LUNG CANCER · White paper
Lung Cancer Clinical Trials
Approved therapies, the pivotal-trial endpoints they were judged on, the magnitude of benefit — and the drugs that failed their endpoints, and why.
Indication overview
About lung cancer — and why its trials are hard
Lung cancer is a leading cause of cancer death, accounting for roughly 13% of new U.S. cancer cases but nearly 25% of cancer deaths, with an estimated 228,820 new U.S. cases in 2023. It divides into non-small cell lung cancer (NSCLC, ~80-85%) and small cell lung cancer (SCLC, ~15-20%). NSCLC treatment has been transformed by biomarker-driven targeted therapy for EGFR, ALK, and KRAS alterations and by immune checkpoint inhibitors of PD-1/PD-L1. Osimertinib set the standard in EGFR-mutant disease (FLAURA), while pembrolizumab reshaped first-line care as monotherapy in high PD-L1 tumors (KEYNOTE-024) and with chemotherapy (KEYNOTE-189/407). Nivolumab, atezolizumab, and durvalumab added further checkpoint options, and sotorasib introduced KRAS G12C targeting. Pivotal endpoints center on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR), assessed by RECIST v1.1 with blinded independent review. Failures over the past decade span rociletinib, tivantinib, necitumumab, dacomitinib, and first-line single-agent ipilimumab, reflecting tumor genetic heterogeneity, toxicity, and endpoint challenges.
Approved therapies & pivotal evidence
What's been approved — and by how much it moved the endpoint
| Drug (brand) | Approved | Setting | Pivotal trial | Primary endpoint | Magnitude of benefit |
|---|---|---|---|---|---|
| Osimertinib (Tagrisso) | 2015 | First-line EGFR-mutant metastatic NSCLC (also adjuvant and T790M) | FLAURA (NCT02296125) | Progression-free survival (PFS) | Median PFS 18.9 vs 10.2 months (HR 0.46); median OS 38.6 vs 31.8 months |
| Pembrolizumab (Keytruda) | 2014 (NSCLC indications from 2015-2016) | First-line metastatic NSCLC, TPS >=50% monotherapy | KEYNOTE-024 (NCT02142738) | Progression-free survival (PFS) | Median PFS 10.3 vs 6.0 months (HR 0.50); OS 30.0 vs 14.2 months (HR 0.60) |
| Pembrolizumab + chemotherapy (Keytruda) | 2017 (nonsquamous), 2018 (squamous) | First-line metastatic nonsquamous NSCLC with pemetrexed/platinum | KEYNOTE-189 (NCT02578680) | Overall survival (OS) and PFS | OS HR 0.49; PFS 8.8 vs 4.9 months (HR 0.52); ORR 48% vs 19% |
| Nivolumab (Opdivo) | 2015 (NSCLC) | Previously treated metastatic squamous NSCLC | CheckMate-017 (NCT01642004) | Overall survival (OS) | Median OS 9.2 vs 6.0 months vs docetaxel (HR 0.59) |
| Durvalumab (Imfinzi) | 2018 | Consolidation after chemoradiation in unresectable Stage III NSCLC | PACIFIC (NCT02125461) | PFS and overall survival (OS) | PFS 16.8 vs 5.6 months (HR 0.52); OS HR 0.68 |
| Sotorasib (Lumakras) | 2021 | Previously treated KRAS G12C-mutated locally advanced/metastatic NSCLC | CodeBreaK 100 | Objective response rate (ORR) | ORR ~36% with durable responses (accelerated approval); first KRAS G12C inhibitor |
Where trials have failed
Drugs that missed their endpoint — and what contributed
The most instructive lessons in lung cancer development come from programmes that failed the endpoint that mattered.
| Drug / trial | Endpoint outcome | What contributed |
|---|---|---|
| Rociletinib (CO-1686) — NCT02147990 (TIGER program) | Development discontinued for NSCLC | Severe side effects, particularly hyperglycemia, and unfavorable benefit-risk vs osimertinib |
| Ipilimumab (first-line NSCLC) — NCT01471197 | Failed to meet primary PFS endpoint; NSCLC development terminated | CTLA-4 blockade added to chemotherapy did not improve outcomes in NSCLC |
| Necitumumab — NCT00982111 | Trial completed but did not achieve efficacy endpoints in the intended setting | Increased mortality from thromboembolic events limited benefit-risk |
Choosing the right endpoint
Primary endpoints that matter in lung cancer trials
- Overall Survival (OS) — Most definitive endpoint; challenged by long follow-up, confounding, and crossover to subsequent therapies
- Progression-Free Survival (PFS) — Common primary endpoint; requires standardized imaging and blinded central review to limit subjectivity and pseudo-progression
- Objective Response Rate (ORR) — Proportion with predefined tumor shrinkage by RECIST v1.1; supports accelerated approvals
- Disease-Free / Recurrence-Free Survival (DFS) — Key endpoint in adjuvant NSCLC trials (e.g., osimertinib ADAURA, atezolizumab)
- Duration of Response (DoR) — Length of sustained response; contextualizes ORR for durability
How iNGENū runs lung cancer trials
Physician-led design, built for FDA submission
Endpoint & biomarker strategy
Board-certified specialists design endpoints and patient selection aligned to current FDA guidance for this indication.
FDA-ready data
Built to ICH-GCP and 21 CFR 312.120, with direct FDA submission — data accepted by the FDA, EMA and MHRA.
Faster, lower-cost delivery
~4-week ethics via the TGA CTN scheme, up to 43.5% R&D rebate, and 80–90% below US CRO cost.
The full white paper: approved-product analyses, pivotal endpoints and trial-design strategy. Open-access · no sign-in.
Frequently asked questions
Lung Cancer clinical trials — FAQs
How has biomarker testing changed NSCLC trials?
Which endpoints support lung cancer approvals?
Why do immunotherapy and targeted combinations fail?
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