Non-Small Cell Lung Cancer (NSCLC) Clinical Trials (April 2026): 1,046 Recruiting Interventional Studies

Last updated: April 28, 2026

Current Clinical Trial Landscape

Active research areas in 2026:

Checkpoint immunotherapy combinations (314 trials) — pembrolizumab, durvalumab, cemiplimab + novel agents, PD-1/VEGF bispecifics racing to replace Keytruda
EGFR-targeted therapies (187 trials) — next-gen TKIs (furmonertinib, sunvozertinib, zipalertinib), EGFR exon 20 insertion inhibitors, ADCs for post-osimertinib
Antibody-drug conjugates (85 trials) — datopotamab deruxtecan, sacituzumab tirumotecan, T-DXd, PD-L1-targeted ADCs. Transforming both first-line and post-IO treatment
KRAS G12C inhibitors (66 trials) — sotorasib, adagrasib, olomorasib, D-1553, daraxonrasib (pan-RAS). Moving to first-line combinations
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.
PD-L1 expression (TPS) — determines immunotherapy eligibility. TPS ≥50%: pembrolizumab monotherapy. TPS 1-49%: pembrolizumab + chemo. TPS <1%: chemo + IO or chemo alone.
ROS1 rearrangement (~1-2%) — crizotinib, entrectinib approved. Taletrectinib in Phase 3.
MET exon 14 skipping / amplification (~3-4%) — capmatinib, tepotinib approved. MET amplification also emerges as EGFR resistance mechanism.
RET fusion (~1-2%) — selpercatinib approved. Next-gen SY-5007 in Phase 3.
HER2 mutations (~2-3%) — T-DXd approved. New ADCs in Phase 3 trials.
BRAF V600E (~2%) — dabrafenib + trametinib approved.
NTRK fusion (<1%) — larotrectinib, entrectinib approved.

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.

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Recruiting Trials by Biomarker

EGFR-Mutated (187 trials)

Osimertinib is standard first-line. Key frontiers: combination strategies, adjuvant expansion, and post-osimertinib options:

First-line combinations:
- NCT06970639 - Furmonertinib + Chemo vs Osimertinib (Phase 3)
- NCT06674343 - Furmonertinib 160mg first-line for EGFR classical mutations (Phase 3)
- NCT07183189 - SHR-A2009 + Aumolertinib vs Aumolertinib first-line (Phase 3)
- NCT06734391 - JMT101 + Osimertinib vs Osimertinib first-line (Phase 3)
After osimertinib progression (MET amplification):
- Osimertinib + MET inhibitor combinations (savolitinib, tepotinib, capmatinib) — multiple Phase 3 trials recruiting
After osimertinib (ADC-based):
- NCT06350097 - Osimertinib ± Datopotamab Deruxtecan first-line (Phase 3)
- NCT06416814 - Dato-DXd ± Osimertinib vs Chemo after EGFR TKI (Phase 3)
- NCT06305754 - Sacituzumab Tirumotecan vs Pemetrexed/Carboplatin after EGFR TKI (Phase 3)
- NCT06927986 - SYS6010 (ADC) vs Chemo for EGFR-mutated NSCLC (Phase 3)
EGFR exon 20 insertion:
- NCT06452277 - Sevabertinib vs SOC (Phase 3)
- NCT07128199 - Zipalertinib adjuvant (Phase 3)
- NCT07182682 - Sunvozertinib adjuvant in early-stage NSCLC with EGFR ex20ins (Phase 3)
Adjuvant:
- NCT04853342 - Furmonertinib adjuvant vs Placebo (Phase 3)
- NCT06041776 - Befotertinib adjuvant in stage IB-IIIB (Phase 3)

KRAS G12C-Mutated (66 trials)

Sotorasib and adagrasib are approved. Next-gen inhibitors and combinations are the frontier:

First-line combinations:
- NCT05920356 - Sotorasib + Chemo vs Pembrolizumab + Chemo first-line (Phase 3)
- NCT06119581 - Olomorasib + Pembrolizumab ± Chemo first-line (Phase 3)
- NCT06416410 - JAB-21822 + JAB-3312 (SHP2i) vs SOC first-line (Phase 3)
- NCT07174908 - IN10018 (FAKi) + D-1553 vs SOC first-line non-squamous (Phase 3)
Pretreated:
- NCT04613596 - Adagrasib ± Pembrolizumab (Phase 2/3)
- NCT06300177 - D-1553 vs Docetaxel (Phase 3)
RAS multi-selective (pan-KRAS):
- NCT06881784 - Daraxonrasib (RMC-6236) in RAS-mutated NSCLC (Phase 3, RASolve 301)
Adjuvant:
- NCT07431827 - Pembrolizumab ± Calderasib (MK-1084) adjuvant in resected KRAS G12C (Phase 3)
- NCT06890598 - Olomorasib + SOC in resected/unresectable KRAS G12C (Phase 3)

ALK-Rearranged (37 trials)

Lorlatinib is standard first-line. Research focuses on resistance mechanisms and adjuvant use.

ROS1-Rearranged (20 trials)

NCT06564324 - Taletrectinib vs SOC in ROS1+ advanced NSCLC (Phase 3)
NCT07154706 - TRUST-IV: Taletrectinib adjuvant in ROS1+ NSCLC (Phase 3)

Other Targetable Mutations

HER2-mutant (43 trials):
- NCT07178795 - BL-M07D1 (ADC) vs Pembrolizumab + Chemo first-line HER2-mutant (Phase 3)
- NCT06899126 - T-DXd + Pembrolizumab + Chemo first-line HER2-overexpressing (Phase 3)
MET (31 trials): Savolitinib, tepotinib, capmatinib for MET exon 14 skipping and MET amplification
RET (8 trials): Selpercatinib approved; NCT06031558 - SY-5007 (next-gen RET inhibitor) in RET fusion+ NSCLC (Phase 3)
BRAF V600E (6 trials): NCT05768178 - DETERMINE: Vemurafenib + Cobimetinib in BRAF+ cancers (Phase 3)

No Targetable Mutation (Immunotherapy-Based)

For patients without actionable driver mutations, checkpoint immunotherapy ± chemotherapy is standard. Novel approaches:

First-line:
- NCT06868277 - Rilvegostomig (PD-1/TIGIT bispecific) or Pembrolizumab monotherapy, PD-L1-high (Phase 3)
- NCT06692738 - Rilvegostomig or Pembrolizumab + Chemo for squamous NSCLC (Phase 3)
- NCT06357533 - Dato-DXd + Rilvegostomig first-line non-squamous (Phase 3)
- NCT05215340 - Dato-DXd + Pembrolizumab vs Pembrolizumab first-line (Phase 3)
- NCT06170788 - Sacituzumab Tirumotecan + Pembrolizumab vs Pembrolizumab (Phase 3)
Pretreated / second-line:
- NCT06074588 - Sacituzumab Tirumotecan vs Chemo, non-squamous (Phase 3)
- 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)
- NCT06216301 - LUNAR-2: TTFields + Pembrolizumab + Chemo for metastatic NSCLC (Phase 3)
Adjuvant / perioperative:
- NCT05487391 - QL1706 (PD-1/CTLA-4 bispecific) + Chemo adjuvant stage II-IIIB (Phase 3)
- NCT07222566 - PF-08634404 + Chemo for locally advanced squamous (Phase 3)

Novel Approaches

ADCs (85 trials): Datopotamab deruxtecan, sacituzumab tirumotecan, sigvotatug vedotin (PD-L1-targeted ADC), SYS6010 — transforming both first-line and later-line treatment
Bispecific antibodies (55 trials): Rilvegostomig (PD-1/TIGIT), ivonescimab (PD-1/VEGF), cadonilimab (PD-1/CTLA-4) — next-gen checkpoint blockade
Pan-RAS inhibitors: Daraxonrasib (RMC-6236) — first RAS multi-selective agent, targeting KRAS G12C/G12D/G12V/G13D and other RAS mutations
Tumor treating fields: TTFields + immunotherapy (LUNAR-2) — non-systemic approach for metastatic NSCLC

Showing selected notable trials. View all 1,046 recruiting interventional trials on ClinicalTrials.gov.

Frequently Asked Questions

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 1,046 recruiting interventional trials for NSCLC including EGFR inhibitors (187 trials), checkpoint immunotherapy combinations (314), ADCs (85), KRAS G12C inhibitors (66), bispecific antibodies like PD-1/VEGF and PD-1/TIGIT (55), 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

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