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

VELOCITY-Lung: Study of Novel Treatment Combinations in Patients With Lung Cancer (clinicaltrials.gov) - P2 | N=270 | Recruiting | Sponsor: Gilead Sciences | N=593 ➔ 270

Enrollment change • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-L1

PRODIGE 113 (FFCD 2314) – REWENEC – 01 STUDY Randomized trial of FOLFIRI + Zimberelimab + Domvanalimab vs FOLFIRI with a hybrid synthetic control arm in second line treatment of metastatic neuroendocrine carcinoma of gastro-enteropancreatic or unknown origin. Phase II comparative randomized study – multicentric (clinicaltrialsregister.eu) - P1/2 | N=77 | Sponsor: Hospices Civils De Lyon

New P1/2 trial • Gastrointestinal Neuroendocrine Carcinoma • Neuroendocrine Carcinoma • Oncology • Pancreatic Cancer • Solid Tumor

PeRioperative Immunotherapy Combined With Sacituzumab Govitecan in Muscle Invasive blAdder Cancer (clinicaltrials.gov) - P2 | N=70 | Active, not recruiting | Sponsor: Fundación para el Progreso de la Oncología en Cantabria | Recruiting ➔ Active, not recruiting | Trial primary completion date: Dec 2030 ➔ Jan 2030

Enrollment closed • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Domvanalimab combined with zimberelimab as first-line treatment in patients with PD-L1-high, advanced non-small cell lung cancer: Results from the randomized phase 2 ARC-10 study, Part1. (PubMed, Lung Cancer) - "Adding Fc-silent anti-TIGIT (domvanalimab) to anti-PD-1 (zimberelimab) led to encouraging efficacy and showed no new safety concerns in patients with previously untreated stage IIIB-IV NSCLC."

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

PRODIGE 111 DOMZIGASTnA randomized phase II study evaluating FOLFIRI vs FOLFIRI plus Domvanalimab (anti-TIGIT) and Zimberelimab (anti-PD1) in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma with progression during or after peri-operative chemotherapy. (clinicaltrialsregister.eu) - P1/2 | N=95 | Completed | Sponsor: Fondation Franc.Cancerologie Digestive | Not yet recruiting ➔ Completed

Trial completion • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2 • PD-L1

PRODIGE 111 DOMZIGASTnA randomized phase II study evaluating FOLFIRI vs FOLFIRI plus Domvanalimab (anti-TIGIT) and Zimberelimab (anti-PD1) in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma with progression during or after peri-operative chemotherapy. (clinicaltrialsregister.eu) - P1/2 | N=95 | Not yet recruiting | Sponsor: Fondation Franc.Cancerologie Digestive

New P1/2 trial • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2 • PD-L1

MEDOPP0653: A PHASE II TRIAL EVALUATING THE SAFETY AND EFFICACY OF THE COMBINATION OF ZIMBERELIMAB, DOMVANALIMAB, AND SACITUZUMAB GOVITECAN AS FIRST-LINE THERAPY FOR PD-L1 POSITIVE ADVANCED TRIPLE-NEGATIVE BREAST CANCER (The ADJUNCT Study) (clinicaltrialsregister.eu) - P1/2 | N=25 | Not yet recruiting | Sponsor: Medica Scientia Innovation Research S.L.

New P1/2 trial • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

Switch Maintenance in Pancreatic (clinicaltrials.gov) - P1/2 | N=46 | Suspended | Sponsor: James Cleary, MD, PhD | Trial primary completion date: Jan 2026 ➔ Jan 2027

Trial primary completion date • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma

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=100 | Active, not recruiting | Sponsor: Gilead Sciences | Recruiting ➔ Active, not recruiting

Enrollment closed • IO biomarker • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Domvanalimab combined with zimberelimab as first-line treatment in patients with PD-L1–high, advanced non-small cell lung cancer: Results from the randomized phase 2 ARC-10 study, Part1 (Lung Cancer) - "Median (95% CI) OS was not reached (13.7-not evaluable [NE]) for DZ, 24.4(7.8-NE) months for Z, and 11.9(2.7-NE) months for chemotherapy. DZ vs Z hazard ratio (95% CI) was 0.69 (0.40–1.18) for PFS and 0.64 (0.32–1.25) for OS. ORR (95% CI) was 44.7% (28.6–61.7) for DZ, 35.0% (20.6–51.7) for Z, and 35.3% (14.2–61.7) for chemotherapy."

P2 data • Non Small Cell Lung Cancer

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

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

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

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

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