STOMACH (GASTRIC) CANCER · White paper
Stomach (Gastric) 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 stomach (gastric) cancer — and why its trials are hard
Stomach (gastric) cancer, predominantly adenocarcinoma, is the fifth most common cancer worldwide and the third leading cause of cancer death, with roughly 1 million new cases annually and the highest burden in East Asia. Because early disease is often silent, most patients present at advanced stages, making systemic therapy central. Helicobacter pylori infection, CDH1 germline mutations, HER2 overexpression, dietary factors and smoking drive risk. Treatment has shifted from cytotoxic chemotherapy toward biomarker-directed care: HER2-targeted trastuzumab (ToGA), VEGFR2 blockade with ramucirumab (REGARD/RAINBOW), PD-1 immunotherapy with nivolumab (CheckMate-649) and pembrolizumab, the HER2 antibody-drug conjugate trastuzumab deruxtecan (DESTINY-Gastric01), and in 2024 the CLDN18.2-targeting antibody zolbetuximab (SPOTLIGHT/GLOW). Pivotal trials rely on overall survival, with progression-free survival and objective response rate as supportive endpoints assessed by RECIST v1.1. Recurrent challenges include tumor-biology heterogeneity (variable HER2 and CLDN18.2 expression), geographic and ethnic differences in biology and outcomes, inadequate biomarker stratification, and rapid early progression driving dropout.
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 |
|---|---|---|---|---|---|
| Trastuzumab (Herceptin) | 2010 | First-line HER2-positive metastatic gastric/GEJ adenocarcinoma, with chemotherapy | ToGA (NCT01041404) | Overall survival (OS) | Median OS 13.8 vs 11.1 months with chemo alone (HR ~0.74); higher benefit in FISH+/IHC3+ subgroup |
| Ramucirumab (Cyramza) | 2014 | Previously treated advanced gastric/GEJ cancer (monotherapy or with paclitaxel) | REGARD; RAINBOW (with paclitaxel) | Overall survival (OS); PFS | REGARD OS 5.2 vs 3.8 months (HR 0.78, p=0.047); RAINBOW OS 9.6 vs 7.4 months (HR 0.81, p=0.017) |
| Pembrolizumab (Keytruda) | 2021 | First-line HER2-positive advanced gastric/GEJ cancer (with trastuzumab + chemo); MSI-H tumors | KEYNOTE-811 (HER2+); KEYNOTE-059 (earlier ORR data) | Objective response rate / overall survival | KEYNOTE-059 ORR 13.3% (PD-L1 CPS>=1); markedly higher ORR (~57%) in MSI-H tumors |
| Nivolumab (Opdivo) | 2021 | First-line advanced gastric/GEJ/esophageal adenocarcinoma, with chemotherapy | CheckMate-649 (NCT02872116) | Overall survival (OS) and PFS | OS 13.8 vs 11.6 months all-randomized (HR 0.80, p=0.0002); CPS>=5 OS 14.4 vs 11.1 months (HR 0.71) |
| Trastuzumab deruxtecan (Enhertu) | 2021 | HER2-positive advanced gastric/GEJ cancer after prior HER2-targeted therapy | DESTINY-Gastric01 (NCT03329690) | Objective response rate; overall survival | ORR 40.5% vs 11.3% chemo (p<0.0001); OS 12.5 vs 8.4 months (HR 0.59, p=0.0097) |
| Zolbetuximab (Vyloy) | 2024 | First-line CLDN18.2-positive, HER2-negative advanced gastric/GEJ adenocarcinoma, with chemotherapy | SPOTLIGHT (with mFOLFOX6); GLOW (with CAPOX) | Progression-free survival (PFS); OS | SPOTLIGHT PFS 10.6 vs 8.7 months (HR 0.75); GLOW PFS 8.2 vs 6.8 months (HR 0.69); both improved OS |
Where trials have failed
Drugs that missed their endpoint — and what contributed
The most instructive lessons in stomach (gastric) cancer development come from programmes that failed the endpoint that mattered.
| Drug / trial | Endpoint outcome | What contributed |
|---|---|---|
| Lapatinib — LOGiC / TyTAN (NCT00680901) | Failed to significantly improve overall survival in HER2-positive gastric cancer | HER2 inhibition alone insufficient; regional and biomarker heterogeneity in response |
| Trastuzumab emtansine (T-DM1) — GATSBY (NCT01641939) | Did not meet OS primary endpoint vs taxane in previously treated HER2-positive gastric cancer | ADC did not outperform chemotherapy; possible HER2 loss/heterogeneity after prior therapy |
| Regorafenib — INTEGRATE II (NCT01913639) | Multikinase inhibitor showed limited efficacy in advanced gastric cancer per whitepaper | Challenges of unselected multikinase inhibition without predictive biomarkers |
Choosing the right endpoint
Primary endpoints that matter in stomach (gastric) cancer trials
- Overall survival (OS) — Gold-standard primary endpoint; requires prolonged follow-up and is subject to attrition
- Progression-free survival (PFS) — Surrogate for efficacy; depends on standardized, centrally reviewed RECIST imaging
- Objective response rate (ORR) — Short-term tumor-shrinkage measure by RECIST v1.1; supports accelerated approvals
- Duration of response (DoR) — Captures durability of tumor response, important for ADCs and immunotherapy
- Biomarker-defined subgroups (HER2, PD-L1 CPS, CLDN18.2, MSI-H) — Essential stratification; expression heterogeneity strongly affects outcomes
How iNGENū runs stomach (gastric) 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
Stomach (Gastric) Cancer clinical trials — FAQs
What biomarkers guide gastric cancer treatment selection?
Why is zolbetuximab (Vyloy) significant?
What is the preferred primary endpoint in gastric cancer trials?
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