Gastric · GC

mOS 9.2 vs 8.6 mo (HR 0.77, p=0.02); TTP 5.6 vs 3.7 mo; ORR 37% vs 25%; 2-yr OS 18% vs 9%; grade 3-4 neutropenia 82%

Population: Advanced gastric cancer receiving first-line therapy

Capecitabine noninferior to 5FU (HR 0.86); oxaliplatin noninferior to cisplatin (HR 0.92); EOX best arm mOS 11.2 mo vs ECF 9.9 mo (HR 0.80, p=0.02)

Population: Advanced esophagogastric cancer

mOS 13.0 vs 11.0 mo (HR 0.77, 95% CI 0.61-0.98, p=0.04); mPFS 6.0 vs 4.0 mo (HR 0.57); ORR 54% vs 31%

Population: Japanese patients with advanced gastric cancer receiving first-line therapy

mOS 14.1 vs 13.1 mo; PFS HR 1.004 (noninferior); SOX fewer grade>=3 AEs (less renal, less neutropenia)

Population: Japanese chemotherapy-naive advanced gastric cancer

Pembro vs chemo (CPS>=1) mOS 10.6 vs 11.1 mo noninferior; CPS>=10 17.4 vs 10.8 mo (HR 0.69 NS); pembro+chemo vs chemo NS on OS

Population: First-line PD-L1 CPS>=1 advanced gastric/GEJ adenocarcinoma

PD-L1 CPS>=5: mOS 14.4 vs 11.1 mo (HR 0.71, 98.4% CI 0.59-0.86, p<0.0001); mPFS 7.7 vs 6.0 mo (HR 0.68); ORR 60% vs 45%; primary endpoint met

Population: HER2-negative advanced gastric, GEJ, or esophageal adenocarcinoma as first-line therapy

mOS 10.4 vs 10.9 mo (HR 0.91, 95% CI 0.74-1.11, p=0.178, NEGATIVE); 24-mo OS 22.1% vs 15.5%; TRAE grade>=3 12.8% vs 32.8%

Population: HER2-negative advanced gastric cancer without progression after 12 weeks of induction chemotherapy

mPFS 10.45 vs 8.34 mo (HR 0.68, 98.51% CI 0.51-0.90, p=0.0007); mOS 17.45 vs 17.15 mo (HR 0.90, p=0.26, primary OS endpoint NOT met)

Population: East Asian patients with HER2-negative advanced gastric/GEJ cancer as first-line therapy

ITT mOS 12.9 vs 11.5 mo (HR 0.78, 95% CI 0.70-0.87, p<0.0001); CPS>=10 HR 0.65; mPFS 6.9 vs 5.6 mo (HR 0.76); ORR 51.3% vs 42.0%

Population: HER2-negative advanced gastric/GEJ adenocarcinoma as first-line therapy

All-comers mOS 15.2 vs 12.3 mo (HR 0.77, 95% CI 0.63-0.94, p=0.009); CPS>=5 mOS 18.4 vs 12.9 mo (HR 0.66, 95% CI 0.50-0.86, p=0.002)

Population: Chinese patients with HER2-negative advanced gastric/GEJ adenocarcinoma as first-line therapy

PD-L1 TAP>=5%: mOS 17.2 vs 12.6 mo (HR 0.74); ITT mOS 15.0 vs 12.9 mo (HR 0.80, p=0.001); safety similar

Population: HER2-negative advanced gastric/GEJ adenocarcinoma as first-line therapy

mOS 13.8 vs 11.1 mo (HR 0.74, 95% CI 0.60-0.91, p=0.0046); IHC3+/FISH+ subset mOS 16.0 vs 11.8 mo (HR 0.65)

Population: HER2-positive advanced gastric/GEJ cancer as first-line therapy

mOS 12.2 vs 10.5 mo (HR 0.91, NS, NEGATIVE); mPFS 6.0 vs 5.4 mo (HR 0.82, p=0.0381); ORR 53% vs 39%

Population: HER2-positive advanced gastroesophageal adenocarcinoma as first-line therapy

ORR 51% vs 14% (p<0.001); mOS 12.5 vs 8.4 mo (HR 0.59, 95% CI 0.39-0.88, p=0.01); ILD 9 grade 1-2, 3 grade 3-4

Population: Japanese/Korean HER2-positive advanced gastric/GEJ cancer progressing after >=2 lines including trastuzumab

Confirmed ORR 42% (95% CI 30.8-53.4); mPFS 5.6 mo; mOS 12.1 mo; ILD 10% (1 grade 5)

Population: Western HER2-positive gastric/GEJ cancer progressing on trastuzumab-containing regimen (2L)

mPFS 10.0 vs 8.1 mo (HR 0.72, 95% CI 0.60-0.87, p=0.0002); mOS 20.0 vs 16.8 mo (HR 0.84); ORR 72.6% vs 60.1%

Population: HER2-positive advanced gastric/GEJ cancer as first-line therapy

mOS 14.7 vs 11.4 mo (HR 0.70, 95% CI 0.55-0.90, p=0.004); mPFS HR 0.74; confirmed ORR 44.3% vs 29.1%

Population: HER2-positive gastric/GEJ cancer progressing on trastuzumab-based first-line therapy (re-biopsy-confirmed HER2+)

Topline 2025: both zani arms PFS HR ~0.65 vs control; zani+tisle+chemo mOS >7 mo improvement vs trastuzumab+chemo; ESMO 2025 LBA; full peer-reviewed results pending 2026

Population: HER2-positive advanced gastric/GEJ adenocarcinoma as first-line therapy

mPFS/mOS HRs 0.44 and 0.55 (both p<0.0005); subgroup with >=70% moderate/strong CLDN18.2 PFS HR 0.38

Population: CLDN18.2-positive advanced G/GEJ adenocarcinoma as first-line therapy

mPFS 8.21 vs 6.80 mo (HR 0.687, 95% CI 0.544-0.866, p=0.0007); mOS 14.39 vs 12.16 mo (HR 0.771, 95% CI 0.615-0.965, p=0.0118)

Population: CLDN18.2-positive HER2-negative advanced gastric/GEJ cancer as first-line therapy

1L+chemo mPFS 17.8 mo, ORR 71.4%; monotherapy 3L+ ORR 0%, mPFS 1.54 mo; zolbetuximab+pembro 3L+ ORR 0%, mPFS 2.96 mo

Population: CLDN18.2-positive advanced G/GEJ adenocarcinoma across late-line (1A, 3A) and first-line (Cohort 2) cohorts

mPFS 10.61 vs 8.67 mo (HR 0.75, 95% CI 0.60-0.94, p=0.0066); mOS 18.23 vs 15.54 mo (HR 0.75, 95% CI 0.60-0.94, p=0.0053)

Population: CLDN18.2-positive (>=75% cells IHC 2+/3+) HER2-negative advanced gastric/GEJ cancer as first-line therapy

High/medium CLDN18.2 any PD-L1: mPFS 12.6 mo; subset CPS<5 mPFS 12.6 mo; ORR 66%+

Population: First-line advanced G/GEJ cancer with high/medium CLDN18.2 expression

mPFS 3.25 vs 1.77 mo (HR 0.37, 95% CI 0.25-0.55, p<0.0001); ORR 37% vs 10%; mOS trend favorable (data maturing)

Population: CLDN18.2-positive (IHC >=2+, >=40% cells) advanced G/GEJ cancer refractory to >=2 prior lines

mOS 5.2 vs 3.6 mo (HR 0.67, 95% CI 0.49-0.92, p=0.01); improved symptom control (pain, nausea)

Population: Platinum/fluoropyrimidine-refractory oesophagogastric adenocarcinoma

mOS 9.6 vs 7.4 mo (HR 0.807, 95% CI 0.678-0.962, p=0.017); mPFS 4.4 vs 2.9 mo (HR 0.635, p<0.0001); ORR 28% vs 16%

Population: Advanced gastric/GEJ adenocarcinoma progressing on first-line platinum/fluoropyrimidine

mOS 5.2 vs 3.8 mo (HR 0.776, 95% CI 0.603-0.998, p=0.047); mPFS 2.1 vs 1.3 mo (HR 0.483, p<0.0001)

Population: Advanced gastric/GEJ adenocarcinoma after first-line platinum/fluoropyrimidine

mOS 5.26 vs 4.14 mo (HR 0.63, 95% CI 0.51-0.78, p<0.0001); 12-mo OS 26.2% vs 10.9%; ORR 11.2% vs 0%

Population: East Asian patients with advanced gastric/GEJ cancer after >=2 prior lines of therapy

ORR: nivo 12% / nivo1+ipi3 24% / nivo3+ipi1 8%; 12-mo OS 39% / 35% / 24%

Population: Western patients with chemotherapy-refractory gastric, esophageal, or GEJ cancer (79% with >=2 prior lines)

CPS>=1 mOS 9.1 vs 8.3 mo (HR 0.82, 95% CI 0.66-1.03, p=0.0421 NS, NEGATIVE); CPS>=10 signal of benefit; grade>=3 TRAE 14% vs 35%

Population: Advanced G/GEJ adenocarcinoma with PD-L1 CPS>=1 progressing after first-line platinum/fluoropyrimidine

mOS 5.7 vs 3.6 mo (HR 0.69, 95% CI 0.56-0.85, p=0.00058); mPFS HR 0.57

Population: Advanced gastric/GEJ cancer progressing after >=2 prior regimens (3L+)

mPFS 5.6 vs 2.7 mo (HR 0.57, p<0.0001, MET); mOS 9.6 vs 8.4 mo (HR 0.96, p=0.6064, NOT MET); ORR 42.4% vs 22.4%

Population: Chinese patients with advanced G/GEJ adenocarcinoma progressing after first-line platinum and fluoropyrimidine

mOS 36 vs 27 mo (HR for death 1.35, 95% CI 1.09-1.66, P=0.005); mRFS 30 vs 19 mo (HR 1.52); 3y OS 50% vs 41%

Population: Resected stomach or GEJ adenocarcinoma

5y OS 36% vs 23% (HR 0.75, 95% CI 0.60-0.93, P=0.009); PFS HR 0.66 (95% CI 0.53-0.81, P<0.001)

Population: Resectable adenocarcinoma of stomach, EGJ, or lower esophagus

3y OS 80.1% vs 70.1% (HR for death 0.68, 95% CI 0.52-0.87, P=0.003); 5y OS 71.7% vs 61.1% in long-term f/u (HR 0.669)

Population: Japanese patients with stage II/III gastric cancer after curative D2 gastrectomy

3y DFS 74% vs 59% (HR 0.56, 95% CI 0.44-0.72, p<0.0001); 5y OS 78% vs 69% (HR 0.66) per long-term follow-up

Population: Stage II-IIIB gastric cancer after D2 gastrectomy (Korea/China/Taiwan)

3y DFS 78.2% (XPRT) vs 74.2% (XP), HR 0.740 (95% CI 0.520-1.050, P=0.0922, NS); OS HR 1.130 (NS); subgroup benefit in node+ and intestinal Lauren

Population: D2-resected gastric cancer

3y OS 50.3% vs 48.1% (HR 1.08, 95% CI 0.91-1.29, p=0.36); anastomotic leak after oesophagogastrectomy 24% vs 10% on bev arm

Population: Resectable gastric, GEJ, or lower oesophageal adenocarcinoma

mOS 43 vs 37 mo (HR 1.01, 95% CI 0.84-1.22, p=0.90); 5y OS similar; postop compliance 59%/62%

Population: Stage IB-IVA resectable gastric/GEJ cancer

mOS 50 vs 35 mo (HR 0.77, 95% CI 0.63-0.94); pCR 16% vs 6%

Population: Locally advanced resectable gastric/GEJ adenocarcinoma (cT2+ or cN+)

3y RFS 66% vs 50% (HR 0.632, 99.99% CI 0.400-0.998, P<0.001); substantially higher neutropenia in doublet

Population: Stage III gastric cancer after R0 resection (Asian population)

3y DFS 64.8% (S-1) vs 74.3% (SOX, HR 0.692, P=0.042) vs 72.8% (SOXRT, HR 0.724, P=0.074); SOX vs SOXRT no difference (HR 0.971)

Population: D2-resected stage II/III node-positive gastric cancer

Adjusted PFS HR 0.70 (95% CI 0.52-0.95, P=0.023) for neoadj DOS+surgery+adj S-1 vs surgery+adj S-1; 3-yr PFS 66.3% vs 60.2%

Population: Korean patients with cT2-3N+ or T4 locally advanced gastric cancer

3y DFS 59.4% (periop-SOX) vs 51.1% (adj-CapOx), HR 0.77 (95% CI 0.61-0.97, p=0.028); adj-SOX 56.5% non-inferior to adj-CapOx

Population: Chinese patients with cT4aN+ or cT4bNany M0 gastric/GEJ cancer after D2 gastrectomy

3y RFS 68.4% vs 65.3% (HR 0.90, 95.72% CI 0.69-1.18, p=0.44); negative for adj IO in Asian stage III G/GEJ after D2

Population: Asian patients with stage III gastric/GEJ cancer after D2+ gastrectomy

pCR 17% vs 8% favoring CRT; median OS 46 vs 49 mo (HR 1.05, 95% CI 0.83-1.31, NS); mPFS 31 vs 32 mo (NS)

Population: Resectable stomach or GEJ adenocarcinoma

Main cohort: mOS 71.8 vs 55.7 mo (HR 0.86, 95% CI 0.71-1.06, NS); EFS HR 0.81 (95% CI 0.67-0.98); pathCR improved

Population: Treatment-naive locally advanced resectable gastric/GEJ cancer

2y EFS 67.4% vs 58.5% (HR 0.71, 95% CI 0.58-0.86, P<0.001); pCR 19.2% vs 7.2% (RR 2.69); 2y OS 75.7% vs 70.4%

Population: Resectable gastric/GEJ adenocarcinoma

5y OS 69.2% (D2) vs 70.3% (D2+PAND); HR 1.03 (95% CI 0.77-1.37, P=0.85); op time +63 min, blood loss +230 ml for PAND

Population: Japanese patients with curable T2b/T3/T4 gastric cancer

mOS 49.4 vs 24.0 mo (HR 0.657, 95% CI 0.495-0.871, P=0.003); R0 92% vs 69%; pCR 29% (overall), 23% (adenoca), 49% (SCC)

Population: Resectable esophageal or EGJ cancer (75% adenocarcinoma, 23% SCC)

3y DFS 76.5% (LDG) vs 77.8% (ODG), diff -1.3pp within noninf margin; 3y OS 83.1% vs 85.2% (HR 1.19, P=0.28, NS)

Population: Chinese patients with cT2-T4a locally advanced gastric cancer (without bulky nodes or metastases)

5y OS 94.2% (LDG) vs 93.3% (ODG, log-rank P=0.64); 5y cancer-specific survival 97.1% vs 97.2%; noninferiority met

Population: Korean patients with stage I gastric cancer

mDFS 22.4 vs 11.0 mo (HR 0.69, 96.4% CI 0.56-0.86, P<0.001); OS signal later mature (restricted to PD-L1+, non-sig ITT at ASCO 2025)

Population: R0 resected stage II/III esophageal/GEJ cancer with residual pathologic disease after neoadjuvant chemoradiotherapy

Median LOS 7 days both (P=0.34); LG lower blood loss (150 vs 300 ml); postop complications 44% vs 42% (NS); 1y OS 76% vs 78%; R0 95% both

Population: Resectable (cT1-4aN0-3bM0) gastric cancer in a Western (Dutch) population

5y OS 74.9% (bursectomy) vs 76.5% (omentectomy), HR 1.03 (95% CI 0.83-1.27, P=0.598); more intra-abdominal abscess with bursectomy (5.5% vs 2.5%)

Population: cT3-T4a gastric cancer

5y OS 88.9% (LDG) vs 88.7% (ODG); 5y RFS 79.5% vs 81.1% (NS); late complications 6.5% vs 11.0% favoring LDG

Population: Locally advanced gastric cancer after R0 resection

5y RFS 73.9% (ODG) vs 75.7% (LADG); HR 0.96 (90% CI 0.72-1.26, noninferiority P=0.03); 5y OS HR 0.83 (NS)

Population: Japanese patients with locally advanced gastric cancer

mOS 48 vs 49.2 mo (HR 1.03, 95% CI 0.77-1.38, p=0.82); 3y OS 55% vs 57%; pCR + R0 favored CRT; DFS HR 0.89 (NS)

Population: Locally advanced resectable oesophageal or EGJ adenocarcinoma