains, βD435V and βH445Y. Among the strongest βS450L-specific vulnerabilities, we identified thiamine and branched-chain amino acid (BCAA) biosynthesis pathways. These vulnerabilities arise, at least in part, due to transcription attenuation, which impairs βS450L Mtb's ability to upregulate expression of the critical BCAA biosynthetic enzyme ilvB1 in response to genetic or chemical inhibition. Together, our findings highlight the distinct physiological impacts of RifR in Mtb, identify transcription attenuation as a key driver of βS450L-specific vulnerabilities, and suggest potential avenues for targeted intervention.

PMID: 42156950 [Indexed for MEDLINE]

8. Lancet Infect Dis. 2026 Jun;26(6):e248-e256. doi: 10.1016/S1473-3099(25)00547-X.

Future-proofing tuberculosis therapy: framework for concurrent drug and resistance testing development.

The rapid emergence of resistance to novel tuberculosis drugs, such as bedaquiline, is a key threat to the long-term effectiveness of novel regimens. Given that the introduction of these agents has enabled the introduction of an all-oral regimen for rifampicin-resistant and multidrug-resistant tuberculosis, the rise of resistance underscores the urgent need to safeguard their efficacy and responsible use. A major barrier is the delay in developing reliable tools to detect resistance to novel compounds, which limits clinical decision-making and surveillance efforts. Herein, we outline a framework for integrating the development of drug susceptibility testing alongside tuberculosis drug development, including early stage resistance profiling and defining appropriate epidemiological cutoff values. We highlight key gaps, including the need for structured partnerships between drug developers, diagnostic manufacturers, regulators, research institutions, funders, and policy makers. We propose a roadmap to accelerate drug susceptibility testing and development of new tuberculosis regimens, ensuring that resistance detection maintains pace with the introduction of novel drugs. Establishing collaborative platforms for data sharing, genomic analysis, and diagnostic innovation will help ensure that resistance detection evolves in step with drug development, thereby preserving novel treatments and improving global tuberculosis care.

PMID: 42223242 [Indexed for MEDLINE]

9. Nat Med. 2026 Jun 1. doi: 10.1038/s41591-026-04452-0. Online ahead of print.

SEZ6-targeting antibody-drug conjugate ABBV-706 in advanced small cell lung cancer and solid tumors: a phase 1 trial.

Seizure-related homolog 6 (SEZ6) is expressed in small cell lung cancer (SCLC) and neuroendocrine neoplasms. In an open label, phase 1 trial, ABBV-706, an antibody-drug conjugate with a SEZ6-directed antibody linked to topoisomerase-1 inhibitor (Top1i), was administered intravenously every 3 weeks (Q3W) to 288 patients with advanced solid tumors; 240 received monotherapy, including 124 with relapsed/refractory (R/R) SCLC. Primary objectives of dose escalation (part 1, advanced solid tumors), dose optimization and expansion (part 2, R/R SCLC only) and dose expansion (part 4, central nervous system tumors and high-grade neuroendocrine neoplasms only) were to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity and antitumor activity of ABBV-706 monotherapy and, from parts 1 and 2, to determine the recommended phase 2 dose (RP2D) of ABBV-706 in R/R SCLC. In the monotherapy cohort (N = 240), the most common treatment-related adverse events (TRAEs) at any grade were anemia (61%) and fatigue (38%). Grade 3 or higher TRAEs occurred in 61% of patients and were dose dependent (39% at 1.8 mg kg-1 and 70% at 2.5 mg kg-1). In the R/R SCLC monotherapy cohort (n = 124), any-grade and grade 3 or higher TRAEs occurred in 93% and 61% of patients, respectively. ABBV-706 demonstrated promising preliminary efficacy in patients with R/R SCLC, with an objective response rate (ORR) of 52% (65/124). In patients with R/R SCLC receiving monotherapy in dose optimization and expansion part 2, ORR was similar between 1.8 mg kg-1 and 2.5 mg kg-1 doses (56% (23/41) and 59% (23/39), respectively), with a duration of response that was highest at the 1.8 mg kg-1 dose and with most patients achieving rapid and durable tumor reduction. Although exploratory, long-term efficacy measures were an important consideration in the RP2D determination, and in R/RSCLC monotherapy, overall survival (OS) was highest at the 1.8 mg kg-1 dose, with a median OS of 12.4 months. Based on the totality of available data, including, but not limited to, safety, preliminary efficacy measures and PK, 1.8 mg kg-1 Q3W was confirmed as the optimal RP2D for patients with R/R SCLC. ClinicalTrials.gov: NCT05599984 .

PMID: 42225988

10. J Clin Oncol. 2026 Jun 10;44(17):1635-1645. doi: 10.1200/JCO-25-02016.

First-in-Human, Phase I Study of Sigvotatug Vedotin, an Integrin Beta-6-Directed Antibody-Drug Conjugate: Results From Dose Expansion in Advanced Non-Small Cell Lung Cancer.

PURPOSE: Integrin beta-6 (IB6) is highly expressed in non-small cell lung cancer (NSCLC) and other solid tumors and potentially associated with poor outcomes. Sigvotatug vedotin (SV), a novel IB6-directed antibody-drug conjugate, demonstrated acceptable safety and encouraging antitumor activity in dose escalation. We report updated results for dose-expansion regimens in advanced NSCLC (aNSCLC).

METHODS: SGNB6A-001 is an open-label, multicenter, dose-escalation/dose-expansion phase I study evaluating safety, tolerability, pharmacokinetics (PK), and antitumor activity of SV in patients with select advanced solid tumors. After dose escalation, dose expansion further explored three regimens: 1.25 mg/kg total body weight (TBW) on Days 1 and 8 of a 21-day cycle, 1.5 mg/kg TBW on Days 1 and 15 of a 28-day cycle (once every 2 weeks), and 1.8 mg/kg adjusted ideal body weight (AiBW) once every 2 weeks. Eligible patients had prior chemotherapy and immunotherapy or targeted therapy if indicated. Primary end points were safety and determination of an optimal dosing schedule. Secondary end points were antitumor activity, PK, and immunogenicity.

RESULTS: As of November 26, 2024, 117 patients with aNSCLC were treated in the above cohorts. Any-grade and grade ≥3 treatment-emergent adverse events occurred in 98% and 48% of all patients, respectively, and in 94% and 35% of patients receiving SV 1.8 mg/kg AiBW once every 2 weeks. Modeling revealed that the AiBW regimen resulted in lower PK variability than TBW regimens. The objective response rate and median duration of response were 19% and 11.3 months in the overall population, respectively, and 29% and 12.8 months in patients with nonsquamous, taxane-naïve NSCLC.

CONCLUSION: SV demonstrated a manageable safety profile and promising antitumor activity with durable responses in aNSCLC. PK and clinical data support further investigation with the recommended 1.8-mg/kg AiBW once every 2 weeks dosing regimen.

PMID: 42008777 [Indexed for MEDLINE]

11. Ann Intern Med. 2026 Jun 30. doi: 10.7326/ANNALS-25-03816.

Performance of Lung Cancer Risk Prediction Models in Different Racial and Ethnic Groups in the United States: Results From the Lung Cancer Cohort Consortium.

BACKGROUND: Racial and ethnic disparities are a concern in lung cancer screening.

OBJECTIVE: To investigate the performance of risk prediction models to define screening eligibility across 4 U.S. racial and ethnic groups.

DESIGN: Cohort study.

SETTING: United States, Lung Cancer Cohort Consortium.

PARTICIPANTS: 641 830 participants aged 50 to 80 years with a smoking history from 12 U.S. cohorts, including 6390 Asian, 9781 Hispanic, 39 872 non-Hispanic Black, and 585 787 non-Hispanic White participants.

MEASUREMENTS: Calibration and discrimination were quantified for 16 lung cancer prediction models. Then, screening-related metrics were calculated after applying model thresholds to select the same number of eligible participants as the 2021 criteria from the U.S. Preventive Services Task Force (USPSTF-2021). These included eligibility, sensitivity, and efficiency measured as estimated number needed to screen (NNS; the ratio between participants and lung cancer cases) for each strategy or prediction model in each racial and ethnic group.

RESULTS: General patterns across the 16 models included substantial underestimation of lung cancer risk in non-Hispanic Black participants (expected-observed ratio < 0.75 for 11 of 16 models), lower discrimination in Asian participants than all other groups (13 of 16 models), and lower discrimination in non-Hispanic Black than non-Hispanic White participants (15 of 16 models). When a same-sized screening-eligible population as USPSTF-2021 (38.0%) was enforced, all risk-based strategies achieved better average estimated screening efficiency and reduced racial and ethnic differences in efficiency compared with USPSTF-2021. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Model 2012 (PLCOm2012) and Life Years gained From Screening-Computed Tomography model (LYFS-CT) performed best (mean estimated NNS, 36.5 [SD, 8.8] and 40.1 [SD, 8.2], respectively). However, no strategy could simultaneously optimize eligibility, sensitivity, and efficiency while also reducing racial and ethnic differences.

LIMITATION: Smaller sample for Asian and Hispanic participants.

CONCLUSION: To optimize efficiency and minimize its variation across racial and ethnic groups, risk-based strategies were superior to USPSTF criteria. Further optimization of prediction models for the diverse U.S. population is needed.

PMID: 42372272

12. Nat Med. 2026 Jun;32(6):2245-2253. doi: 10.1038/s41591-026-04323-8.

Gotistobart or docetaxel in metastatic squamous non-small cell lung cancer: stage 1 of the randomized phase 3 PRESERVE-003 trial.

PRESERVE-003 is a two-stage phase 3 trial evaluating gotistobart (BNT316/ONC-392), a novel pH-sensitive anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) antibody that selectively depletes regulatory T cells within the tumor microenvironment, in patients with metastatic squamous non-small cell lung cancer (sqNSCLC) without actionable genomic alterations who progressed on programmed cell deathprotein/programmed death ligand 1 inhibitor/platinum-based chemotherapy-a population with a poor prognosis. Here we report on stage 1, which aimed to confirm the dose and assess the preliminary efficacy (primary outcome: overall survival; secondary outcomes: progression‑free survival, objective response rate and duration of response) and safety of gotistobart compared to docetaxel. Patients with sqNSCLC were randomized (1:1) to gotistobart (6 mg kg-1 with two 10 mg kg-1 loading doses every 3 weeks (N = 45)) or docetaxel (75 mg m-2 every 3 weeks (N = 42)). After a median follow-up of 14.5 months, median overall survival was not reached with gotistobart (95% confidence interval (CI) 9.3 to not evaluable) versus 10.0 months (95% CI 6.2 to 11.9 months) with docetaxel (hazard ratio 0.46, 95% CI 0.25 to 0.84, nominal two-sided P = 0.0102). Safety was manageable, with grade ≥3 treatment-related adverseevents in 42% and 49% of patients receiving gotistobart and docetaxel, respectively. Stage 1 results suggest that gotistobart monotherapy can provide clinically meaningful benefit for patients with programmed cell death protein/programmed death ligand 1-resistant and chemotherapy-resistant metastatic sqNSCLC. ClinicalTrials.gov identifier: NCT05671510 .

PMID: 41896648 [Indexed for MEDLINE]

13. Nat Immunol. 2026 Jun 12. doi: 10.1038/s41590-026-02545-z.

mRNA-based tuberculosis vaccines BNT164a1 and BNT164b1 are immunogenic, well tolerated and efficacious in rodent models.

We designed and preclinically tested two mRNA-lipid-nanoparticle-based vaccine candidates to protect against tuberculosis. BNT164a1 and BNT164b1 encode the same eight Mycobacterium tuberculosis antigens expressed across different infection stages: Ag85A, Hrp1, ESAT-6, RpfD, RpfA, HbhA, M72 and VapB47. BNT164a1 utilizes nucleoside-unmodified mRNA, whereas BNT164b1 utilizes N1-methylpseudouridine-modified mRNA. Prime-boost immunization with BNT164 candidates elicited antibody and/or T cell responses against all antigens in three mouse strains (C57BL/6, BALB/c and HLA-A2.1/DR1 humanized mice). The candidates demonstrated favorable safety profiles in a rat toxicity study and significantly reduced bacterial burdens of two M. tuberculosis strains in murine aerosol challenge models. BNT164 protection was correlated with granuloma infiltration by CD8+ T cells with memory precursor phenotypes. In conclusion, BNT164a1 and BNT164b1 were immunogenic, well tolerated and efficacious in preclinical models and have entered phase 1/2 clinical trials ( NCT05537038 , NCT05547464 ).

PMID: 42286358

14. Clin Microbiol Rev. 2026 Jun 11;39(2):e0035325. doi: 10.1128/cmr.00353-25.

Management of latent tuberculosis infection in patients with kidney disease.

SUMMARYLatent tuberculosis infection (LTBI) is common and preventable among patients with chronic kidney disease (CKD), where uremia and iatrogenic immunosuppression heighten reactivation risk. This narrative review synthesizes evidence across pre-dialysis CKD, dialysis, and kidney transplantation to propose a pragmatic care pathway. In advanced CKD, the tuberculin skin test performs poorly, whereas interferon-γ release assays (IGRAs) are preferred. Screening should be risk-targeted in pre-dialysis CKD, systematic at dialysis initiation, and mandatory pre-transplant for candidates and living donors. Following a positive test, clinicians must exclude active tuberculosis via clinical assessment and chest imaging before starting preventive therapy. Short-course rifamycin-based regimens (4 months of daily rifampin [4R], 3 months of once‑weekly isoniazid plus rifapentine [3HP], or 3 months of daily isoniazid plus rifampin [3HR]) enhance completion rates compared with 9 months of daily isoniazid (9H). In transplant recipients, rifamycin interactions with calcineurin and Mammalian target of rapamycin (mTOR) inhibitors typically favor 9H; rifamycins demand expert multidisciplinary management with intensive therapeutic drug monitoring. Programmatic data from dialysis units show high completion with tolerable toxicity, affirming routine feasibility. We integrate IGRA-based screening at critical transitions with tailored regimen selection, pyridoxine coadministration for isoniazid, and structured safety monitoring. Priorities include validating novel Mycobacterium tuberculosis antigen-based skin tests in CKD and developing implementation strategies to standardize renal care. We delineate setting-specific approaches for high- versus low-burden countries, addressing subclinical and incipient TB challenges in high-burden contexts. Adopting this framework can curb active TB progression, safeguard grafts, and enhance patient outcomes.

PMID: 42007724 [Indexed for MEDLINE]

15. Lancet Respir Med. 2026 Jun;14(6):505-520. doi: 10.1016/S2213-2600(26)00056-1.

PET-CT benchmarked detection and 5-year progression of asymptomatic tuberculosis: a longitudinal, prospective cohort study.

BACKGROUND: To understand how lung pathology relates to symptoms, microbiology, and progression risk in tuberculosis and to advance diagnostic development, we determined the frequency at screening of tuberculosis-consistent lesions in asymptomatic individuals within 5 years of tuberculosis diagnosis using highly sensitive imaging ([18F]-fluorodeoxyglucose PET-CT) and compared with chest x-ray computer-aided detection (CAD).

METHODS: We enrolled a prospective longitudinal cohort in Khayelitsha, Cape Town, South Africa, of asymptomatic, HIV-uninfected contacts aged 18-65 years of patients with rifampicin-resistant tuberculosis, a tuberculosis high-risk group not eligible for chemoprophylaxis. Participants underwent baseline PET-CT, chest x-ray, phlebotomy, and intensive sputum collection, and were classified into four PET-CT lung categories: consistent with tuberculosis, inactive tuberculosis, other lesions, and normal. Chest x-ray was processed by three types of CAD software (CAD4TB [version 7.0], qXR [version 3.0.0], and Lunit [version 3.1.4.111]). Follow-up included symptom-agnostic tuberculosis screening (23-38 months) and provincial register review (≤74 months), and a subgroup had repeat PET-CT (5-15 months). Tuberculosis was defined as bacteriologically confirmed or clinically diagnosed. The primary outcome measures were hazard ratio (HR) for tuberculosis diagnosis and treatment by baseline PET-CT lung abnormality category with normal as the reference group, and diagnostic performance of chest x-ray CAD software using area under the receiver operator characteristic curve (AUC).

FINDINGS: 250 asymptomatic adults were enrolled between March 3, 2015, and Oct 11, 2017, irrespective of tuberculosis history or previous infection, and followed up for 1107 person-years (median 4·7 years [IQR 4·0-5·1]). 18 (7%) participants were treated for tuberculosis (16 [89%] of 18 bacteriologically confirmed). Six of 18 participants were diagnosed at baseline (four requiring induced sputum culture) and 12 of 18 after a median of 32 months (IQR 12-35). By baseline PET-CT category, tuberculosis was diagnosed and treated in 12 (41%) of 29 participants with scans consistent with tuberculosis, two (7%) of 30 with scans consistent with inactive tuberculosis, two (2%) of 83 with scans showing other lesions, and two (2%) of 108 with scans showing normal lungs. Participants with baseline PET-CT scans consistent with tuberculosis had the highest risk of 5-year tuberculosis diagnosis (HR 28·54 [95% CI 6·37-127·81] compared with those with scans showing normal lungs, p<0·0001), with no significant risk for scans consistent with inactive tuberculosis (3·55 [0·50-25·21], p=0·21) or other lung lesions (1·30 [0·18-9·23], p=0·79). 11 (69%) of the 16 participants with bacteriologically confirmed tuberculosis were asymptomatic at bacteriological confirmation, and ten (91%) of 11 had baseline PET-CT scans consistent with tuberculosis. Using baseline PET-CT classification as reference, the AUC for chest x-ray CAD software ranged from 0·86 (95% CI 0·72-0·99) to 0·89 (0·75-1·00) for bacteriologically confirmed tuberculosis.

INTERPRETATION: Most adult asymptomatic contacts diagnosed with tuberculosis over 5 years had baseline radiographically evident disease, not radiographically negative incipient tuberculosis. Although PET-CT is not feasible for routine screening, it provides a highly sensitive reference benchmark for diagnostic development, with chest x-ray CAD performing comparatively well.

PMID: 41887246 [Indexed for MEDLINE]

16. Clin Microbiol Rev. 2026 Jun 11;39(2):e0025825. doi: 10.1128/cmr.00258-25.

From T-cell sensitization to molecular-intelligent stratification: a roadmap for precision diagnosis of latent tuberculosis infection.

SUMMARY One quarter of the world's population carries latent tuberculosis infection (LTBI), an invisible reservoir that must be drained to end the global tuberculosis (TB)epidemic. This review charts the evolution of LTBI diagnosis from the tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) to a new molecular-intelligent paradigm. At the clinical level, we propose a CD4/age-stratified, resource-matched decision framework that delivers actionable screening and sequencing strategies for people living with HIV, children, the immunosuppressed, and pregnant women. At the biomarker level, we integrate host-derived analytes (CXCL1, CCL8, IP-10, CD38+CD27⁻ T cells, and Fc-glycosylated antibodies) with pathogen-derived antigens (dormancy survival regulator [DosR], resuscitation-promoting factor [Rpf], heparin-binding hemagglutinin [HBHA], and PE/PPE) to create a three-tier index: single-analyte triage, multi-analyte confirmation, and dynamic treatment monitoring. At the technology level, we benchmark multi-omics-plus-AI models, single-molecule Simoa arrays, and microfluidic point-of-care testing (POCT) platforms for sensitivity, accessibility, and cost. High-quality cross-population validation, standardized thresholds, and resource-tiered deployment remain the principal translational bottlenecks. We call for integrated programs that combine key-population multicenter cohorts, explainable AI, and ASSURED criteria to propel LTBI management from the T-cell-sensitization era into the molecular-intelligent age. Achieving this vision within 5 years is technically feasible and will accelerate global elimination targets by enabling precision preventive therapy at an unprecedented scale.

PMID: 41910258 [Indexed for MEDLINE]

17. Nat Immunol. 2026 Jun;27(6):1104-1118. doi: 10.1038/s41590-026-02529-z.

The host immune response to Mycobacterium tuberculosis determining protection or disease progression.

Tuberculosis (TB) remains a global health issue and leading cause of death. Understanding the immune response to Mycobacterium tuberculosis infection is critical to advance TB control. Although immune factors involved in protection against TB have long been identified, these cannot predict the efficacy of TB vaccines, nor which individuals will control the infection or progress to active TB disease. This is especially challenging given the complexity of M. tuberculosis infection states and the breadth of TB disease severities, which is increasingly apparent from basic, clinical and translational research. Here, we discuss the evolving spectrum of M. tuberculosis infection outcomes and TB disease, how the host immune response determines and unfolds across this spectrum and how the natural diversity of M. tuberculosis contributes to this complexity. Integration of these new concepts with fast-evolving systems immunology approaches holds great potential to inform the design of novel strategies to control TB.

PMID: 42151479 [Indexed for MEDLINE]

18. Lancet Glob Health. 2026 Jun;14(6):103902. doi: 10.1016/S2214-109X(26)00017-3. Epub 2026 Jun 8.

Inclusion of young adolescents in policy development for new tuberculosis vaccines.

The infant tuberculosis vaccine, BCG, prevents severe tuberculosis disease, but protection is rarely durable beyond childhood. New tuberculosis vaccines are being developed for the prevention of infectious pulmonary tuberculosis in older adolescents and adults, but younger adolescents have been historically excluded from clinical trials of new tuberculosis vaccines. Reasons to include young adolescents (aged 9-14 years) in tuberculosis vaccine policy development include the opportunity to vaccinate before the age-related increase in risk of tuberculosis disease, as well as increased rates of HIV acquisition and pregnancy, which are both independently associated with tuberculosis risk, and the opportunity to implement tuberculosis vaccination with delivery of other school-age vaccines, such as human papillomavirus. These advantages are offset by several challenges, including testing vaccine efficacy in an age group with low rates of tuberculosis case accrual; low rates of Mycobacterium tuberculosis sensitisation, which might compromise bridging of immune correlates of protection from adults; and modest modelled population impact of vaccination of young adolescents, compared with mass campaigns in older age groups with higher tuberculosis incidence. Notably, if a tuberculosis vaccine that was effective only in individuals who are infected with M tuberculosis was rolled out exclusively to young adolescents, the projected low population impact could take many years to detect. We propose that challenges to the inclusion of young adolescents should be considered explicitly in the development of tuberculosis vaccine policy, so that they do not risk exclusion from the direct benefits of vaccination. We describe an alternative efficacy trial design, which would leverage higher rates of tuberculosis case accrual after recent household tuberculosis exposure, to deliver both vaccine efficacy data and validation of an immune correlate of protection. This novel strategy, together with licensure data from older populations, might support rapid implementation of new, effective tuberculosis vaccines for young adolescents.

PMID: 42259345 [Indexed for MEDLINE]

19. Lancet Infect Dis. 2026 Jun;26(6):601-613. doi: 10.1016/S1473-3099(25)00747-9.

Immediate or high-dose antituberculosis therapy for HIV-related sepsis in Tanzania and Uganda (ATLAS): a phase 3, open-label, randomized, controlled, 2 × 2 factorial, superiority trial.

BACKGROUND: People living with HIV and hospitalised with sepsis in Africa are at risk of death due to tuberculosis but diagnostics for tuberculosis might be delayed or inaccessible for people presenting for critical care. We aimed to compare the effects of immediate empirical and high-dose antituberculosis therapy on 28-day mortality in adult people living with HIV with sepsis in east Africa.

METHODS: ATLAS was a phase 3, open-label, randomized, controlled, 2 × 2 factorial, superiority trial conducted at four hospitals in Tanzania and Uganda. Participants were aged 18 years or older, living with HIV, and had been admitted to hospital with sepsis with two or more modified quick Sequential Organ Failure Assessment score criteria. Exclusion criteria were active tuberculosis or receipt of antituberculosis therapy within 6 months of hospitalisation, pregnancy or lactation, allergies to antituberculosis therapy, another investigational drug within the past month, chronic liver disease, heavy alcohol use, positive serum cryptococcal antigen, or anticipated significant drug-drug interaction with rifampicin. A computer-generated permuted-block algorithm with allocation concealment and random block sizes of four and eight randomly assigned participants (1:1) to receive either immediate or diagnosis-dependent antituberculosis therapy, and (1:1) to receive either high-dose or conventional WHO-recommended weight-based dose antituberculosis therapy. Allocation was stratified by country and the presence of altered mental status at the time of randomisation. Participants randomly assigned to conventional-dose antituberculosis therapy received fixed-dose combination tablets of rifampicin approximately 10 mg/kg, isoniazid approximately 5 mg/kg, pyrazinamide, and ethambutol, plus pyridoxine 50 mg orally. Participants randomly assigned to receive high-dose antituberculosis therapy received rifampicin approximately 30 mg/kg and isoniazid approximately 7·5 mg/kg as a combination of single formulation tablets and fixed-dose combination tablets that included WHO-recommended weight-based doses of pyrazinamide and ethambutol, plus pyridoxine. Participants continued immediate antituberculosis therapy for 28 days. All medications were administered daily. Participants in the diagnosis-dependent antituberculosis therapy groups received treatment based on a clinical or microbiological diagnosis of tuberculosis. All participants received 2 g intravenous ceftriaxone daily for 7 days. The primary endpoint was 28-day mortality analysed in the modified intention-to-treat population and in the subgroup with later confirmed tuberculosis. We defined the survival time for each participant as the time from randomisation until death, discharged (alive) by day 28, or censored (alive) at day 28. We graded adverse events according to recommendations from the National Institutes of Health Division of AIDS. This study was registered with ClinicalTrials.gov, NCT04618198, and is completed.

FINDINGS: Between Jan 5, 2022, and Dec 9, 2024, 707 people were screened for eligibility and 437 were randomly assigned (110 to immediate conventional-dose, 112 to immediate high-dose, 107 to diagnosis-dependent conventional-dose, and 108 todiagnosis-dependent high-dose antituberculosis therapy). 395 patients (226 [57%] of whom were female and 169 [43%] were male; all participants were Black) received study intervention and were analysed for the primary outcome of 28-day mortality. We confirmed tuberculosis in 204 (52%) patients. There was no evidence of differences in 28-day mortality in immediate antituberculosis therapy groups (50 deaths [25%] in 198 patients) compared with diagnosis-dependent groups (50 deaths [25%] in 197 patients; adjusted hazard ratio [aHR] 0·99 [95% CI 0·67-1·46]; p=0·95), or in high-dose antituberculosis therapy groups (51 deaths [26%] in 199 patients) compared with conventional-dose groups (49 deaths [25%] in 196 patients; aHR 1·07 [0·72-1·59]; p=0·73). In patients with microbiologically confirmed tuberculosis, the 28-day mortality relative to the diagnosis-dependent conventional-dose group (18 deaths [34%] in 53 patients) was lower for the immediate conventional-dose group (six deaths [12%] in 51 participants; aHR 0·32 [95% CI 0·13-0·82]; p=0·015); for the diagnosis-dependent high-dose group (11 deaths [20%] in 56 patients) was 0·51 (0·24-1·08; p=0·079); and for the immediate high-dose group (11 deaths [26%] in 43 patients) was 0·63 (0·29-1·36; p=0·24). No significant differences in adverse events occurred between treatment groups but numerically more events of drug-induced liver injury occurred in the immediate high-dose group compared with any other group.

INTERPRETATION: Among all participants with HIV-related sepsis, 28-day mortality was not significantly reduced with immediate or high-dose antituberculosis therapy. In the subgroup with later confirmed tuberculosis, immediate conventional-dose antituberculosis therapy significantly reduced 28-day mortality, suggesting, as in other forms of bacterial sepsis, that hours to active treatment might determine survival.

PMID: 41619753 [Indexed for MEDLINE]

20. Lancet Glob Health. 2026 Jun;14(6):103935. doi: 10.1016/S2214-109X  (26)00065-3.

Global, regional, and national estimates of tuberculosis incidence averted by eliminating undernutrition in adults: a modelling study.

BACKGROUND: Current efforts to reduce global tuberculosis incidence have proved insufficient, highlighting that urgent action is needed to address underlying modifiable risk factors such as undernutrition. We aimed to estimate the global impact of eliminating undernutrition on tuberculosis incidence among adults, accounting for varying nutritional status by country, sex, and age, in addition to incorporating the continuous, non-linear relationship between BMI and tuberculosis risk.

METHODS: For this modelling study, we used a continuous risk framework to consider the population-level implications of BMI distributions for tuberculosis incidence in adults aged 15 years or older in 2023. We generated BMI distributions for each country, sex, and age group, and applied a bilinear model for the logarithmic relative risk of tuberculosis incidence at different BMI values. We assessed the impact of eliminating moderate-to-severe undernutrition (BMI<17 kg/m2) or all undernutrition (BMI <18·5 kg/m2) on tuberculosis incidence by constructing counterfactual BMI distributions that redistributed those with low BMI to high BMI, proportional to the remaining density.

FINDINGS: We estimated that eliminating moderate-to-severe undernutrition could avert 1·4 million (95% uncertainty interval 1·1-1·7) tuberculosis episodes globally, representing 14·6% (12·6-16·6) of global adult incidence in 2023, while eliminating all undernutrition could avert 2·3 million (1·8-2·7) episodes, representing a reduction in global tuberculosis incidence of 23·7% (20·9-26·5). The largest proportional reductions in tuberculosis incidence could be achieved by eliminating undernutrition in the WHO African, South-East Asia, and Eastern Mediterranean regions; in females; and in adolescents or older adults.

INTERPRETATION: Almost a quarter of global tuberculosis incidence in adults could be averted by eliminating undernutrition, approximately two-and-a-half times higher than current estimates. These findings highlight the urgent need to scale up population-level nutritional interventions, which could have myriad social and health benefits beyond tuberculosis, alongside research to establish optimal implementation strategies and impacts.

PMID: 42114532 [Indexed for MEDLINE]

21. Lancet Respir Med. 2026 Jun;14(6):521-532. doi: 10.1016/S2213-2600(26)00095-0.

Whole genome sequencing precision medicine strategy to shorten treatment for rifampicin-resistant tuberculosis (SMARTT): a pragmatic, randomized, single-blind phase 4 trial.

BACKGROUND: All patients with rifampicin-resistant tuberculosis should receive a short course of effective treatment. We aimed to evaluate the effectiveness of whole genome sequencing (WGS)-guided treatment in shortening duration of treatment for rifampicin-resistant tuberculosis.

METHODS: We did a pragmatic, randomized, single-blind phase 4 trial in 13 hospitals and 35 clinics in South Africa. Adults with pulmonary rifampicin-resistant tuberculosis were randomly assigned (1:1, using adaptive randomisation) to standard of care (WHO all-oral 9-month, seven-drug regimen or 18-month individualised regimen) or a four-drug, 6-month WGS-guided regimen generated by a feature-based artificial intelligence (AI) model. Bacteriological effectiveness, defined as difference in time to culture conversion measured as change in mycobacterial load using a non-linear mixed-effects model, was the primary outcome. Due to operational constraints and the inability toperform culture-free WGS, we performed an analysis of clinical effectiveness in a modified intention-to-treat (mITT) population (risk difference for unfavourable treatment outcomes, 10% non-inferiority margin) and safety (serious adverse events). This trial is registered with ClinicalTrials.gov, NCT05017324.

FINDINGS: 204 participants were randomly assigned between Sept 23, 2021, and Feb 9, 2023 (101 to the standard of care group, 103 to the WGS group), of which 162 culture-positive individuals were included in the mITT analysis (78 in the standard of care group, 84 in the WGS group). mITT participants were mostly male (n=120 [74%]) and living with HIV (n=100 [63%]) and had rifampicin-resistant, multidrug-resistant tuberculosis (n=142 [88%]), pre-extensively drug-resistant tuberculosis (n=15 [9%]), or extensively drug-resistant tuberculosis (n=5 [3%]). In the WGS group, 15 different individualised regimens were recommended to 81 participants, and median treatment duration was shortened by 2·6 months. Bacteriological response was similar in both groups with a mean mycobacterial load half-life of 0·30 weeks (95% CI 0·27 to 0·33) in the WGS group versus 0·31 weeks (95% CI 0·31 to 0·31) in the standard of care group (relative difference 0·97, 95% CI -0·86 to 1·07; p=0·26). Unfavourable treatment outcomes (bacteriological failure, loss to follow-up, or death) were less frequent in the WGS group (20 [24%] of 82 vs 32 [42%] of 77; adjusted risk difference -18·4 percentage points, 95% CI -35.6 to -1.2); superiority p=0.018), mostly due to reduced loss to follow-up. The frequency of serious adverse events was similar between groups (23 [27%] of 84 in the WGS group vs 26 [33%] of 78 in the standard of care group; risk difference -6% percentage points, 95% CI -8 to 20; p=0.41).

INTERPRETATION: Using WGS and AI to select regimens with optimal drug features had similar bacteriological and superior clinical efficacy compared with standard of care and was safe. Future trials should evaluate the effectiveness of culture-free sequencing-guided treatment on relapse-free cure where the standard regimen for rifampicin-resistant, multidrug-resistant tuberculosis is bedaquiline, pretomanid, linezolid, and moxifloxacin.

PMID: 42026006 [Indexed for MEDLINE]

22. Nat Immunol. 2026 Jun 24. doi: 10.1038/s41590-026-02544-0.

Airway immune signatures of protection and disease progression in recent human tuberculosis household contacts.

The local immune factors dictating whether individuals who have been infected with Mycobacterium tuberculosis remain healthy or progress to active tuberculosis (TB) have not been defined. Here we interrogated the airway immune response at single-cell resolution in bronchoalveolar lavage from positron emission and computed tomography-characterized recent TB household contacts, who either controlled the infection or progressed to TB disease, as well as of patients with active TB at diagnosis. Single-cell RNA sequencing revealed type I IFN-dependent and IFN-independent neutrophil signatures in bronchoalveolar lavage from patients with active TB and TB progressors. We report an inverse relationship between airway neutrophils and T cells, with T cells showing signatures of exhaustion, cytotoxicity and cell death in progressors and patients with active TB with a neutrophil-dominated airway profile. Conversely, we identified T cell signatures of protection in nonprogressor contacts dominated by genes related to regulation, quiescence and a stem-like profile. Our findings from early human airway responses in TB contacts reveal genes, pathways and cell states that may dictate infection outcome and inform strategies for developing effective host-directed therapies and vaccines.

PMID: 42343006

23. Nat Microbiol. 2026 Jun;11(6):1677-1695. doi: 10.1038/s41564-026-02317-3.

Lipid accumulation in tuberculosis granulomas inhibits macrophage-CD4(+) T cell interactions and infection control.

Granulomas form to contain Mycobacterium tuberculosis (Mtb) infection in the lung. What constitutes protective or detrimental responses is poorly understood. Here, using spatial transcriptomics and immunofluorescence microscopy of human lung samples and mouse models, we characterize the spatial structure and transcriptome of macrophage and T cell populations in tuberculosis granulomas. We identify signatures of reduced major histocompatibility complex (MHC) class II levels on macrophages and reduced CD4+ T cell activation, particularly in necrotic granulomas, suggesting a compromised interaction between innate and adaptive responses. Further analyses in mouse models and human cells reveal that infection of macrophages, or exposure to mycolic acids, disrupt cholesterol trafficking, leading to cholesterol accumulation and MHC class II sequestration in lysosomes. This inhibits antigen presentation and impairs anti-Mtb CD4+ T cell responses. Pharmacological restoration of cholesterol homeostasis during late-stage infection improves control of Mtb in mice. This study reveals an infection-driven mechanism of cholesterol overload, which impairs control of tuberculosis and could be targeted therapeutically.

PMID: 41933199 [Indexed for MEDLINE]

24. Adv Sci (Weinh). 2026 Jun 19:e23921. doi: 10.1002/advs.202523921.

SERS Facemask for Rapid and Portable Sensing Mycobacterium Tuberculosis Antigens for TB Screening.

Rapid and sensitive diagnostic strategies are crucial for the prevention and control of tuberculosis (TB). Unlike the invasive TB diagnostic strategy in the clinic, here we introduce a convenient, portable, and non-invasive system that is constructed by Ag@Au nanoflower (NF) array-based sensing facemask and catalytic/plasmonic urchin-shaped Au─Ag embedded covalent organic framework (U@COF) sensor. This system detects TB antigen ESAT-6/CFP-10 complex in droplet or sputum samples from a variety of clinical settings. Practical analysis of clinical samples demonstrates this assay is capable of classifying the negative (N = 12) and positive (N = 17) TB patients with satisfactory sensitivity (76.5%) and specificity (100%), among whom two TB-infected patients (TB3 and TB5) missed by droplet analysis are successfully identified by sputum analysis. More importantly, two cases with abnormally elevated ESAT-6/CFP-10 levels are screened out from close contacts of TB patients (N = 6), which is highly suggestive of TB infection (Close contacts 3 and 4). This portable mask is suitable for rapid diagnosis of TB infection in patients with cough, particularly for screening of TB close contacts.

PMID: 42318745

25. Cancer Discov. 2026 Jun 1;16(6):1055-1073. doi: 10.1158/2159-8290.CD-25-2318.

A Roadmap to Transform Lung Cancer Outcomes: Priorities in Biology, Therapeutic Innovation, Early Detection, Prevention, and Interception.

Advances in targeted therapies, immunotherapy, and early detection have revolutionized lung cancer treatment and extended survival. Nonetheless, lung cancer remains highly fatal. Here, we identify knowledge gaps and propose critical areas of future research, aligning with the mission of the American Association for Cancer Research (AACR) Lung Cancer Task Force. We delineate research priorities, including advancing prevention initiatives, enhancing early detection strategies, developing novel treatments, and refining patient stratification. Addressing disparities and increasing efforts on relatively neglected lung cancer subtypes are also essential. Finally, international collaboration, centralized clinical trial databases, novel clinical trial designs, and artificial intelligence-driven analytics should accelerate precision medicine and aid in elucidating drug resistance mechanisms. Together, these efforts promise to improve patient outcomes.

SIGNIFICANCE: Despite substantial progress in understanding disease biology and improving therapy, lung cancer remains the leading cause of global cancer-related deaths. The members of the AACR Lung Cancer Task Force describe reas of unmet need and define near-term research priorities and opportunities to reduce lung cancer morbidity and mortality.

PMID: 42001483 [Indexed for MEDLINE]

26. Cancer Cell. 2026 Jun 18:S1535-6108(26)00265-5. doi: 10.1016/j.ccell.2026.05. 020.  

Targeting TROP2 in drug-tolerant persister cells delays EGFR tyrosine kinase inhibitor resistance in non-small-cell lung cancer.

Drug-tolerant persister (DTP) cells play a key role in the development of resistance to EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small-cell lung cancer (NSCLC). Through comprehensive analyses, we identify that TROP2 is dynamically upregulated during TKI-induced DTP formation and functionally contributes to DTP maintenance. Mechanistically, c-Myc acts as a transcriptional repressor of TROP2, and TKI-mediated MAPK pathway inhibition reduces c-Myc levels, leading to TROP2 upregulation. Importantly, combining the TROP2-targeting antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT) with osimertinib effectively suppresses DTP emergence and delays tumor relapse in preclinical models. An ongoing phase 2 trial evaluating first-line sac-TMT plus osimertinib combination therapy in patients with advanced EGFR-mutant NSCLC shows preliminary efficacy. Together, our findings establish TROP2 as a therapeutically actionable vulnerability in DTP cells and support the clinical development of TROP2-ADC combined with EGFR-TKI as a first-line strategy to delay TKI resistance and improve outcomes in EGFR-mutant NSCLC.

PMID: 42314664

27. Nat Immunol. 2026 Jun;27(6):1268-1281. doi: 10.1038/s41590-026-02515-5.

Epigenetic reprogramming of T cell metabolism restores function and enhances anti-tumor immunity in lung cancer.

T cell exhaustion represents a critical target for immunotherapy in cancer. Nevertheless, T cells exhibit diminished responsiveness to immune checkpoint inhibitors once they transition to a terminally exhausted state. Here we used an epigenetic drug screen and identified bromodomain and extra-terminal motif inhibitors (BETis) as enhancers of effector functions in primary exhausted T cells (TEX) from malignant pleural effusions in patients with lung cancer. Transcriptomics, metabolomics and ATAC-seq analyses revealed that BETis reinvigorate TEX cells by activating the polyamine biosynthesis pathway, expanding intracellular polyamine pools and altering chromatin accessibility. Genetic and pharmacological inhibition of ornithine decarboxylase (ODC1), a key enzyme in this pathway, abolished BETi-mediated immunopotentiation. Single-cell RNA-seq demonstrated that BETis reduced terminal TEX while promoting progenitor TEX through activation of the MYC-ODC axis. BETi treatment or adoptive transfer of BETi-treated T cells suppressed malignant pleural effusion formation in a syngeneic lung cancer model. These findings highlight an epigenetic-metabolic approach to enhance TEX plasticity and offer insights for novel cancer immunotherapies.

PMID: 42120791 [Indexed for MEDLINE]

28. J Clin Oncol. 2026 Jun 20;44(18):1670-1675. doi: 10.1200/JCO-26-00434.

Long-Term Efficacy and Safety of Taletrectinib in Patients With ROS1+ Non-Small Cell Lung Cancer: Results From the Phase II TRUST-I Study.

Taletrectinib is a next-generation, CNS-active, selective ROS1 tyrosine kinase inhibitor (TKI) with activity against the ROS1 G2032R resistance mutation. Initial data from the TRUST-I study (ClinicalTrials.gov identifier: NCT04395677) demonstrated high response rates and intracranial (IC) activity, with promising durability, in Chinese patients with advanced ROS1+ non-small cell lung cancer (NSCLC). With longer follow-up, taletrectinib continued to demonstrate high and durable response rates in both TKI-naïve and crizotinib-pretreated patients, including IC activity and promising overall survival (OS). Among 103 TKI-naïve patients who started taletrectinib at 600 mg once daily (median follow-up, 51.0 months), the objective response rate (ORR) was 90.3% (95% CI, 82.9 to 95.3), the median duration of response (DOR) and median progression-free survival (PFS) exceeded 4 years (49.7 months and 49.6 months, respectively), and median OS was not reached. Among 66 crizotinib-pretreated patients (median follow-up, 45.2 months), the ORR was 51.5%, the median DOR was 13.2 months, the median PFS was 7.6 months, and the median OS was 25.6 months. The safety profile remained consistent with prior reports, and no new safety signals were identified. Overall, taletrectinib demonstrated durable long-term efficacy and a manageable safety profile in patients with advanced ROS1+ NSCLC.

PMID: 42013573 [Indexed for MEDLINE]

29. Nat Rev Clin Oncol. 2026 Jun 30. doi: 10.1038/s41571-026-01174-7.

Improving neoadjuvant and perioperative therapy in non-small-cell lung cancer.

Neoadjuvant chemoimmunotherapy, comprising an anti-PD-(L)1 antibody and platinum-doublet chemotherapy, given alone or as part of a perioperative regimen with the addition of adjuvant anti-PD-(L)1 therapy, has become the standard of care for patients with early-stage, resectable non-oncogene-driven non-small-cell lung cancer (NSCLC). This approach has demonstrated substantial increases in pathological response rates and improvements in long-term outcomes, including overall survival. However, these advances have largely been achieved through uniform treatment application across biologically heterogeneous tumours. As a result, a central challenge in contemporary perioperative management is how to identify which patients require escalation or de-escalation of treatment following surgery and which individuals could safely avoid unnecessary treatment. In this Review, we summarize current evidence supporting pathological response, and particularly pathological complete response (pCR), as a robust and clinically meaningful surrogate for durable benefit in patients with NSCLC. We then consider how complementary tools, including circulating tumour DNA, radiomics and metabolic imaging approaches, and baseline molecular and immune biomarkers, can be integrated to refine patient selection and dynamically adapt perioperative strategies. Finally, we describe potential therapeutic strategies to intensify perioperative treatment in biologically high-risk populations, with the dual objective of increasing the likelihood of a pCR and improving disease control in patients with an insufficient pathological response.

PMID: 42380613

30. Adv Mater. 2026 Jun;38(31):e20216. doi: 10.1002/adma.202520216.

APE1-Triggered Inhalable Microsphere (ATIM) for In Situ Non-Small Cell Lung Cancer Theranostics.

Distinguishing benign from malignant pulmonary nodules remains a major clinical challenge, where misdiagnosis may lead to either delayed cancer treatment or unnecessary invasive procedures. Here, we report apurinic/apyrimidinic endonuclease 1 (APE1)-triggered inhalable microsphere (ATIM) for non-small cell lung cancer (NSCLC) theranostics by leveraging inhalation delivery and homotypic targeting to accelerate the local enrichment of DNA tetrahedrons (TDNs) in pulmonary tumors, which enables in situ NSCLC theranostics. Upon intracellular recognition of the APE1, entropy-driven catalytic circuits are activated, triggering nanoparticle aggregation to amplify fluorescence for real-time tumor imaging and releasing miR-126-3p to induce tumor cell apoptosis by suppressing ADAM9. In a mouse orthotopic NSCLC model, the tumor-bearing group showed a fluorescent intensity 1.67-fold higher than the healthy group, and the pulmonary accumulation of the ATIM system via inhalation was 3.12-fold higher than that via intravenous injection, while ATIM therapy significantly reduced the tumor burden to a relative area of 45.3 ± 1.6%. Our results demonstrate that ATIM achieves accurate discrimination between benign and malignant pulmonary nodules while effectively inducing apoptosis in tumor cells. This theranostic system offers a promising dual-functional platform for precision diagnosis and targeted therapy in early-stage NSCLC.

PMID: 42051030 [Indexed for MEDLINE]

31. J Clin Oncol. 2026 Jun;44(16):1540-1552. doi: 10.1200/JCO-25-01958.

Metastatic Trajectories in Non-Small Cell Lung Cancer Guide Local and Systemic Therapies.

Advances in systemic therapy have improved outcomes for metastatic non-small cell lung cancer (NSCLC), yet resistance and progression remain nearly universal. Local therapies such as radiotherapy, surgery, and image-guided ablation can extend disease control in selected patients, but existing classifications-including dynamic models of oligometastatic disease-assign a single state per patient and do not capture lesion-level heterogeneity. We introduce the concept of metastatic trajectories-the spatiotemporal dynamics of response and progression across lesions, organs, and patients-as a framework to characterize intrapatient heterogeneity and inform adaptive treatment strategies. Dimensions of metastatic trajectories include the magnitude and homogeneity of response, mechanisms of resistance, organotropism, and the pattern, site, extent, and pace of progression. This framework shifts the focus from overall disease states to individual lesion behavior over time, enabling reactive strategies based on observed trajectories and anticipatory strategies based on predicted ones. We review the biological foundations of intrapatient heterogeneity-including genomic diversification, nongenetic plasticity, and tumor-microenvironmental adaptation-that drive divergent lesion evolution and treatment response. Emerging biomarkers such as circulating tumor DNA and radiomic signatures, together with integrative genomic and functional imaging approaches, may allow tracking and prediction of trajectory evolution. Standardized reporting parameters are proposed to ensure consistent documentation and facilitate validation across studies. Integrating trajectory-based assessment into clinical practice could refine patient selection for local and systemic therapy, enable biology-informed adaptation of treatment timing and intensity, and provide a foundation for next-generation clinical trials aimed at precision management of metastatic NSCLC.

PMID: 42085620 [Indexed for MEDLINE]

32. Cancer Discov. 2026 Jun 1;16(6):1074-1086. doi: 10.1158/2159-8290.CD-25-0960.

ELIOS: A Multicenter, Molecular Profiling Study of Patients with EGFR-Mutant Advanced Non-Small Cell Lung Cancer Treated with First-Line Osimertinib.

ELIOS (NCT03239340) prospectively compared tumor biopsies obtained pre-treatment and post-progression to characterize acquired resistance mechanisms to first-line osimertinib in epidermal growth factor receptor (EGFR)-mutant advanced non-small cell lung cancer (NSCLC). Of 154 patients enrolled, 52 patients had next-generation sequencing (NGS) results from paired tissue biopsies. The most common acquired alterations at progression were MET amplification (17%), deletion of CDKN2A/CDKN2B (15%) and MTAP (13%), and EGFR C797S (13%). Proteogenomic analysis (n = 32 at baseline and n = 18 post-progression) showed TROP2 was highly expressed at baseline and post-progression, irrespective of genetic alterations observed. In a separate analysis of patients with matched tissue and plasma samples post-progression (n = 51), 82% had potential resistance alterations by NGS, demonstrating the complementary roles of tissue and plasma NGS. These results highlight the challenges of obtaining tissue biopsies in patients with NSCLC progressing on targeted therapy, the potential for heterogeneous resistance, and the need for broad-acting treatment strategies.

SIGNIFICANCE: ELIOS confirmed acquired resistance mechanisms to first-line osimertinib in a prospective, molecular profiling study of paired pre- and post-treatment tissue samples and provided the first proteogenomic characterization before/after osimertinib, identifying novel proteomic markers. ELIOS showed the potential for heterogeneous resistance, highlighting that strategies targeting multiple resistance pathways may be required.

PMID: 41790042 [Indexed for MEDLINE]

33. JAMA Oncol. 2026 Jun 4:e261645. doi: 10.1001/jamaoncol.2026.1645.

First-Line Serplulimab in Extensive-Stage Small Cell Lung Cancer: Secondary Analysis of the ASTRUM-005 Phase 3 Randomized Clinical Trial.

IMPORTANCE: The ASTRUM-005 phase 3 randomized clinical trial showed substantial survival benefit from adding serplulimab to chemotherapy for previously untreated extensive-stage small cell lung cancer (ES-SCLC). However, the long-term outcomes are unclear.

OBJECTIVE: To investigate the efficacy, safety, patient-reported outcomes (PROs), and exploratory biomarker findings from ASTRUM-005 at an extended follow-up.

DESIGN, SETTING, AND PARTICIPANTS: This international, double-blind, phase 3 randomized clinical trial enrolled patients from September 12, 2019, to April 27, 2021 in China, Russia, Ukraine, Poland, Turkey, and Georgia. Eligible patients had histologically or cytologically confirmed ES-SCLC with no prior systemic therapy. Patients were followed up through May 7, 2024, and the data analysis of this prespecified, secondary analysis lasted from August to September 2024. The median follow-up duration was 42.4 months (range, 0.2-55.2).

EXPOSURES: Patients were randomized in a 2:1 ratio to receive intravenous serplulimab (4.5 mg/kg; serplulimab group) or placebo (placebo group), which was combined with up to 4 cycles of carboplatin and etoposide every 3 weeks.

MAIN OUTCOMES AND MEASURES: The primary end point was overall survival (OS). Secondary end points included other efficacy end points, safety, and PROs.

RESULTS: A total of 585 patients (median [range] age was 63 [28-76] years in the serplulimab group and 62 [31-83] years in the placebo group) with previously untreated ES-SCLC, and 389 (66.5%) were randomly assigned to the serplulimab group and 196 (33.5%) to the placebo group. Baseline characteristics were balanced across treatment groups. At data cutoff, 280 OS events (72.0%) in the serplulimab group and 166 (84.7%) in the placebo group were observed. Compared with the placebo group, the serplulimab group showed more favorable efficacy (median OS, 15.8 [95% CI, 13.9-17.4] vs 11.1 [95% CI, 10.0-12.4] months; hazard ratio, 0.60; 95% CI, 0.49-0.73; P < .001). The serplulimab group showed improved OS rates at 4 years compared with the placebo group (21.9% vs 7.2%). Grade 3 or higher serplulimab-related or placebo-related treatment-emergent adverse events occurred for 136 (35.0%) and 57 patients (29.1%) in the respective groups. A PRO analysis revealed consistent trends of improved overall health, dyspnea, and pain in both groups and faster recovery from alopecia in the serplulimab group.

CONCLUSIONS AND RELEVANCE: This secondary analysis of a randomized clinical trial demonstrated long-term benefit from adding serplulimab to chemotherapy for previously untreated patients with ES-SCLC, supporting this therapy as a first-line standard of care for this patient population.

PMID: 42240984

34. Lancet Oncol. 2026 Jul;27(7):785-794. doi: 10.1016/S1470-2045(26)00090-2.

Aumolertinib with or without chemotherapy in EGFR-mutated advanced non-small-cell lung cancer (AENEAS2): an open-label, multicentre, randomized, controlled, phase 3 trial.

BACKGROUND: Although third-generation epidermal growth-factor receptor (EGFR)-tyrosine-kinase inhibitors (TKIs) are standard first-line therapies for patients with advanced EGFR-mutated non-small-cell lung cancer (NSCLC), their effectiveness is often limited by the emergence of drug resistance and subsequent disease progression. Given the previously established clinical efficacy and adverse event profile of aumolertinib, we aimed to evaluate the efficacy and adverse event profile of aumolertinib in combination with platinum-based chemotherapy versus aumolertinib monotherapy as first-line treatment for patients with locally advanced or metastatic NSCLC patients with EGFR-sensitive mutations.

METHODS: The open-label, multicentre, randomized, controlled, phase 3 AENEAS2 trial was done across 60 hospitals in China. Patients aged at least 18 years with Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1; treatment-naive; histologically or cytologically confirmed locally advanced or metastatic NSCLC harbouring EGFR-sensitive mutations (ex19del/L858R with or without other EGFR mutations) were eligible. Brain metastases were allowed if neurologically stable. Previous EGFR-TKI therapy was an exclusion criterion. Patients were randomly assigned (1:1) with block randomisation (block size of 6), stratified by EGFR mutation type and baseline brain metastasis, to receive aumolertinib monotherapy (110 mg orally once a day) or combination therapy (aumolertinib 110 mg orally once a day plus pemetrexed 500 mg/m2 intravenously with cisplatin [75 mg/m2] or carboplatin [area under the plasma concentration-time curve 5] intravenously on day 1 of 21-day cycles for 4-6 cycles), followed by maintenance therapy (aumolertinib 110 mg orally once a day and pemetrexed 500 mg/m2 intravenously once every 3 weeks). The primary endpoint was progression-free survival assessed by blinded independent central review (BICR; RECIST version 1.1). Efficacy was analysed in the full-analysis set, which included all randomly assigned patients, and safety was analysed in patients who received at least one dose of the actual trial treatment. The trial is registered at ClinicalTrials.gov, NCT04923906, and is ongoing, but closed to enrolment.

FINDINGS: Between Aug 4, 2021, to June 18, 2024, of 1011 patients assessed for eligibility, 624 randomly assigned patients (median age 59·0 years [IQR 52·0-66·0]; 337 [54%] were female, 287 [46%] were male) were randomly assigned. 310 (50%) patients received combination therapy and 314 (50%) received monotherapy. As of the data cutoff date (June 18, 2024), the median follow-up was 23·4 months (IQR 20·5-26·5), In the full-analysis set, median BICR-assessed progression-free survival was 28·9 months (95% CI 26.3, NA) in the combination therapy versus 18·9 months (17·8-21·1) in the monotherapy (hazard ratio [HR] 0·47, 95% CI 0·37-0·60; log-rank p<0·0001). The most common grade 3-4 adverse events (occurring in at least 20% in any group) were neutrophil count decreased (168 [55%] of 304 in the combination group versus four [1%] of 316 in monotherapy group), white blood cell count decreased (103 [34%] vs one [<1%]), and platelet count decreased (62 [20%] vs two [1%]). Serious adverse events occurred in 109 (36%) patients in the combination group and 53 (17%) in the monotherapy group, the most common of which were platelet count decreased (22 [7%] vs 0), neutrophil count decreased (17 [6%] vs 0), white blood cell count decreased (13 [4%] vs 0), and anaemia (ten [3%] vs two [1%]). Treatment-related deaths occurred in one (<1%) patient in the combination group (encephalopathy) and two (1%) in the monotherapy group (pulmonary embolism and respiratory failure with circulatory collapse).

INTERPRETATION: Aumolertinib in combination with chemotherapy significantly improved progression-free survival. Although this regimen was associated with increased toxicity, the side-effects were managed with dose adjustment and supportive treatment aligned with clinical practice. Long-term follow-up is required to assess overall survival. The AENEAS2 study provides evidence to guide clinical practice regarding EGFR-TKIs and their combination use in treating patients with advanced EGFR-mutated NSCLC.

FUNDING: Jiangsu Hansoh Pharmaceutical Group, and the Collaborative Innovation Center for Clinical and Translational Science by Ministry of Education & Shanghai.

PMID: 42296979 [Indexed for MEDLINE]

35. JAMA. 2026 Jun 17:e267745. doi: 10.1001/jama.2026.7745. Online ahead of print.

Bispecific Antibody Ivonescimab Added to Chemotherapy in EGFR-Variant NonSmall

Cell Lung Cancer: The HARMONi-A Randomized Clinical Trial.

IMPORTANCE: Patients with epidermal growth factor receptor (EGFR) gene variant nonsquamous non-small cell lung cancer (NSCLC) who have disease progression after prior EGFR tyrosine kinase inhibitor (TKI) therapy have limited treatment options, creating a need for more effective subsequent therapies.

OBJECTIVE: To provide final overall results of a trial assessing whether adding ivonescimab (a bispecific antibody targeting programmed cell death protein 1 and vascular endothelial growth factor) to chemotherapy improves overall survival in this population.

DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled phase 3 trial conducted at 55 sites in China. From January 25 to November 2, 2022, a total of 322 adult patients with locally advanced or metastatic EGFR-variant nonsquamous NSCLC who had received prior EGFR-TKI therapy were enrolled. The data cutoff date was April 12, 2025.

INTERVENTIONS: Patients were randomized 1:1 to receive ivonescimab (20 mg/kg; n = 161) or placebo (n = 161) plus chemotherapy with pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy.

MAIN OUTCOMES AND MEASURES: This final results report focuses on overall survival, the key secondary end point, tested in a hierarchical manner (the primary end point was progression-free survival assessed by an independent radiology review committee).

RESULTS: The 322 enrolled patients had a median age of 59.4 years, and 51.6% were female. During a median follow-up of 32.5 months, ivonescimab plus chemotherapy improved overall survival compared with chemotherapy alone (median survival, 16.8 months vs 14.1 months; stratified hazard ratio, 0.74; 95% CI, 0.58-0.95; P = .02). The absolute difference in median overall survival was 2.7 months. Estimated 30-month survival rates were 29.1% (95% CI, 22.1%-36.4%) with ivonescimab and 18.4% (95% CI, 12.8%-24.8%) with placebo. Grade 3 or higher treatment-emergent adverse events occurred in 67.1% and 54.7% of patients receiving ivonescimab and placebo, respectively.

CONCLUSIONS AND RELEVANCE: Ivonescimab plus chemotherapy provided a statistically significant and clinically meaningful improvement in overall survival with an acceptable safety profile in patients with EGFR-variant NSCLC after EGFR-TKI therapy.

PMID: 42307937