Non-Small Cell Lung Cancer
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Jun 01 – Jun 08, 2026
Robust Findings for HER2 TKI in NSCLC.
CANCER DISCOV · Q1 JOURNAL - RANK #10/326TOP-TIER
This study evaluates the clinical efficacy of zongertinib, a HER2 tyrosine kinase inhibitor (TKI), in treating HER2-mutant non-small cell lung cancer (NSCLC). Among 74 patients who received a daily dose, the objective response rate was 76%, and the median progression-free survival was 14.4 months, significantly outperforming traditional chemotherapy response rates of approximately 30% and a median duration of under 7 months. The findings suggest that zongertinib offers a notable improvement compared to the standard treatment options. These results highlight the potential of targeted therapies in advancing the treatment landscape for HER2-mutant NSCLC patients.
10.1158/2159-8290.CD-NW2026-0051
Adjuvant Nivolumab vs Observation in Resected Non-Small Cell Lung Cancer: A Randomized Clinical Trial.
JAMA-J AM MED ASSOC · Q1 JOURNAL - RANK #4/332TOP-TIER
This open-label, randomized phase 3 clinical trial evaluated adjuvant nivolumab versus observation in 935 patients with resected non-small cell lung cancer (NSCLC) following planned adjuvant therapy. Patients were randomized 1:1 to receive nivolumab 480 mg intravenously every 4 weeks for up to 1 year or standard observation, with co-primary endpoints of disease-free survival (DFS) in the intention-to-treat population and in those with PD-L1 ≥50%. After median 72.6 months follow-up, median DFS was 71.3 months with nivolumab vs 68.8 months with observation (HR 0.97; 95% CI 0.81-1.17; p=0.39), and in the PD-L1 ≥50% subset, 89.8 vs 78.5 months (HR 0.86; 95% CI 0.59-1.25; p=0.22). The authors concluded adjuvant nivolumab did not improve DFS in this patient population.
10.1001/jama.2026.8992
Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in advanced squamous non-small-cell lung cancer (HARMONi-6): interim overall survival analysis of a randomised, double-blind, phase 3 trial in China.
LANCET · Q1 JOURNAL - RANK #1/332TOP-TIER
HARMONi-6 is a randomized, double-blind, phase 3 trial at 50 Chinese hospitals comparing ivonescimab plus paclitaxel/carboplatin (four cycles) followed by ivonescimab maintenance versus tislelizumab plus the same chemotherapy and tislelizumab maintenance in previously untreated advanced squamous NSCLC. 532 patients were randomized (266/266), median age 64 (IQR 59–69), 93% male; the prespecified interim overall survival analysis was conducted after 204 deaths with a median follow-up of 21.4 months. Ivonescimab improved median overall survival to 27.9 months (95% CI 27.89–NE) versus 23.7 months (20.11–NE) with tislelizumab (HR 0.66, 95% CI 0.50–0.87; p=0.0017), with grade ≥3 treatment-related adverse events in 69% vs 59% and grade ≥3 hemorrhage in 3% vs 1%. Investigators concluded ivonescimab plus chemotherapy confers a statistically significant and clinically meaningful overall survival benefit as first-line therapy in advanced squamous NSCLC.
10.1016/S0140-6736(26)00966-9
May 25 – Jun 01, 2026
Lorlatinib versus crizotinib as first-line treatment for advanced ALK-positive non-small cell lung cancer: 7-year update from the phase 3 CROWN study.
ANN ONCOL · Q1 JOURNAL - RANK #4/326TOP-TIER
The study aimed to evaluate the long-term efficacy and safety of lorlatinib versus crizotinib as first-line treatment for advanced ALK-positive non-small cell lung cancer (NSCLC) over 7 years in the phase 3 CROWN trial. A total of 296 treatment-naive patients were randomized 1:1 to receive lorlatinib (100 mg OD) or crizotinib (250 mg BID), with investigator-assessed outcomes including progression-free survival (PFS), safety, and biomarker analyses. At median follow-ups of 83.0 and 77.2 months, median PFS was not reached (NR; 68.5-NR) for lorlatinib versus 9.1 months (7.4-10.9) for crizotinib (HR 0.19; 95% CI 0.13-0.26), with 7-year PFS rates of 55% and 3%, respectively. The safety profile remained consistent with prior findings, and lorlatinib demonstrated sustained long-term disease control, suggesting potential for advanced ALK-positive NSCLC to become a chronic condition.
10.1016/j.annonc.2026.05.692
First-line envafolimab plus recombinant human-endostatin in advanced non-small cell lung cancer with PD-L1 tumor proportion score ≥1% (Endouble): A multicenter, prospective, single-arm, phase 2 trial.
CANCER-AM CANCER SOC · Q1 JOURNAL - RANK #68/326
This multicenter, prospective, single-arm, phase 2 trial evaluated the efficacy and safety of envafolimab plus recombinant human endostatin (Rh-endostatin) in 33 treatment-naive advanced NSCLC patients with PD-L1-positive and no driver gene mutations. Patients received treatment every 21 days until disease progression or intolerable toxicity, with primary endpoints being objective response rate (ORR) and safety, and secondary endpoints including progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and duration of response (DOR). The ORR was 48.5% (95% CI, 30.8%-66.5%), DCR was 81.8% (95% CI, 64.5%-93.0%), median PFS was 12.3 months (95% CI, 3.1-21.5 months), and 1-year OS rate was 73.9%, with no grade 4 or 5 adverse events reported. The study concluded that the combination demonstrated favorable efficacy and tolerable toxicity in this patient population, supported by exploratory biomarker analysis showing AUC values of 0.77 for MMP1 and 0.68 for TNFRSF6B.
10.1002/cncr.70479
Sacituzumab tirumotecan plus pembrolizumab versus pembrolizumab in PD-L1-positive advanced non-small-cell lung cancer (OptiTROP-Lung05): interim analysis of a randomised, open-label, phase 3 trial.
LANCET · Q1 JOURNAL - RANK #1/332TOP-TIER
The study evaluated the efficacy and safety of sacituzumab tirumotecan (sac-TMT) plus pembrolizumab versus pembrolizumab alone as first-line treatment for PD-L1-positive advanced non-small-cell lung cancer (NSCLC) in a randomized, open-label, phase 3 trial. A total of 413 patients were assigned to sac-TMT plus pembrolizumab (n=208) or pembrolizumab alone (n=205), with a median follow-up of 10.5 months. The combination therapy significantly improved progression-free survival (not reached vs 5.7 months; HR 0.35, 95% CI 0.26-0.47, p<0.0001) and showed consistent benefits across PD-L1 subgroups, though with higher grade 3+ adverse events (55% vs 31%). The study concludes that sac-TMT plus pembrolizumab may redefine first-line treatment for this patient population.
10.1016/S0140-6736(26)00968-2
Efficacy and safety of subcutaneous and intravenous administration of atezolizumab in patients with non-small cell lung cancer, including early-stage, locally advanced or metastatic disease: Updated results of the IMscin001 and IMscin002 randomized studies.
LUNG CANCER · Q1 JOURNAL - RANK #19/108
These two randomized, prospective clinical trials (IMscin001 and IMscin002) evaluated the efficacy, safety, and immunogenicity of subcutaneous (SC) versus intravenous (IV) atezolizumab in patients with non-small cell lung cancer (NSCLC) across early-stage, locally advanced, or metastatic settings. Patients were randomized to receive either SC or IV atezolizumab every three weeks, with IMscin002 including a crossover and continuation period. Updated results show similar overall survival between groups in IMscin001 (median OS: 10.9 vs 10.1 months; hazard ratio: 1.00, 95% CI: 0.78-1.27) and 44.7% ongoing clinical benefit after cycle 16 in IMscin002. Both studies found comparable safety profiles, immunogenicity (20.0-21.1% anti-drug antibodies), and no new safety signals.
10.1016/j.lungcan.2026.109452
Early radiological response pattern predicts long-term response in patients with non-small cell lung cancer treated with immune-checkpoint inhibitors.
CANCER IMAGING · Q1 JOURNAL - RANK #40/212
This prospective study evaluated early radiological response patterns in 122 NSCLC patients treated with immune checkpoint inhibitors (ICIs) from 2019 to 2023. Imaging per iRECIST assessed early sum-of-diameters (SoD) change at 8–12 weeks. Key findings: 32.8% achieved best overall response, 47.5% durable clinical benefit (DCB); early SoD reduction predicted DCB (AUC 0.764, p>0.05) and BOR (AUC 0.701, p<0.01). The authors conclude early radiological dynamics robustly predict outcomes and outperform laboratory biomarkers.
10.1186/s40644-026-01048-2
Mature Outcomes and Patterns of Failure in the Phase II FLARE-RT Trial of Biological Image-guided and Risk-Adaptive Chemoradiation for Unresectable NSCLC.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This Phase II FLARE-RT trial evaluated the efficacy of biological image-guided and risk-adaptive chemoradiation in 49 patients with unresectable NSCLC. Participants were stratified based on FDG-PET response, receiving either 60Gy or intensified doses between 74-90Gy. After a 52.3-month median follow-up, 1- and 2-year OS rates were reported as 81.6% and 54.2%, respectively, with 1- and 2-year PFS rates of 53.1% and 40.5%. The study demonstrated durable locoregional control, identified FDG-PET metrics as predictors of progression, and highlighted a potential benefit of adjunct durvalumab in reducing distant metastases without compromising local control, supporting its use in biomarker-guided NSCLC therapy.
10.1158/1078-0432.CCR-25-2626
Intrathecal Allogeneic B7-H3-targeted CAR γδ T Cells for Leptomeningeal Metastasis from Solid Tumors: Safety, Efficacy, and Immunological Dynamics in a Phase 1 Trial.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
Phase 1 trial NCT06592092 evaluated intrathecal QH104, an allogeneic B7-H3–targeted CAR γδ T-cell therapy, in three patients with B7-H3–positive leptomeningeal metastases from lung adenocarcinoma (n=2) or triple-negative breast cancer (n=1). Patients received 3 × 10^7 cells per infusion via lumbar puncture or Ommaya reservoir; primary endpoint was clinical response, with safety, overall survival, quality of life, and PK/PD as secondary endpoints. QH104 was generally well tolerated (no grade ≥4 TRAEs; one grade 3 ICANS resolving with care), all patients achieved stable disease at days 14 and 30 with symptom improvement in two, and CSF cytology converted and remained negative to day 30 in one baseline-positive case. CAR γδ T cells persisted in CSF for at least one week with increased IFN-γ, and single-cell sequencing indicated IFN-γ–associated immune remodeling.
10.1158/1078-0432.CCR-26-0738
Osimertinib plus selumetinib in patients with EGFR-mutated advanced NSCLC with BRAF alterations post-progression on first-line osimertinib: ORCHARD.
EUR J CANCER · Q1 JOURNAL - RANK #45/326
The ORCHARD study was a phase II, biomarker-matched, prospective clinical trial evaluating osimertinib plus selumetinib in 16 patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) with BRAF alterations after progression on first-line osimertinib. Patients received osimertinib (80 mg daily) and selumetinib (75 mg twice daily) until disease progression or intolerable toxicity, with primary and secondary endpoints including objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. The ORR was 7% (80% CI < 1-25), median PFS was 3.4 months (95% CI 1.3-5.4), median OS was 14.0 months (95% CI 6.2-not calculable), and 69% experienced grade ≥3 adverse events. The combination showed minimal efficacy and a safety profile consistent with known drug effects, concluding further evaluation is not warranted.
10.1016/j.ejca.2026.116807
Sequential chemo-immunotherapy followed by standard versus reduced thoracic radiotherapy for older and/or frail stage III non-small-cell lung cancer: A randomized open-label cohort trial.
PLOS MED · Q1 JOURNAL - RANK #13/332
This phase II randomized, open-label, two-cohort trial evaluated sequential chemo-immunotherapy followed by standard versus reduced thoracic radiotherapy (RT) intensity in 56 older and/or frail patients with stage III NSCLC ineligible for concurrent chemoradiotherapy (cCRT). The 1-year progression-free survival (PFS) was 84.3% for the standard RT group and 70.7% for the reduced RT group in the intention-to-treat set. Grade 3/4 adverse events occurred in 71.4% of standard RT patients and 53.6% of reduced RT patients, with grade 5 AEs in 10.7% and 3.6%, respectively. The results indicate that reduced RT combined with sequential chemo-immunotherapy is a feasible option, though limitations such as small sample size and non-comparative design necessitate further randomized trials.
10.1371/journal.pmed.1005111
Amivantamab plus chemotherapy vs. chemotherapy as first-line treatment in Chinese mainland patients with EGFR exon 20 insertion non-small cell lung cancer: Subgroup analysis of the randomized PAPILLON trial.
CHINESE MED J-PEKING · Q1 JOURNAL - RANK #23/332
This subgroup analysis of the phase 3 PAPILLON trial assessed amivantamab with carboplatin-pemetrexed versus carboplatin-pemetrexed alone in treatment-naïve Chinese mainland patients with advanced EGFR exon 20 insertion non-small cell lung cancer. In this randomized, open-label study, 87 patients were allocated to amivantamab plus chemotherapy (n = 39) or chemotherapy (n = 48); progression-free survival (PFS) by blinded independent central review was the primary endpoint. Median PFS was 12.3 months (95% CI 7.0-NE) with the combination versus 6.7 months (95% CI 4.2-8.6) with chemotherapy (HR 0.47, 95% CI 0.26-0.85, p = 0.0109); objective response rates were 71.8% vs 48.9% (OR 2.46, 95% CI 1.01-5.98). No new safety signals emerged and no patients discontinued amivantamab for toxicity, supporting the regimen as a first-line option for this molecularly defined NSCLC population.
10.1097/CM9.0000000000004134
May 18 – May 25, 2026
Association between patient-reported outcomes and pathological response in neoadjuvant chemoimmunotherapy-a post hoc analysis of the TD-FOREKNOW trial.
TRANSL LUNG CANCER R · Q1 JOURNAL - RANK #26/108
This post hoc analysis of the randomized phase 2 TD-FOREKNOW trial examined whether pathologic complete response (pCR) correlates with patient-reported outcomes (PROs) in stage IIIA–IIIB NSCLC treated with neoadjuvant camrelizumab plus chemotherapy or chemotherapy alone followed by surgery. Among 94 randomized patients, PRO analyses focused on 40 who received camrelizumab plus chemotherapy and completed ≥1 PRO assessment (14 pCR; 26 non-pCR), using change-from-baseline comparisons of global health status/quality of life, cough, dyspnea, and hemoptysis. GHS/QoL declined during neoadjuvant therapy and recovered postoperatively in both groups; pCR patients had greater improvements during treatment in cough (LS mean difference −18.2; 95% CI −33.0 to −3.5; P=0.02) and dyspnea (−21.3; 95% CI −38.3 to −4.3; P=0.02) versus non-pCR. The study concludes pCR is associated with superior PROs, suggesting pCR may reflect patient-centered benefits beyond survival.
10.21037/tlcr-2025-1-1425
Long-term outcomes after proton therapy vs. intensity-modulated photon radiotherapy with concurrent chemotherapy for locally advanced non-small-cell lung cancer: post-hoc analysis of a prospective randomized trial.
INT J RADIAT ONCOL · Q1 JOURNAL - RANK #14/212
This prospective randomized trial investigated the long-term effects of passive-scattering proton therapy (PSPT) versus intensity-modulated photon radiotherapy (IMRT) with concurrent chemotherapy for locally advanced non-small-cell lung cancer (NSCLC). Researchers measured toxicity, local failure, and survival, including radiation pneumonitis (10.9% IMRT vs 10.5% PSPT), esophageal toxicity, and major adverse cardiac events (MACE). PSPT led to fewer radiation-related MACEs, likely related to reduced coronary artery doses, while no differences were seen in local failure or progression-free survival. Overall survival was comparable to the RTOG 0617 trial among similar-stage NSCLC patients with good performance status.
10.1016/j.ijrobp.2026.05.012
Cadonilimab induction and consolidation for unresectable stage III non-small cell lung cancer patients receiving concurrent chemoradiation: safety run-in results of a prospective, phase II trial.
TRANSL LUNG CANCER R · Q1 JOURNAL - RANK #26/108
This prospective, single-arm phase II trial evaluated cadonilimab, a bispecific PD-1/CTLA-4 antibody, given as two cycles of induction with chemotherapy, followed by concurrent chemoradiotherapy and up to 1 year of cadonilimab consolidation in 20 patients with unresectable, driver-mutation-negative stage III NSCLC. Safety was the primary focus of this pre-specified run-in; dose-limiting toxicity (DLT) was defined as ≥grade 3 non-hematologic events lasting >7 days, any grade 4 non-hematologic event, or grade 5 potential treatment-related event within 90 days after cCRT. After a median 8.4 month follow-up, 19/20 completed cCRT and 17/20 began consolidation; 4 patients (20 %) experienced DLTs (pneumonitis 2, colitis 1, grade 5 pneumonia 1), while all patients experienced TRAEs, with grade 3–4 non-hematologic TRAEs in 50 %. The manageable safety profile supports ongoing enrollment to further evaluate efficacy and long-term outcomes of cadonilimab with cCRT in stage III NSCLC.
10.21037/tlcr-2026-1-0122
Pembrolizumab with or without chemotherapy among older adults with advanced lung adenocarcinoma: a national, nonrandomized open-label phase II trial (Alliance A171901).
JNCI-J NATL CANCER I · Q1 JOURNAL - RANK #44/326
This multicenter, nonrandomized open-label phase II trial (Alliance A171901; NCT04533451) evaluated first-line pembrolizumab with or without carboplatin/pemetrexed in adults aged ≥70 years with stage IV or recurrent lung adenocarcinoma, with the primary endpoint being the 6-month rate of solicited grade ≥3 adverse events and secondary endpoints including overall survival and quality of life. Among 95 evaluable patients (43 monotherapy; 52 combination; median age 77; 11.6% ECOG ≥2), grade ≥3 adverse events within 6 months occurred in 25.6% (95% CI 13.5–41.2) with monotherapy and 42.3% (95% CI 28.7–56.8) with combination therapy. Median overall survival was 16.4 months (95% CI 10.1–not estimable) versus 29.9 months (95% CI 16.4–not estimable), quality of life worsened during treatment, and a geriatric toxicity risk score did not predict severe AEs. The authors conclude AE rates are comparable to prior registration trials and support inclusion of older adults in future trials.
10.1093/jnci/djag157
Phase Ib of repotrectinib plus osimertinib in patients with EGFR-mutated advanced non-small cell lung cancer.
LUNG CANCER · Q1 JOURNAL - RANK #19/108
TOTEM (NCT04772235) was a phase Ib, prospective clinical trial evaluating repotrectinib plus osimertinib in EGFR-mutated advanced NSCLC resistant to prior therapies, using 3+3 dose-escalation (osimertinib 80 mg QD plus repotrectinib 80 mg QD, 160 mg QD, or 160 mg BID) followed by dose expansion post-osimertinib or post-osimertinib+chemotherapy. Thirty-one patients were enrolled (Feb 2022–Jan 2025); the recommended phase 2 dose was osimertinib 80 mg QD plus repotrectinib 160 mg BID. Grade 3–4 treatment-related adverse events occurred in 45.2%, most commonly dizziness (16.1%) and anemia (12.9%); ORR was 22.2% (95% CI 8.6–42.3) with six confirmed partial responses and a DoR of 6.9 months (95% CI 2.7–13.1), and median PFS was 4.0 months (95% CI 2.8–9.7). In patients with intracranial disease, icORR was 33.3% (95% CI 7.5–70.1) and median icPFS was 4.4 months (95% CI 2.7–NR), supporting further investigation.
10.1016/j.lungcan.2026.109461
May 11 – May 18, 2026
Phase I trial of CJRB-101 plus pembrolizumab in patients with metastatic non-small cell lung cancer, head and neck squamous cell carcinoma and melanoma.
J IMMUNOTHER CANCER · Q1 JOURNAL - RANK #12/183TOP-TIER
This first-in-human, two-part, phase I trial evaluated CJRB-101 (1×10 or 4×10 CFU/day) plus pembrolizumab (200 mg Q3W) in 42 patients with advanced NSCLC, melanoma, or HNSCC in ICI-naïve and ICI-refractory settings. In preclinical PDX models, CJRB-101 plus pembrolizumab showed enhanced tumor growth inhibition (TGI) of 61.9% versus 77.3% with CJRB-101 alone, alongside M2-to-M1 repolarization and cytotoxic T-cell activation. None of the patients experienced dose-limiting toxicities, and in ICI-naïve NSCLC with PD-L1 >50% (n=12), the overall response rate reached 58%, disease control was 75%, and the median progression-free survival was 9 months. The combination was well-tolerated, including in ICI-refractory cases with ORR of 5% and DCR of 41%, supporting further investigation of CJRB-101 plus pembrolizumab in advanced solid tumors.
10.1136/jitc-2025-014702
Simultaneous concurrent chemoradiation and SBRT in stage III NSCLC: Safety report of the phase I hybrid trial.
RADIOTHER ONCOL · Q1 JOURNAL - RANK #22/212
This phase I Hybrid trial prospectively enrolled 15 stage III NSCLC patients with peripheral primary tumors to assess safety of concurrent chemoradiation combining SBRT to the primary tumor and fractionated radiotherapy to lymph nodes with daily cisplatin. The hybrid schedule delivered 24 fractions of conventionally fractionated radiotherapy and 3 fractions of SBRT, with SBRT dose escalated between 14-18 Gy per fraction using TITE-CRM based on mean lung dose. No dose-limiting toxicity occurred at a maximum MLD of 19.1 Gy; grade 1-2 pneumonitis (N=7) and rib fractures (N=6) were common, with no G3+ pulmonary/mediastinal toxicities. Loco-regional control was 93%, but 73% developed distant metastasis at median 11 months, concluding the regimen is feasible and safe with high loco-regional control.
10.1016/j.radonc.2026.111551
Nivolumab plus chemoradiotherapy followed by nivolumab with or without ipilimumab for untreated locally advanced stage III NSCLC: a randomized phase 3 trial.
NAT CANCER · Q1 JOURNAL - RANK #11/326TOP-TIER
This randomized phase 3 trial (NCT04026412) tested nivolumab plus concurrent chemoradiotherapy (CCRT) followed by consolidation nivolumab+ipilimumab (arm A) or nivolumab alone (arm B) versus standard CCRT followed by durvalumab (arm C) in adults with untreated, unresectable stage III NSCLC. The primary endpoint was progression-free survival (PFS) for arm A versus arm C; secondary endpoints included overall survival (OS), PFS for arm B versus arm C, response rates, and safety, with a median follow-up of 30.5 months. Arm A did not improve PFS versus durvalumab (HR 0.95, 96% CI 0.77–1.19; P=0.65) and showed no OS benefit (HR 1.12, 95% CI 0.87–1.43); nivolumab alone also did not improve PFS (HR 0.84, 95% CI 0.69–1.04) or OS (HR 0.97, 95% CI 0.76–1.24). Pneumonitis was increased with nivolumab-containing regimens, underscoring the need for more effective approaches.
10.1038/s43018-026-01161-y
Novel multiplex immunofluorescence-based tumor inflammation score provides apparent predictive biomarker in a phase I/II study of pembrolizumab with gemcitabine in patients with previously-treated advanced non-small cell lung cancer (NSCLC).
ONCOIMMUNOLOGY · Q1 JOURNAL - RANK #51/326
The study evaluates the safety and potential efficacy of combining pembrolizumab with gemcitabine in a phase I/II clinical trial involving 16 immunotherapy-naïve patients with previously treated advanced non-small cell lung cancer (NSCLC). The findings suggest the combination is safe but lacks synergistic efficacy compared to historical controls. A novel tumor inflammation score, based on Treg/CD3 T-cell proximity and overall T-cell density, was associated with treatment outcomes (p < 0.002), highlighting a potential biomarker for response. Additionally, elevated autoantibody responses to tumor antigens trended toward worse outcomes (p = 0.06), suggesting immune escape mechanisms in tumors with high autoantibody levels.
10.1080/2162402X.2026.2661444
Final overall survival analysis of the APPLE study: atezolizumab and platinum-pemetrexed with or without bevacizumab for metastatic nonsquamous non-small cell lung cancer.
LUNG CANCER · Q1 JOURNAL - RANK #19/108
The phase III APPLE trial assessed the efficacy of adding bevacizumab to atezolizumab plus carboplatin and pemetrexed (APP) for treating metastatic nonsquamous non-small cell lung cancer (NSCLC), focusing on overall survival (OS), progression-free survival, and safety. In this prospective, randomized trial of 412 patients (287 driver oncogene-negative and 124 driver oncogene-positive), median OS was 28.0 months for the APPB arm vs. 25.7 months for APP (HR: 0.88, 95% CI: 0.70–1.10). While no overall OS benefit was observed, a favorable OS trend (HR: 0.71, 95% CI: 0.47–1.08) was noted for the driver oncogene-positive subgroup receiving bevacizumab. The study concludes that adding bevacizumab to APP may hold potential for patients with driver oncogene-positive NSCLC who have failed molecular-targeted therapy, without altering safety outcomes.
10.1016/j.lungcan.2026.109447
Anlotinib plus whole-brain radiotherapy for NSCLC brain metastases: a prospective, non-randomized, single-center cohort study.
SCI REP-UK · Q1 JOURNAL - RANK #25/135
This prospective, non-randomized, single-center cohort study compared anlotinib plus whole-brain radiotherapy (WBRT) versus WBRT alone for NSCLC brain metastases, administering anlotinib 8 mg starting 5 days before WBRT through the end of WBRT in 38 patients (19 per arm). Primary endpoints were intracranial objective response rate (iORR) and intracranial progression-free survival (iPFS); secondary endpoints included intracranial disease control rate (iDCR), quality of life, and adverse events, analyzed via Kaplan–Meier and Cox models. Anlotinib+WBRT improved iORR (57.90% vs 15.79%, P=0.017), iDCR (100% vs 73.68%, P=0.046), and median iPFS (6.7 vs 4.27 months; +2.43 months, P=0.038); post-WBRT antitumor therapy (8.67 vs 3.80 months, P=0.040) and fewer organ metastases (11.73 vs 3.17 months, P=0.035) were associated with longer iPFS. Adverse events included appetite loss, fatigue, gastrointestinal symptoms, hypertension, myelosuppression, and hepatic abnormalities; grade ≥3 hematologic and cognitive events were mostly manageable.
10.1038/s41598-026-52632-2
Segmentectomy versus lobectomy in non-small-cell lung cancer with pathologically invasive features: a post-hoc supplementary analysis of a multicenter, Phase 3 trial JCOG0802/WJOG4607L.
J THORAC ONCOL · Q1 JOURNAL - RANK #3/108TOP-TIER
This post-hoc supplementary analysis of the JCOG0802/WJOG4607L phase 3 trial investigated segmentectomy versus lobectomy in clinical stage IA NSCLC (≤2 cm) with pathologically invasive features (lymphatic, vascular, pleural invasion or lymph node metastasis). Of 1,106 randomized patients, 298 (27%) met inclusion criteria, with 164 in lobectomy and 134 in segmentectomy arms. At median 7.1 years follow-up, segmentectomy showed trend toward better OS (HR 0.657, p=0.0936) and significantly reduced deaths from other causes (HR 0.359), but increased locoregional relapse (HR 2.234). Segmentectomy may offer survival benefit despite higher locoregional relapse risk.
10.1016/j.jtho.2026.103916
The SHERPA trial: A phase I study combining SHP2 inhibitor RMC-4630 and ERK inhibitor LY3214996 in patients with KRAS-mutant pancreatic, non-small cell lung and colorectal cancer.
EUR J CANCER · Q1 JOURNAL - RANK #45/326
SHP2 inhibitor RMC-4630 plus ERK inhibitor LY3214996 were tested in a phase I 3+3 dose-escalation trial of 24 patients with KRAS-mutant pancreatic, non-small cell lung, or colorectal cancer. The primary objective was determining the recommended phase 2 dose (RP2D), with patients receiving RMC-4630 weekly and LY3214996 daily in 28-day cycles. Dose-limiting toxicities at three of four dose levels included grade 3 thrombocytopenia, grade 2 decreased left ventricular ejection fraction, and grade 3 acute kidney injury and diarrhea. Insufficient drug exposure was reached due to toxicity, no radiological responses were observed, and the trial was discontinued without establishing an RP2D.
10.1016/j.ejca.2026.116782
Simplified perioperative serplulimab and chemotherapy for resectable squamous NSCLC: a phase II trial with biomarker analysis.
J IMMUNOTHER CANCER · Q1 JOURNAL - RANK #12/183TOP-TIER
This investigator-initiated, single-arm phase II trial evaluated a four-cycle perioperative regimen of serplulimab plus taxane-carboplatin in resectable stage II–IIIA squamous NSCLC, with MPR as the primary endpoint. Patients received 2–3 neoadjuvant cycles, surgery, and 1–2 adjuvant cycles; 30 were enrolled and 29 underwent surgery. Among all enrolled patients, MPR and pCR were 76.67% and 50.00%, respectively; R0 resection was 96.55% (28/29), and ORR was 73.33% (95% CI 54.11%–87.72%); grade ≥3 treatment-related adverse events were mainly hematologic and manageable, and EFS/OS are immature. Exploratory ctDNA analysis (n=27) showed ctDNA clearance strongly correlated with pCR (p=0.004), supporting the regimen’s promising efficacy and acceptable safety and warranting phase III confirmation.
10.1136/jitc-2025-014437
May 04 – May 11, 2026
A multicenter prospective study of single nucleotide polymorphisms in the PDCD1 (programmed cell death 1) gene in patients with metastatic lung adenocarcinoma treated with pembrolizumab.
LUNG CANCER · Q1 JOURNAL - RANK #19/108
This multicenter prospective study evaluated the impact of single nucleotide polymorphisms (SNPs) in the PDCD1 gene on progression-free survival (PFS) in 141 patients with metastatic lung adenocarcinoma (MLA) treated with pembrolizumab-based therapies. Patients with PD-L1 ≥50% received pembrolizumab monotherapy, while those with PD-L1 <50% underwent pembrolizumab plus chemotherapy. The study found a significant association between the rs7421861 G-allele and poorer PFS, with G/G carriers exhibiting the worst outcomes (median PFS: 6 months versus 23 months for the A/A genotype; HR 2.85; 95% CI 1.53-5.29; p=0.001). The study concluded that rs7421861G-allele is linked to adverse outcomes and requires further validation in pembrolizumab-treated MLA patients.
10.1016/j.lungcan.2026.109383
MORPHEUS-Lung: biomarkers and clinical response to atezolizumab + bevacizumab + stereotactic body radiotherapy in patients with metastatic non-small cell lung cancer.
LUNG CANCER · Q1 JOURNAL - RANK #19/108
The MORPHEUS-Lung study (NCT03337698) investigates the efficacy and potential biomarkers associated with the combination of atezolizumab, bevacizumab, and stereotactic body radiotherapy (SBRT) in patients with metastatic non-small cell lung cancer. This exploratory analysis analyzed tumor samples from 58 patients (atezolizumab + bevacizumab + SBRT, n = 26; control [docetaxel], n = 32) using single-cell and bulk RNA sequencing. Key findings revealed associations between enhanced clinical response and increased expression of resident-memory CD8 T cells and specific macrophage genes (P values between 0.018 and 0.027), with identified gene signatures correlating to improved survival outcomes in the confirmatory cohort. These results highlight potential biomarkers for precision medicine targeting immune and macrophage activation in NSCLC treatment using atezolizumab + bevacizumab + SBRT.
10.1016/j.lungcan.2026.109354
Phase II study of ramucirumab plus erlotinib for treatment-naïve patients with EGFR-mutant non-squamous non-small cell lung cancer and pleural effusion (RELAY-Effusion).
LUNG CANCER · Q1 JOURNAL - RANK #19/108
RELAY-Effusion was a multicenter, single-arm phase II clinical trial assessing ramucirumab 10 mg/kg every 2 weeks plus daily erlotinib 150 mg in 40 previously untreated patients with EGFR-mutant non-squamous NSCLC and malignant pleural effusion. Participants received therapy until progression or intolerable toxicity; progression-free survival (primary endpoint), objective response rate, overall survival, drainage-free survival, and safety were recorded over a median 29.5-month follow-up. Median PFS reached 12.9 months (95% CI 7.3–16.7), median OS 36.3 months (95% CI 28.5–NA), 12-month OS 87.5%, ORR 77.5% (95% CI 61.5–89.2), and drainage-free survival 33.0 months; grade 3/4 treatment-related adverse events occurred in 22.5% of patients. Although the predefined PFS target was unmet, the regimen offered durable effusion control with acceptable safety, suggesting clinical utility for this high-risk subgroup.
10.1016/j.lungcan.2026.109432
Low-dose radiotherapy synergizes with PD-1 blockade to achieve durable survival in advanced NSCLC through antitumor neutrophil programming.
SIGNAL TRANSDUCT TAR · Q1 JOURNAL - RANK #1/319TOP-TIER
This study reports a phase I clinical trial evaluating TRIDENT, a novel combination of low-dose radiotherapy (LDRT) to large tumors, high-dose radiotherapy (HDRT) to small tumors, and PD-1 blockade for treatment-naïve, PD-L1-positive advanced non-small cell lung cancer (NSCLC). Among 29 patients, the TRIDENT regimen achieved a median overall survival (mOS) of 51.3 months (95% CI: 20.7-not reached), significantly better than standard chemoimmunotherapy outcomes. Mechanistically, TRIDENT elicited systemic antitumor immunity via TNF-α⁺ neutrophils, which enhanced CD8⁺ T-cell function through ICAM-1-LFA-1 interactions, supported by spatial transcriptomics analyses and biomarker correlations. These findings position TRIDENT as a promising strategy warranting further evaluation in ongoing phase II randomized trials.
10.1038/s41392-026-02712-6
Apr 27 – May 04, 2026
Early ctDNA stratifies survival in locally advanced and oligometastatic lung cancer treated with radiotherapy.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This prospective phase II trial evaluated baseline and mid-treatment ctFE in 26 patients with unresectable stage IIB-III NSCLC who received MR-guided hypofractionated chemoRT followed by immunotherapy to assess risk stratification. Blood samples were drawn at baseline and mid-treatment (day 10-14) to measure ctFE and Max VAF, with an applied threshold validated in two external cohorts (LA-RW, n=94; OM-RW, n=309). Baseline ctFE was prognostic for OS (HR 5.93, p=0.005) and PFS (HR 11.08, p<0.001), which remained significant at mid-treatment (OS: HR 7.08; PFS: HR 12.06; both p<0.001). Early ctFE dynamics defined three molecular response groups with markedly different median OS (60.8 vs. 13.0 vs. 2.9 months, p<0.001), supporting its practical utility as a biomarker for precision treatment adaptation.
10.1158/1078-0432.CCR-25-4983
Tiragolumab Plus Atezolizumab and Chemotherapy for Advanced Nonsquamous Non-Small Cell Lung Cancer: The Phase 3 SKYSCRAPER-06 Randomized Clinical Trial.
JAMA ONCOL · Q1 JOURNAL - RANK #14/326TOP-TIER
The primary objective was to evaluate the efficacy and safety of tiragolumab plus atezolizumab plus chemotherapy versus placebo plus pembrolizumab plus chemotherapy in advanced nonsquamous NSCLC. This phase 3 randomized clinical trial recruited 542 patients with previously untreated, locally advanced unresectable or metastatic NSCLC, who were assigned 1:1 to each treatment arm. While the tiragolumab plus atezolizumab plus chemotherapy group showed a median PFS of 8.3 months versus 9.9 months and median OS of 18.9 months versus 23.1 months, both differences were not statistically significant. Consequently, the study was terminated early and the primary endpoints were not met.
10.1001/jamaoncol.2026.0818
Long-Term Impact of First-Line Amivantamab Plus Lazertinib Versus Osimertinib on Mechanisms of Acquired Resistance in MARIPOSA: A Brief Report.
J THORAC ONCOL · Q1 JOURNAL - RANK #3/108TOP-TIER
This study evaluated the long-term effects of first-line amivantamab-lazertinib versus osimertinib on acquired resistance mechanisms in EGFR-mutated advanced non-small cell lung cancer (NSCLC). MARIPOSA (NCT04487080), a prospective clinical trial, found that amivantamab-lazertinib improved overall survival (HR 0.75, P=0.005) and extended second-line progression-free survival (8.4 vs 5.3 months; HR 0.72, P=0.02) compared to osimertinib. The study also used Guardant360® next-generation sequencing on baseline and end-of-treatment samples to identify resistance mechanisms, with significant reductions in MET amplifications (3.4% vs 13.1%, P=0.002) and secondary EGFR mutations (1.4% vs 7.6%, P=0.01) in the amivantamab-lazertinib group. Results suggest a biological change in resistance pathways, supporting the regimen’s efficacy in managing EGFR-mutated NSCLC.
10.1016/j.jtho.2026.103894
Clinical efficacy of comprehensive traditional Chinese medicine in adjuvant therapy for stage Ib-IIIa resected non-small cell lung cancer: a multi-center, randomized, double-blind, placebo-controlled trial.
FRONT PHARMACOL · Q1 JOURNAL - RANK #51/352
This prospective, multi-center, randomized, double-blind, placebo-controlled trial evaluated the efficacy of Traditional Chinese Medicine (TCM) as an adjuvant to platinum-based chemotherapy in stage IB-IIIA non-small cell lung cancer (NSCLC). A total of 286 patients were randomly assigned to receive four cycles of chemotherapy plus TCM granules or placebo, followed by four cycles of Huachansu or placebo injections. Although the 2-year disease-free survival (DFS) rates showed a non-significant trend (65.70% vs. 55.40%, p=0.08), the TCM group achieved a significantly longer DFS (37.8 months vs. 31.6 months, HR=0.73, p=0.045). TCM was well tolerated and improved quality of life, underscoring its value in adjuvant therapy for resected NSCLC.
10.3389/fphar.2026.1776888
Apr 20 – Apr 27, 2026
A Phase 1 dose-escalation study to evaluate safety, pharmacokinetics, and pharmacodynamics of OSE-279, an anti-PD-1 monoclonal antibody in patients with advanced solid tumours.
EUR J CANCER · Q1 JOURNAL - RANK #45/326
This phase 1, open-label, dose-escalation trial evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of OSE-279, an anti-PD-1 monoclonal antibody, in 20 patients with advanced solid tumors. Patients received intravenous OSE-279 at 100 mg q3w, 300 mg q3w, or 600 mg q6w. Key findings included two recommended phase 2 doses (300 mg q3w, 600 mg q6w), linear PK with >80% receptor occupancy, and durable responses: 1 complete response, 4 partial responses, and 7 stable disease, with response duration ranging from 6.8 to 18.4 months. The authors concluded OSE-279 monotherapy is well tolerated and shows durable antitumor activity, with the trial continuing in combination with a therapeutic cancer vaccine.
10.1016/j.ejca.2026.116729
Deulorlatinib (TGRX-326) in ALK gene fusion positive non-small cell lung cancer after failure of second-generation inhibitors (DRAGON): a single-arm, multicenter, phase 2 trial.
J THORAC ONCOL · Q1 JOURNAL - RANK #3/108TOP-TIER
This single-arm, multicenter, phase 2 trial aimed to evaluate the efficacy and safety of deulorlatinib in ALK-positive NSCLC patients who had failed second-generation ALK inhibitors. Eligible patients received 60 mg once daily, with the primary endpoint of objective response rate and secondary endpoints including disease control rate, progression-free survival, duration of response, overall survival, intracranial efficacy, and safety. Among 158 evaluable patients, the ORR was 43.7% (95% CI, 35.8-51.8), median PFS was 11.1 months (95% CI, 8.3-13.7), and in those with measurable CNS metastases (N=43), intracranial ORR was 55.8% (95% CI, 39.9-70.9). Given its favorable safety profile (96.3% overall TRAEs, 47.2% grade ≥3), deulorlatinib demonstrates encouraging efficacy—including those with G1202R mutation—and represents a promising new option for this population.
10.1016/j.jtho.2026.103737
Fianlimab, a human lymphocyte activation gene-3 monoclonal antibody, in combination with cemiplimab: Tumor-specific expansion cohorts in advanced malignancies.
CANCER-AM CANCER SOC · Q1 JOURNAL - RANK #68/326
This phase 1 dose-expansion study evaluated fianlimab (anti-LAG-3) plus cemiplimab (anti-PD-1) in patients with advanced NSCLC, ccRCC, HNSCC, and CSCC. Patients received 1600 mg fianlimab plus 350 mg cemiplimab every 3 weeks for up to 24 months, with ORR per RECIST 1.1 as the primary endpoint. Investigator-assessed ORR was 27% in NSCLC-N, 7% in NSCLC-E, 20% in ccRCC-N, 7% in ccRCC-E, 33% in HNSCC-N, 7% in HNSCC-E, and 20% in CSCC-E. The combination demonstrated modest efficacy with acceptable safety, warranting further investigation.
10.1002/cncr.70396
Patient-reported outcomes from the LAURA study: osimertinib in patients with unresectable stage III EGFR-mutated non-small cell lung cancer after definitive chemoradiotherapy.
EUR J CANCER · Q1 JOURNAL - RANK #45/326
The LAURA study was a prospective clinical trial investigating osimertinib versus placebo in patients with unresectable stage III EGFR-mutated NSCLC after definitive chemoradiotherapy. Patients were evaluated for patient-reported outcomes using EORTC QLQ-C30/LC13 and PRO-CTCAE, with mixed model repeated measures and time-to-deterioration analyses performed. Minimal changes from baseline were observed over 40 weeks for key scales, and hazard ratios for confirmed deterioration in symptoms or functioning ranged from 1.00 (appetite loss) to 1.46 (pain in chest). With a significant progression-free survival benefit and manageable safety profile, osimertinib was shown to be well-tolerated and beneficial in this population.
10.1016/j.ejca.2026.116744
Elisrasib Elicits Clinical Benefit in KRASG12C-mutant NSCLC.
CANCER DISCOV · Q1 JOURNAL - RANK #10/326TOP-TIER
This phase I/II prospective clinical trial evaluated elisrasib, a next-generation KRASG12C inhibitor, in patients with locally advanced or metastatic KRAS G12C-mutant non-small cell lung cancer. Eligible patients included both those naïve to KRASG12C inhibitors and those refractory to prior such treatments, all actively assigned to the drug intervention. Robust and durable clinical responses were observed, with disease control rates of 98.5% in inhibitor-naïve patients and 83.9% in refractory patients. The study concludes that elisrasib provides considerable clinical benefit in this population.
10.1158/2159-8290.CD-NW2026-0041
Zoldonrasib Deemed Safe, Effective in KRAS G12D-mutant NSCLC.
CANCER DISCOV · Q1 JOURNAL - RANK #10/326TOP-TIER
In a phase I clinical trial investigating zoldonrasib, a selective KRAS G12D inhibitor for non-small cell lung cancer, participants received active treatment targeting KRAS mutations. A total of 52% achieved an objective response, 93% achieved disease control, the median progression-free survival was 11.1 months, and the 12-month overall survival was 73%. This prospective design utilized standard oncology endpoints to assess both safety and efficacy in a defined patient population. Zoldonrasib showed promising clinical activity and a manageable safety profile, supporting further evaluation in larger trials.
10.1158/2159-8290.CD-NW2026-0040
Neoadjuvant Atezolizumab and Chemotherapy for Non-Squamous Non-Small Cell Lung Cancer: Efficacy and Safety Results of an Open-Label, Single-Arm, Phase II Trial.
INT J CANCER · Q1 JOURNAL - RANK #77/326
This open-label, single-arm, phase II trial evaluated the efficacy and safety of neoadjuvant atezolizumab plus carboplatin/nab-paclitaxel in 20 patients with resectable non-squamous non-small cell lung cancer. The primary endpoint was major pathologic response (MPR), achieved in 45% of patients (9/20), including 25% (5/20) with complete pathological response; 65% (13/20) experienced grade ≥3 adverse events. All patients underwent R0 resection, and tumor viability correlated with CT and SUV changes (p=0.018, p=0.006). The study concludes that atezolizumab-based chemoimmunotherapy is promising for preoperative treatment, warranting further investigation and biomarker development.
10.1002/ijc.70508
Apr 13 – Apr 20, 2026
Efficacy, safety, and biomarker analysis of datopotamab deruxtecan in advanced non-small cell lung cancer: ICARUS-LUNG01 phase 2 study.
CANCER CELL · Q1 JOURNAL - RANK #5/326TOP-TIER
This multicenter, prospective phase II clinical trial (ICARUS-LUNG01) evaluated the efficacy, safety, and biomarker correlates of the TROP2-directed antibody–drug conjugate datopotamab deruxtecan in 100 previously treated patients with advanced non-small cell lung cancer. All participants received single-arm treatment with Dato-DXd and were followed for clinical outcomes and serial tumor biomarker assessments. The study demonstrated an objective response rate of 26.0 % and a median progression-free survival of 3.6 months, with higher activity in non-squamous tumors; translational analyses linked lack of TROP2 cytoplasmic staining and early DNA-repair pathway activation to resistance, while immune pathway activation correlated with response. Investigators concluded that Dato-DXd shows clinically meaningful activity and that further phase III trials are required to validate predictive biomarkers for patient selection.
10.1016/j.ccell.2026.03.017
Safety and Antitumor Activity of Farletuzumab Ecteribulin in Patients With NSCLC: Phase I Expansion Results.
JTO CLIN RES REP · Q1 JOURNAL - RANK #26/108
The study evaluated the safety and antitumor activity of farletuzumab ecteribulin (FZEC) in patients with advanced NSCLC adenocarcinoma in a phase I expansion trial. Fifteen patients received FZEC 0.9 mg/kg intravenously every 3 weeks, with safety and efficacy outcomes including objective response rate (ORR), progression-free survival, and overall survival assessed. Key findings included an ORR of 6.7% (1 partial response), a disease control rate of 53.3%, and median progression-free survival of 2.7 months, with manageable adverse events. The study concluded that FZEC showed modest antitumor activity in heavily pretreated NSCLC patients, particularly those with FRα expression.
10.1016/j.jtocrr.2026.100962
Disease characteristics and treatment outcomes in patients with resected early-stage ALK-positive non-small cell lung cancer from the randomized ALINA trial.
LUNG CANCER · Q1 JOURNAL - RANK #19/108
This exploratory analysis from the phase III ALINA trial examined whether the disease-free survival benefit of adjuvant alectinib versus chemotherapy in patients with resected, ALK-positive non-small cell lung cancer was consistent across surgical characteristic subgroups and when reclassifying patients using the 8th edition AJCC/UICC staging system. The global, open-label, randomized trial enrolled patients ≥18 years with stage IB (≥4 cm), II, or IIIA disease who were assigned to receive either alectinib 600 mg twice daily for 24 months or four cycles of platinum-based chemotherapy. Patients receiving alectinib demonstrated longer DFS compared to chemotherapy regardless of disease stage (AJCC/UICC 8th edition), nodal status, tumor size, or other surgical characteristics, with most patients having tumors ≤3 cm (57.4%), stage IIIA disease (52.1%), and N2 nodal status (50.6%). The analysis concluded that alectinib is the first ALK inhibitor to show consistent DFS benefit over chemotherapy in this patient population across all evaluated disease characteristics.
10.1016/j.lungcan.2026.109385
Longitudinal Analysis of Peripheral Blood CD4+ T-Cell Profiles and Clinical Outcomes in Metastatic Non-Small-Cell Lung Cancer Patients Following Bronchoscopic Cryotherapy and Pembrolizumab-Based Therapy.
INT J MOL SCI · Q1 JOURNAL - RANK #72/319
The primary objective was to assess peripheral blood T-cell changes and clinical outcomes in metastatic NSCLC patients randomized to bronchoscopic cryotherapy plus pembrolizumab-based therapy or standard therapy alone. This prospective, randomized, controlled trial analyzed 34 cryotherapy and 42 control patients using flow cytometry of blood samples at three time points and radiologic response per RECIST 1.1, with survival outcomes calculated via Kaplan-Meier and Cox regression. Key findings included a significant increase in CD8+ T cells (p=0.013), reduced Tregs at week 3 (p=0.024), and a higher overall response rate in the cryotherapy group (41.2% vs. 16.7%; p=0.022), though median PFS and OS were numerically longer but not statistically significant. The principal conclusion is that bronchoscopic cryotherapy prior to pembrolizumab-based therapy modifies peripheral immune profiles and improves objective response rates without significant benefit in PFS or OS.
10.3390/ijms27072927
Apr 06 – Apr 13, 2026
First-Line Sacituzumab Govitecan Plus Pembrolizumab and Carboplatin in Metastatic Non-Small Cell Lung Cancer: Nonsquamous and Squamous Cohorts of the EVOKE-02 Study.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
EVOKE-02 (NCT05186974) is a multicohort, prospective phase II clinical trial evaluating first-line sacituzumab govitecan (SG) plus pembrolizumab and carboplatin in adults with metastatic non-small cell lung cancer (mNSCLC) without actionable genomic alterations, using 21-day cycles (SG 10 mg/kg IV on days 1 and 8, later reduced to 7.5 mg/kg after a planned safety review; pembrolizumab 200 mg IV day 1; carboplatin AUC5 day 1). Among nonsquamous (n=54) and squamous (n=41) cohorts, objective response rate (ORR) was 45.1% (95% CI 3.1–59.7) and 39.0% (95% CI 24.2–55.5), respectively; median progression-free survival (PFS) was 8.1 months (95% CI 5.2–15.0) and 8.3 months (95% CI 4.3–11.2), respectively, with ORR 66.7% (95% CI 34.9–90.1) in PD-L1 tumor proportion score ≥50%. Safety showed grade ≥3 treatment-emergent adverse events in 57 patients (86.4%) and treatment discontinuation due to adverse events in 12 patients (18.2%), prompting SG dose reduction to 7.5 mg/kg for myelosuppression. The study concludes that SG plus pembrolizumab and carboplatin demonstrates antitumor activity and is tolerable at the adjusted SG dose in first-line mNSCLC.
10.1158/1078-0432.CCR-25-4485
A first-in-human phase 1 clinical trial evaluating clinical activity and proof-of-mechanism of tobemstomig, a PD1-LAG3 bispecific antibody, in patients with CPI-experienced melanoma.
CLIN CANCER RES · Q1 JOURNAL - RANK #29/326TOP-TIER
This study is a first-in-human, open-label, phase 1 clinical trial evaluating the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of the PD1-LAG3 bispecific antibody, tobemstomig, in patients with advanced and/or metastatic solid tumors. The study included 35 patients in the dose-escalation phase and 69 patients in the expansion phase, across various tumor types. Partial responses were observed in 15% (6/41) of CPI-experienced melanoma patients and proof-of-mechanism was demonstrated by increased CD8+ T cell activity, among other immunological effects. Tobemstomig demonstrated a tolerable safety profile with a recommended dose established at 2100 mg Q2W, supporting further investigation in earlier disease settings.
10.1158/1078-0432.CCR-25-4478