domvanalimab (AB154) / Arcus Biosci, Gilead, Otsuka - LARVOL DELTA

Domvanalimab (dom), zimberelimab (zim), and FOLFOX in first-line (1L) advanced gastric, gastroesophageal junction, or esophageal adenocarcinoma (GC/GEJC/EAC): 26-month update from EDGE-Gastric, arm A1 (ESMO 2025) - P2, P3 | "EDGE-Gastric (NCT05329766), Arm A1 evaluated the efficacy and safety of 1L dom (Fc-silent anti-TIGIT), zim (anti–PD-1), and FOLFOX (oxaliplatin, leucovorin, and fluorouracil) in patients (pts) with previously untreated advanced HER-2-negative GC/GEJC/EAC. The safety profile was consistent with that of anti–PD-1 + FOLFOX. The phase 3 STAR-221 trial (NCT05568095) comparing 1L dom + zim + chemotherapy vs nivolumab + chemotherapy in advanced GC/GEJC/EAC is fully enrolled."

Clinical • Metastases • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Oncology • Solid Tumor • HER-2 • PD-L1 • TIGIT

Imfinzi + domvanalimab: Data from P3 PACIFIC-8 trial (NCT05211895) for stage 3 NSCLC post 2027 (AstraZeneca) - FY 2025 Results

P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

STAR-121: Zimberelimab and Domvanalimab in Combination With Chemotherapy Versus Pembrolizumab With Chemotherapy in Patients With Untreated Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=1021 | Active, not recruiting | Sponsor: Gilead Sciences | Recruiting ➔ Active, not recruiting

Enrollment closed • IO biomarker • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • NTRK • PD-L1 • RET

STAR-121: Zimberelimab and Domvanalimab in Combination With Chemotherapy Versus Pembrolizumab With Chemotherapy in Patients With Untreated Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=1069 | Recruiting | Sponsor: Gilead Sciences | Trial completion date: Jun 2028 ➔ Jan 2029

IO biomarker • Trial completion date • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • NTRK • PD-L1 • RET

Phase 2 randomized study of domvanalimab combined with zimberelimab in front-line, PD-(L)1 high, locally advanced or metastatic non-small cell lung cancer (NSCLC): results from ARC-10 part 1 (SITC 2024) - P3 | "Ethics Approval At each site, the study was conducted in full accordance with the 21 Code of Federal Regulations, International Council for Harmonisation guidelines, institutional review board and independent ethics committee guidelines, and all other applicable local or regional regulations. All patients provided written informed consent before enrollment.View this table:View inline View popup Download powerpoint Abstract 1461 Table 1 ARC-10 study efficacy endpointsDownload figure Open in new tab Download powerpoint Abstract 1461 Figure 1 Kaplan-Meier estimate of progression-free survivalDownload figure Open in new tab Download powerpoint Abstract 1461 Figure 2 Kaplan-Meier estimate of overall survival"

Clinical • IO biomarker • Late-breaking abstract • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TIGIT

ARC-7: Randomized phase 2 study of domvanalimab + zimberelimab ± etrumadenant versus zimberelimab in first-line, metastatic, PD-L1-high non-small cell lung cancer (NSCLC). (ASCO Plenary Dec 2022) - P2 | "NCT04262856"

Clinical • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Switch Maintenance in Pancreatic (clinicaltrials.gov) - P1/2 | N=46 | Suspended | Sponsor: James Cleary, MD, PhD | Recruiting ➔ Suspended

Trial suspension • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma

Updates on Abstract 397600: ARC-7: Randomized phase 2 study of domvanalimab + zimberelimab ± etrumadenant versus zimberelimab in first-line, metastatic, PD-L1-high non-small cell lung cancer (NSCLC) (ASCO 2023) - No abstract available

Clinical • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Updates on Abstract 433248: EDGE-Gastric Arm A1: Phase 2 Study of Domvanalimab, Zimberelimab, and FOLFOX in First-Line (1L) Advanced Gastroesophageal Cancer (ASCO 2024) - No abstract available

Clinical • Metastases • P2 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Phase 3 trial of durvalumab combined with domvanalimab following concurrent chemoradiotherapy (cCRT) in patients with unresectable stage III NSCLC (PACIFIC-8). (ASCO 2023) - P2, P3 | "Previously presented at the European Society for Medical Oncology (ESMO) Congress 2022, FPN (Final Publication Number): 971TiP, Mustafa Özgüroğlu et al. – Reused with permission.Clinical trial information: NCT05211895."

Clinical • IO biomarker • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • NECTIN2 • PVR • TIGIT

EDGE-Gastric Arm A1: Phase 2 study of domvanalimab, zimberelimab, and FOLFOX in first-line (1L) advanced gastroesophageal cancer (ASCO Plenary Nov 2023) - P2 | "NCT05329766"

Clinical • Metastases • P2 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Trial of FOLFIRI + Zimberelimab + Domvanalimab vs FOLFIRI With a Hybrid Synthetic Control Arm in Second Line Treatment of Neuroendocrine Carcinoma of Gastro-enteropancreatic or Unknown Origin (REWENEC 01) (clinicaltrials.gov) - P2 | N=122 | Not yet recruiting | Sponsor: Hospices Civils de Lyon

New P2 trial • Endocrine Cancer • Gastrointestinal Neuroendocrine Carcinoma • Neuroendocrine Carcinoma • Oncology • Pancreatic Cancer • Solid Tumor

MODULE 4: Other Novel Agents and Strategies Under Evaluation for Advanced Gastroesophageal Cancers (ASCO-GI 2026) - "This event is organized and accredited by Research To Practice and supported by educational grants from Astellas, BeOne, Gilead Sciences Inc, and Jazz Pharmaceuticals Inc. Potential immunotherapy targets beyond PD-1/PD-L1 and CTLA-4 in gastroesophageal cancers; proposed rationale for targeting TIGIT Updated efficacy findings, including overall survival outcomes, documented with the combination of the anti-TIGIT monoclonal antibody domvanalimab, the anti-PD-1 antibody zimberelimab and chemotherapy as first-line therapy for advanced gastroesophageal adenocarcinoma in arm A1 of the EDGE-Gastric study Emerging outcomes from the Phase III STAR-221 trial comparing domvanalimab/zimberelimab/chemotherapy to nivolumab/chemotherapy for previously untreated advanced gastric, GEJ and esophageal adenocarcinoma Mechanism of action of and early findings with the PD-1/TIGIT bispecific antibody rilvegostomig for advanced gastroesophageal cancers Ongoing Phase III ARTEMIDE-Gastric01 study..."

Metastases • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • CLDN18 • HER-2 • TIGIT

AB154 Combined With AB122 for Recurrent Glioblastoma (clinicaltrials.gov) - P1 | N=46 | Active, not recruiting | Sponsor: Yale University | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Nov 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • IDH1

In the first quarter of 2026, Arcus and Gilead expect to conduct an analysis of STAR-121, a Phase 3 study evaluating domvanalimab plus zimberelimab and chemotherapy in 1L non-small cell lung cancer (Businesswire)

P3 data • Non Small Cell Lung Cancer

Zimberelimab + Domvanalimab in Gastroesophageal Adenocarcinoma (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Massachusetts General Hospital | Not yet recruiting ➔ Withdrawn

Trial withdrawal • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Oncology • Solid Tumor

Zimberelimab + Domvanalimab in Gastroesophageal Adenocarcinoma (clinicaltrials.gov) - P2 | N=28 | Not yet recruiting | Sponsor: Massachusetts General Hospital

New P2 trial • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Cancer • Oncology • Solid Tumor

Arcus Provides Update on Phase 3 STAR-221 Study... (Arcus Biosciences Press Release) - "Arcus Biosciences...announced the discontinuation of the Phase 3 STAR-221 study, being conducted in partnership with Gilead Sciences, Inc., due to futility. The decision is based on the recommendation from the Independent Data Monitoring Committee (IDMC) following its review of data from an event-driven, pre-specified interim analysis of overall survival (OS)...At the interim analysis, the domvanalimab-based combination did not improve OS relative to that of nivolumab plus chemotherapy. The safety profile for the domvanalimab-based combination was similar to that of nivolumab plus chemotherapy, and there were no new safety findings identified....The STAR-221 and the Phase 2 EDGE-Gastric studies will be discontinued..."

DSMB • P3 data • Trial termination • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma

Safety and Efficacy of Zimberelimab (AB122) in Combination With Domvanalimab (AB154) and Etrumadenant (AB928) in Patients With Previously Treated Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Dec 2029 ➔ Jun 2030 | Trial primary completion date: Oct 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

A Pilot Study to Evaluate the Combination of Zimberelimab, Domvanalimab and Etrumadenant in Patients with Previously Treated Non-Small Cell Lung Cancer (NSCLC) (SITC 2025) - "Biomarker analyses are planned.Trial Registration NCT04791839Ethics Approval The study was conducted in accordance with the International Conference on Harmonization Good Clinical Practice (ICH GCP) and approved by the Washington University Human Research Protection Office (IRB ID #: 202104122). All participants signed informed consent before taking part on the study."

Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TIGIT

STAR-221: A Clinical Trial of a New Combination Treatment, Domvanalimab and Zimberelimab, Plus Chemotherapy, for People With an Upper Gastrointestinal Tract Cancer That Cannot be Removed With Surgery That Has Spread to Other Parts of the Body (clinicaltrials.gov) - P3 | N=1040 | Active, not recruiting | Sponsor: Arcus Biosciences, Inc. | Trial completion date: Feb 2027 ➔ Jun 2026 | Trial primary completion date: Dec 2026 ➔ Jun 2026

Trial completion date • Trial primary completion date • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor

IMMUNORARE5: A national platform of 5 academic phase II trials coordinated by Lyon University Hospital to assess the safety and the efficacy of the immunotherapy (domvanalimab + zimberelimab) in patients with advanced rare cancers: The neuroendocrine tumors cohort (ESMO 2025) - P2 | "Background Five drugs are approved for pancreatic NETs (everolimus, sunitinib, chemotherapy, somatostatin analogues, and peptide receptor radionuclide treatment (PRRT)), two for gastrointestinal NETs (everolimus and PRRT) and one for thoracic NETs (everolimus)...Increased TIGIT expression in high-grade NETs after pembrolizumab supports combining anti-TIGIT with ICI. Oxaliplatin-based regimens represent a standard treatment for advanced GEP and thoracic NET, as an alternative to alkylating agents...Legal entity responsible for the study B. You. Funding Gilead Company."

Clinical • IO biomarker • Metastases • P2 data • Neuroendocrine Tumor • Oncology • Solid Tumor • TIGIT

Domvanalimab plus zimberelimab shows promise in upper-tract cancers. (PubMed, Nat Rev Clin Oncol) - No abstract available

Journal • Oncology

Zimberelimab + domvanalimab: Completion of P3 STAR-221 trial (NCT05568095) for upper gastrointestinal tract cancer in Feb 2027 (Otsuka) - Q3 FY2025 Results

Trial completion date • Gastrointestinal Cancer • Oncology

Phase II study of sacituzumab govitecan (SG), domvanalimab (dom), and zimberelimab (zim) in metastatic non-small cell lung cancer (mNSCLC): VELOCITY-Lung substudy-01 (ESMO 2025) - P2 | "Conclusions SG+dom+zim had a tolerable safety profile and activity in 1L mNSCLC irrespective of histology and notably in pts with tumors expressing PD-L1. Further study of this combination is warranted, especially in pts with mNSLC with PD-L1 expression ≥50%."

IO biomarker • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1 • TIGIT