Bispecific antibodies (55 trials) — rilvegostomig (PD-1/TIGIT), ivonescimab (PD-1/VEGF, BLA accepted by FDA), cadonilimab (PD-1/CTLA-4)
Standard of care: Treatment depends entirely on your driver mutation. EGFR-mutated: Osimertinib first-line (adjuvant for Stage IB-IIIA). ALK-rearranged: Lorlatinib first-line. KRAS G12C: Sotorasib or adagrasib after prior therapy (first-line combos in Phase 3). No driver mutation: Pembrolizumab + chemotherapy (PD-L1 ≥50%: pembrolizumab alone). Stage III unresectable: Chemoradiation → durvalumab consolidation. Other approved targets: RET (selpercatinib), BRAF V600E (dabrafenib+trametinib), NTRK (larotrectinib/entrectinib), HER2-mutant (T-DXd), MET exon 14 (capmatinib/tepotinib).
Key Biomarkers for Trial Eligibility
NSCLC has the most biomarker-driven treatment landscape of any cancer. Knowing your mutation determines everything:
EGFR mutations (~15-20% of adenocarcinoma) — exon 19 deletion, L858R (classical, osimertinib), exon 20 insertion (~2%, needs specific inhibitors like sunvozertinib/zipalertinib), T790M (resistance mutation). 187 recruiting trials.
KRAS G12C (~13% of adenocarcinoma) — once undruggable, now has 2 FDA-approved inhibitors and 66 recruiting trials including first-line combinations and pan-RAS agents.
ALK rearrangement (~5%) — lorlatinib is standard first-line. 37 recruiting trials focus on resistance and adjuvant use.
Comprehensive genomic profiling (e.g., Foundation Medicine, Tempus, Guardant360) is essential — it tests all actionable mutations in one test. Without it, you may miss targeted therapy options.
Know your mutation and PD-L1 status? Get matched to NSCLC trials in minutes.
Lorlatinib is standard first-line. The 4th-generation ALK inhibitor neladalkib (NVL-655) is now in Phase 3 in the TKI-naive setting — designed to overcome the G1202R compound-mutation resistance that limits lorlatinib:
NCT06765109 - Neladalkib (NVL-655) for TKI-naive patients with advanced ALK-positive NSCLC (Phase 3, 4th-gen ALK inhibitor entering 1L)
ROS1-Rearranged (20 trials)
NCT06564324 - Taletrectinib vs SOC in ROS1+ advanced NSCLC (Phase 3)
NCT07154706 - TRUST-IV: Taletrectinib adjuvant in ROS1+ NSCLC (Phase 3)
For patients without actionable driver mutations, checkpoint immunotherapy ± chemotherapy is standard. Novel approaches:
First-line:
NCT06627647 - Rilvegostomig or Pembrolizumab + Chemo for first-line metastatic NSCLC (Phase 3, global head-to-head of the PD-1/TIGIT bispecific vs anti-PD-1 backbone)
NCT06868277 - Rilvegostomig or Pembrolizumab monotherapy, PD-L1-high (Phase 3)
NCT06692738 - Rilvegostomig or Pembrolizumab + Chemo for squamous NSCLC (Phase 3)
NCT05215340 - Dato-DXd + Pembrolizumab vs Pembrolizumab first-line (Phase 3)
NCT06170788 - Sacituzumab Tirumotecan + Pembrolizumab vs Pembrolizumab (Phase 3)
Personalized mRNA cancer vaccine (KEYNOTE-V940 program):
NCT06077760 - Intismeran Autogene (V940, Moderna personalized mRNA cancer vaccine) + Pembrolizumab vs Placebo + Pembrolizumab in resected NSCLC (Phase 3, the lung-cancer half of the KEYNOTE-V940 program; the first personalized-neoantigen mRNA vaccine to reach Phase 3 in NSCLC)
Pretreated / second-line:
NCT07291037 - Datopotamab Deruxtecan vs Docetaxel, TROP2+ (Phase 3)
NCT07144280 - PF-08046054/SGN-PDL1V (ADC) vs Docetaxel (Phase 3)
NCT06616584 - Cemiplimab added to chemo after prior IO (Phase 3)
Stage III unresectable (consolidation):
NCT05211895 - Durvalumab + Domvanalimab after chemoradiation (Phase 3)
NCT07361497 - Pumitamig vs Durvalumab after chemoradiation (Phase 3)
How do I find NSCLC clinical trials for my mutation?
Enter your lung cancer details into ClinTrialFinder — including your specific mutation (EGFR exon type, KRAS G12C, ALK, ROS1, etc.), PD-L1 expression level, stage, and prior treatments. The AI matches you with trials based on your specific profile in minutes. No login required.
What NSCLC trials are currently recruiting?
There are 1,002 recruiting interventional trials for NSCLC in May 2026 including EGFR inhibitors (~187, with firmonertinib NCT07185997 entering Phase 3), checkpoint immunotherapy combinations (~314, with new entrants rilvegostomig PD-1/TIGIT NCT06627647 and intismeran V940 personalized mRNA cancer vaccine NCT06077760), ADCs (~85, including Dato-DXd + osimertinib NCT06417814), KRAS G12C inhibitors (~66, with adagrasib + pembro + chemo 1L NCT06875310), bispecific antibodies (~55), 4th-generation ALK inhibitor neladalkib NVL-655 Phase 3 (NCT06765109), and targeted therapies for ALK, ROS1, RET, MET, HER2, BRAF, and NTRK.
Should I get comprehensive genomic profiling for lung cancer?
Yes — comprehensive genomic profiling is essential for NSCLC. Over 60% of lung adenocarcinoma patients have a potentially actionable driver mutation (EGFR, KRAS, ALK, ROS1, MET, RET, HER2, BRAF, NTRK). Each has FDA-approved therapies or active trials. A single test (Foundation Medicine, Tempus, Guardant360) covers all targets. Without profiling, you may miss targeted therapy options that are far more effective than chemotherapy alone.
What are PD-1/VEGF bispecific antibodies and why are they important for NSCLC?
PD-1/VEGF bispecifics are a new class of drugs that block both the PD-1 immune checkpoint and VEGF (blood vessel growth) in a single molecule. At AACR 2026, four competitors showed 47-62% response rates in first-line NSCLC — potentially replacing pembrolizumab. Ivonescimab already has an FDA application accepted. These are in multiple Phase 3 trials recruiting now.
Find Lung Cancer Trials Matched to Your Situation
Enter your mutation type, PD-L1 status, and treatment history to get AI-matched trial results in minutes.
This page is for information only and is not medical advice. ClinTrialFinder helps you find clinical trials that may match your situation, but enrollment decisions and treatment choices should always be made with your oncologist or healthcare team. Trial eligibility, recruitment status, and treatment details can change — verify directly with the trial sponsor or on ClinicalTrials.gov before acting on any information here.
