HERIZON-GEA-01 Trial

[Slide 1] HERIZON-GEA-01 Discussion - ASCO GI 2026 (#GI26), presented by Elena Elimova, MD. HERIZON-GEA-01 is the first phase 3 study in mGEA to demonstrate a median PFS >1 year and a median OS >2 years. These findings support zanidatamab as a promising new standard in HER2-targeting agents, with potential to replace trastuzumab in first-line treatments for HER2+ mGEA. The clinically meaningful survival benefit further supports zanidatamab plus tislelizumab and CT as an important new treatment option for this patient population. Treatment with zanidatamab-containing regimens led to a clinically meaningful prolongation of PFS that was statistically superior to trastuzumab + CT (>4-month prolongation of median PFS). Zanidatamab + tislelizumab + CT demonstrated a clinically meaningful and statistically superior prolongation of OS vs trastuzumab + CT (>7-month prolongation of median OS). At this interim analysis, there was a strong trend toward statistical significance for OS favoring zanidatamab + CT vs trastuzumab + CT (5-month improvement in median OS); the trial is ongoing with additional OS analyses planned for zanidatamab + CT. The PFS and OS benefits were generally observed across key prespecified subgroups, including in patients with PD-L1 TAP scores <1% and >=1%. The safety profile was consistent with the known profiles of each individual treatment; for patients who experienced diarrhea, events generally occurred early in treatment and resolved within 3 weeks.

HERIZON-GEA-01 — Health-Related Quality of Life (HRQoL), ESMO GI 2026 (Abstract 494O), presented by Kohei Shitara. Key findings reported from these slides (source: OncoDaily ESMO GI 2026 congress coverage and presenter-shared slides): - EORTC QLQ-C30 questionnaire completion exceeded 95% through cycle 34 day 1 across all arms. - Physical functioning: mean baseline scores 81.5-83.5 across arms; at cycle 2, reductions were slightly larger with zanidatamab-containing regimens vs trastuzumab but differences remained small; most patients maintained or improved physical functioning from baseline between cycles 2 and 8. - Global Health Status/QoL: changes from baseline were numerically similar across the three arms, with no substantive changes over time. - Symptom scales: diarrhea (the most common treatment-related AE in the zanidatamab arms) showed the greatest worsening from baseline at cycle 8 day 1, consistent with the trial's established safety profile. Note: this ESMO GI 2026 HRQoL analysis is descriptive/supportive; efficacy figures (PFS 12.4 vs 8.1 mo; OS 26.4 vs 19.2 mo) are from the ASCO GI 2026 primary readout (DCO 1-Oct-2025). Both regimens received FDA approval in 1L HER2+ GEA on Aug 25, 2026.

[Slide 1] HERIZON-GEA-01: Overall Survival (interim) - discussant slide (ASCO GI 2026 #GI26, presented by Daniel Lin, MD, MSc). Putting into the context of current standard: HERIZON-GEA-01 (n=914) vs KEYNOTE-811 (n=698; Janjigian et al, Ann Oncol 2024;35(Suppl):S877-S878). HERIZON-GEA-01 (overall population): Zani+TIS+CT vs Tras+CT - OS 26.4 vs 19.2 mo (HR 0.72), PFS 12.4 vs 8.1 mo (HR 0.63); Zani+CT vs Tras+CT - OS 24.4 vs 19.2 mo (HR 0.80), PFS 12.4 vs 8.1 mo (HR 0.65). KEYNOTE-811 (Tras+Pembro+CT vs Tras+CT): overall - OS 20.0 vs 16.8 mo (HR 0.80), PFS 10.0 vs 8.1 mo (HR 0.73); PD-L1 CPS >=1 - OS 20.1 vs 15.7 mo (HR 0.79), PFS 10.9 vs 7.3 mo (HR 0.72). Notable OS improvement with trastuzumab + CT vs historical benchmarks - multidisciplinary care? subsequent therapies? regional differences?

[Slide 1] HER2+ Gastric Cancer breaks the OS barrier @DrRishabhOnco HERIZON-GEA-01 I Phase III I # GI26 First clear frontline OS win in a decade Who & What Phase III, n=914 1L HER2+ metastatic GEA Global trial Treatment arms Trastuzumab Zanidatamab Zanidatamab + + chemo + chemo chemo + tislelizumab PFS 8.1 12.4 months ~35% lower progression risk 26.4 Median OS 26.4 months ~28% lower risk of death Benefit across MO regions ~54% alive at 2 years Independent of PD-L1 ! Safety Higher toxicity with triplet Clinical takeaway: No new safety signals Dual HER2 targeting + PD-1 is poised to replace trastuzumab Save for clinic as 1L standard in HER2+ mGEA

[Slides 1-2] HERIZON-GEA-01 - Primary Endpoint: Overall Survival (ASCO GI 2026 #GI26, presented by Elena Elimova, MD; photographed in-hall). Zanidatamab + tislelizumab + CT demonstrated a statistically significant and clinically meaningful OS benefit with a >7-month improvement in median OS vs trastuzumab + CT. Median OS 26.4 months (95% CI 21.5-30.3) vs 19.2 months (95% CI 16.8-21.8); HR 0.72 (95% CI 0.57-0.90), P=0.0043. Landmark OS: 24-month 54.3% (95% CI 47.6-60.5) vs 38.8% (95% CI 32.2-45.4); 30-month 43.8% (95% CI 36.5-50.9) vs 30.0% (95% CI 23.4-36.8). Patients at risk (0-48 mo, 3-mo intervals): Zani+TIS+CT 302, 267, 246, 222, 190, 157, 125, 96, 82, 64, 49, 36, 27, 10, 4, 2, 0; Tras+CT 308, 284, 261, 219, 178, 140, 106, 77, 61, 50, 33, 22, 17, 8, 2, 2, 0.

[Slide 1] HERIZON DEA-301 HERIZON-GEA-01 Study Design Global phase 3 trial of zanidatamab + chemotherapy ± tislelizumab VS trastuzumab + chemotherapy in previously untreated patients with HER2+ mGEA Key Eligibility Criteria Arm A: Trastuzumab + Age >18 years chemotherapy Unresectable, locally advanced, Dual Primary Endpoints recurrent or metastatic GEA PFS (per BICR) HER2 IHC 3+ or IHC 2+/ISH+ R Arm B: Zanidatamab OS per central testing 1:1:1 1800 mg (<70 kg)/2400 mg (270 kg) IV Q3W ECOG PS 0 or 1 + chemotherapy* CT/MRI Select Secondary Endpoints Q6W No prior treatment for locally advanced N = 914 cORR (per BICR) or metastatic disease Frequency and severity of AEs No prior HER2-targeted agents or Arm C: Zanidatamab immunotherapy in any setting 1800 mg (<70 kg)/2400 mg (270 kg) IV Q3W ClinicalTrials.gov: NCT05152147 + tislelizumabᵇ + chemotherapya Stratification Factors Prophylaxis to prevent IRR and diarrhea was Geographic region mandatory in the zanidatamab-containing arms HER2 status ECOG PS Treatment until disease progression/death/unacceptable toxicity Chemotherapy could be discontinued after 6 cycles Physician's choice of capecitabine plus oxaliplatin or 5 Sucrouracil plus cisplatin Chemotherapy was administered for at least 6 cycles or until disease progression, unacceptable toxicity, or another criterion for treatment discontinuation was met *Tislelizumab 200 mg was administered IV Q3W CT/MRI scans were performed every 6 weeks for the first 54 weeks, then every wooks AE, adverse event, BICR binded independent contral review, CORR, confirmed objective response rate, CT, computed tomography ECOG PS, Eastern Cooperative Oncology Group performance status, GEA, gastroesophageal adenocarcinoma, HER2, human epidermal growth factor receptor 2. IHC, immunohistochemistry, IRR, infusion related reaction; ISH, in situ hybridization, IV, intravenously, mGEA, advanced or metastatic GEA MRI, magnetic resonance imaging OS, overall survival PFS, progression free survival, Q3W, every 3 weeks, Q6W. every 6 weeks, R. randomization ASCO Gastrointestinal #GI26 PRESENTED BY Elena Elimova, MD ASCO - ENCOLOGY Cancers Symposium Presentation property of the author and ASCO Permission required for - contact permissions@asco.org KNOWLEDGE CONQUERS CANCER