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

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

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

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 | Completed | Sponsor: Arcus Biosciences, Inc. | Active, not recruiting ➔ Completed

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

STAR-221: A phase III study of first-line (1L) domvanalimab (D), zimberelimab (Z), and chemotherapy (chemo) vs nivolumab (N) + chemo in advanced HER2-negative gastric, gastroesophageal junction, or esophageal adenocarcinoma (GC/GEJC/EAC) (ESMO-GI 2026) - P3 | "No new safety findings were identified. Table: 493O"

Clinical • Metastases • P3 data • Esophageal Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • TIGIT

VELOCITY-HNSCC: Study of Novel Treatment Combination Therapies in Participants With Head and Neck Squamous Cell Carcinoma Regardless of PD-L1 Expression Status; Substudy-01 (clinicaltrials.gov) - P2 | N=39 | Active, not recruiting | Sponsor: Gilead Sciences | N=100 ➔ 39 | Trial completion date: Aug 2026 ➔ Mar 2027 | Trial primary completion date: Aug 2026 ➔ Mar 2027

Enrollment change • IO biomarker • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • 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

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

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

ZODIAC: Zimberelimab Anti-PD1 +/- Domvanalimab in Resectable Mmrd Gastric Cancer (clinicaltrials.gov) - P2 | N=50 | Suspended | Sponsor: Royal Marsden NHS Foundation Trust | Recruiting ➔ Suspended

dMMR • Mismatch repair • Trial suspension • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Microsatellite Instability • Oncology • Solid Tumor • MLH1 • MSH2 • MSH6 • MSI

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

PACIFIC-8: A Global Study to Assess the Effects of Durvalumab + Domvanalimab Following Concurrent Chemoradiation in Participants With Stage III Unresectable NSCLC (clinicaltrials.gov) - P3 | N=791 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2030 ➔ Sep 2027 | Trial primary completion date: Jul 2028 ➔ Aug 2026

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

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 with domvanalimab + zimberelimab combination in patients with advanced rare cancers—The B3 Thymomas and Thymic Carcinomas Cohort. (ASCO 2025) - P2 | "Translational research projects will be developed aiming at deciphering cellular and molecular mechanisms involved in response to treatment. Moreover, data from the prospective database of the RYTHMIC network will be investigated to build a synthetic historical arm representative of the efficacy of the standard treatments in a similar population of patients."

Clinical • Metastases • P2 data • Oncology • Solid Tumor • Thoracic Cancer • Thymic Carcinoma • Thymoma • Thymus Cancer • TIGIT

AB122 Platform Study (clinicaltrials.gov) - P1 | N=917 | Recruiting | Sponsor: Taiho Pharmaceutical Co., Ltd. | Trial completion date: May 2026 ➔ Jun 2027 | Trial primary completion date: May 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • Alveolar Soft Tissue Sarcoma • Biliary Cancer • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Head and Neck Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Domvanalimab plus zimberelimab in unresectable and immunotherapy refractory biliary tract cancers: a phase 2 trial. (PubMed, Nat Commun) - P2 | "Emergent circulating tumor DNA alterations in RAS signaling, receptor tyrosine kinases, and DNA damage response were identified as putative mechanisms of anti-TIGIT resistance. Although the prespecified ORR threshold was not met, the durability of responses, favorable safety profile, and translational findings support further evaluation of anti-TIGIT-based combination strategies in BTCs."

Journal • P2 data • Biliary Cancer • Biliary Tract Cancer • Dermatology • Oncology • Pruritus • Solid Tumor • TIGIT

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 With Domvanalimab + Zimberelimab Combination in Patients With Advanced RARE Cancers (clinicaltrials.gov) - P2 | N=27 | Active, not recruiting | Sponsor: Hospices Civils de Lyon | Recruiting ➔ Active, not recruiting | N=154 ➔ 27

Enrollment change • Enrollment closed • Carcinoid Tumor • Endocrine Cancer • Gastrointestinal Neuroendocrine Tumor • Gestational Trophoblastic Neoplasia • Mesothelioma • Neuroendocrine Tumor • Oncology • Peritoneal Mesothelioma • Solid Tumor • Thymic Carcinoma • Thymus Cancer • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma

STU-2022-1076: Domvanalimab and Zimberelimab in Advanced Liver Cancers (clinicaltrials.gov) - P2 | N=58 | Active, not recruiting | Sponsor: University of Texas Southwestern Medical Center | Trial completion date: Jun 2028 ➔ Dec 2029 | Trial primary completion date: Jul 2027 ➔ Dec 2027

Pan tumor • Trial completion date • Trial primary completion date • Biliary Cancer • Cholangiocarcinoma • Gallbladder Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

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 | Terminated | Sponsor: Arcus Biosciences, Inc. | Active, not recruiting ➔ Terminated

Trial termination • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor

STAR-221 at ESMO GI 2026: Domvanalimab Plus Zimberelimab in HER2-Negative Advanced Gastric Cancer (OncoDaily) - "The study did not meet its primary endpoint of overall survival. After a median follow-up of approximately 13 months, median OS was 14.0 months with domvanalimab + zimberelimab + chemotherapy compared with 13.4 months with nivolumab + chemotherapy (HR 1.01; P = 0.526), demonstrating no significant survival advantage in the intention-to-treat population....Progression-free survival was nearly identical between the two treatment arms. Median PFS was 8.4 months with domvanalimab + zimberelimab + chemotherapy and 8.3 months with nivolumab + chemotherapy, with no progression-free survival advantage observed in either the overall study population or the predefined biomarker subgroups....Objective response rates were also comparable between treatment groups. The ORR was 55% with domvanalimab + zimberelimab + chemotherapy and 56% with nivolumab + chemotherapy."

P3 data • Esophageal Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma

ARC-7: Study to Evaluate Monotherapy and Combination Immunotherapies in Participants With PD-L1 Positive Non-small Cell Lung Cancer (clinicaltrials.gov) - P2; N=150; Recruiting; Sponsor: Arcus Biosciences, Inc.; Initiation date: Jan 2020 ➔ May 2020

Clinical • Combination therapy • Monotherapy • Trial initiation date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • ALK • EGFR • PD-L1

A Global Study to Assess the Effects of Durvalumab + Domvanalimab Following Concurrent Chemoradiation in Participants With Stage III Unresectable NSCLC (PACIFIC-8) (clinicaltrials.gov) - P3 | N=860 | Not yet recruiting | Sponsor: AstraZeneca

New P3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • PD-L1

ARC-7: Study to Evaluate Monotherapy and Combination Immunotherapies in Participants With PD-L1 Positive Non-small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: Arcus Biosciences, Inc. | Trial completion date: Jun 2022 ➔ Feb 2023 | Trial primary completion date: Mar 2022 ➔ Nov 2022

Combination therapy • Monotherapy • 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

ARC-7: Study to Evaluate Monotherapy and Combination Immunotherapies in Participants With PD-L1 Positive Non-small Cell Lung Cancer (clinicaltrials.gov) - P2; N=150; Recruiting; Sponsor: Arcus Biosciences, Inc.

Clinical • Combination therapy • Monotherapy • New P2 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Thoracic Cancer • ALK • EGFR • PD-L1

STU-2022-1076: Domvanalimab and Zimberelimab in Advanced Liver Cancers (clinicaltrials.gov) - P2 | N=58 | Active, not recruiting | Sponsor: University of Texas Southwestern Medical Center | Trial completion date: Jun 2027 ➔ Jun 2028 | Trial primary completion date: Jul 2026 ➔ Jul 2027

Pan tumor • Trial completion date • Trial primary completion date • Biliary Cancer • Cholangiocarcinoma • Gallbladder Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor