LBA79
Zanidatamab (zani) + chemotherapy (CT) ± tislelizumab (TIS) for first-line (1L) HER2-positive (HER2+) advanced/metastatic gastroesophageal adenocarcinoma (mGEA): Second interim analysis (IA) from HERIZON-GEA-01
https://esmocongress.esmo.org
ESMO Congress 2026
October 23–27, 2026 · Madrid · 2818 items
HERIZON-GEA
★★★Late-breaking11 people · 12 posts · 1 abstract
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Heat now 4·Peak in the comparable set 6 (Oct 24 03:00)·Change over 24h in the comparable set –·Participants now 10
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Deep dive
HERIZON-GEA-01 is a global, open-label phase III trial evaluating zanidatamab (a HER2 bispecific antibody) plus chemotherapy with or without tislelizumab (anti-PD-1) versus standard trastuzumab plus chemotherapy for first-line HER2-positive advanced gastroesophageal adenocarcinoma [1]. The primary analysis published in NEJM (median follow-up 25.9 months) confirmed significant PFS benefit for both doublet and triplet arms (median PFS 12.4 months each vs 8.1 months, HR 0.63 and 0.65) [2], while a phase Ib/II study showed the triplet achieved ORR 75.8% and median OS 32.4 months [3].
At ESMO 2026, the second interim analysis (LBA79, median follow-up 35.3 months, 914 patients) reported OS outcomes. Zani+chemo vs Tras+chemo: median OS 22.9 vs 19.6 months, HR 0.76, p=0.0088 (statistically significant). Zani+Tis+chemo vs Tras+chemo: median OS 27.0 vs 19.6 months, HR 0.65. Direct triplet vs doublet comparison: median OS 27.0 vs 22.9 months, HR 0.81, p=0.0502 (missed significance). Three-year OS rates were 39.8%, 31.5%, and 22.9% respectively [conference posts].
This establishes a statistically significant OS win for the zanidatamab doublet over trastuzumab standard. Although the triplet missed statistical significance versus the doublet (p=0.0502), the 4-month median OS gain, near 40% three-year OS rate, longer treatment duration (~47 vs ~30 weeks), and no new safety signals support a clinically meaningful trend [conference posts]. A pooled analysis also suggested triplet median OS of 27.0 months and PFS advantage over pembrolizumab-based regimens [6].
Limitations include the lack of statistical significance for triplet vs doublet OS, open-label design, and absence of direct head-to-head comparison with current immuno-chemotherapy standards (e.g., KEYNOTE-811), leaving the optimal partner regimen to be further defined.
References
- 1.HERIZON-GEA-01: Zanidatamab + chemo ± tislelizumab for 1L treatment of HER2-positive gastroesophageal adenocarcinoma · Future Oncol 2022
- 2.Zanidatamab with and without Tislelizumab in HER2-Positive Gastroesophageal Cancer · N Engl J Med 2026
- 3.Phase Ib/II Study of Zanidatamab in Combination with Tislelizumab and Chemotherapy in First-Line HER2-Positive Gastric/Gastroesophageal Junction Adenocarcinoma · Clin Cancer Res 2026
- 4.Reprogramming HER2-Positive gastroesophageal cancer immune contexture with bispecific therapy: HERIZON-GEA-01 · Med 2026
- 5.Redefining First-Line HER2-Positive Advanced Gastric Cancer: From Trastuzumab-Based Chemoimmunotherapy to Zanidatamab and Next-Generation HER2 Targeting · J Gastrointest Cancer 2026
- 6.Zanidatamab vs trastuzumab with or without PD-1 blockade in HER2-positive metastatic gastric cancer: a reconstructed patient-level pooled analysis · Oncologist 2026
Evidence
Floor
Erman Akkus@Erman_Akkus 🚀Upper GI oral abstracts #ESMO26 Day 1 summary results
★★★Same topic HERIZON-GEA · 11 peopleSANOtavatecanpembrolizumabdaraxonrasibanbenitamabtrastuzumabbemotrizumabdostarlimab2498 views36 likes24 reposts0 repliesAya Mohamed | MSc, MD 🎗@Dr_Oncologista ★★★Same topic HERIZON-GEA · 11 peoplezanidatamabtrastuzumabtislelizumabHER2#HER2POSITIVE872 views18 likes5 reposts1 replyArndt Vogel@ArndtVogel Zanidatamab + CT ± tislelizumab for 1L HER2-positive mGEA: Second IA from HERIZON-GEA-01
DaisukeKotani@DaisukeKotani DaisukeKotani@DaisukeKotani Nicholas Hornstein@GIMedOnc HERIZON-GEA-01 second OS interim at #ESMO26, and I'm a triplet believer.
Nieves Martinez Lago MD PhD@DraMartinezLago #ESMO26 🧬 HERIZON-GEA-01 | Phase III
BeOne Medical Affairs@BeOneMedAffairs ScienceLink@sciencelinkonco #ScienceLink #Madrid2026 #ESMO26 #HERIZONGEA01 #Zanidatamab
Same topic HERIZON-GEA · 11 peoplezanidatamabtrastuzumabtislelizumabHER2#SCIENCELINK#MADRID2026#HERIZONGEA01#ZANIDATAMAB82 views1 like0 reposts0 repliesmp.weixin.qq.com HERIZON-GEA-01 Phase 3: Zanidatamab Plus Tislelizumab and Chemotherapy Lifts Median OS to 27.0 Months in First-Line HER2-Positive Advanced Gastric Cancer
In the HERIZON-GEA-01 study, the zanidatamab plus tislelizumab plus chemotherapy arm achieved a median overall survival of 27.0 months in HER2-positive advanced gastroesophageal adenocarcinoma, with HR=0.65. The global multicenter phase 3 trial reported this second interim OS analysis after a median follow-up of 35.3 months; median OS was 19.6 months in the control arm and 22.9 months in the zanidatamab plus chemotherapy arm, HR=0.76, P=0.0088.
mp.weixin.qq.comPick BeiGene HERIZON-GEA-01: Zanidatamab Plus Tislelizumab and Chemo Extends OS in HER2-Positive Gastroesophageal Adenocarcinoma, Difference Versus Zanidatamab Plus Chemo Not Significant
In the Phase 3 HERIZON-GEA-01 trial from BeiGene, zanidatamab combined with tislelizumab and chemotherapy as first-line treatment for HER2-positive gastroesophageal adenocarcinoma achieved a median overall survival of 27.0 months. The difference versus the zanidatamab plus chemotherapy group did not reach statistical significance.
Why it matters: OS and PFS data at 35.3 months of follow-up, with HR, confidence interval and stratified results, allow direct comparison with trastuzumab plus chemotherapy.