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

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

Domvanalimab (Fc-silent anti-TIGIT antibody) plus Zimberelimab (anti-PD-1 antibody):…Planned Data Readout (Businesswire) - "Data from the ongoing Phase 3 study STAR-221, evaluating domvanalimab plus zimberelimab and chemotherapy in PD-L1 all-comer 1L unresectable or metastatic upper GI adenocarcinomas are expected in 2026."

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

TIGIT, CD155 (PVR), and Trop-2 expression characterization across histology and PD-L1 subgroups in non−small cell lung cancer (NSCLC) (AACR-NCI-EORTC 2025) - P2, P3 | "Novel combinations of domvanalimab (dom, anti-TIGIT) ± sacituzumab govitecan (SG, Trop-2−directed ADC) ± zimberelimab (zim, anti-PD-1) ± standard of care are being studied in NSCLC in the VELOCITY-Lung (NCT05633667), EDGE-Lung (NCT05676931), STAR-121 (NCT05502237), EVOKE-02 (NCT05186974), and EVOKE-03 (NCT05609968) clinical trials. TIGIT was expressed across histology and PD-L1 subgroups, including PD-L1 negative, suggesting dom/zim as a potential treatment combination across NSCLC subtypes and PD-L1 subgroups. Consistent with published data, CD155 and TIGIT expression were significantly higher in PD-L1-high and sq samples. These biomarkers' predictive/prognostic values will be evaluated in the context of efficacy in clinical studies testing combinations of dom/zim and SG in NSCLC."

IO biomarker • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • PD-L1 • PVR • TACSTD2 • TIGIT

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

Domvanalimab and zimberelimab in advanced gastric, gastroesophageal junction or esophageal cancer: a phase 2 trial. (PubMed, Nat Med) - P2 | "In arm A1, presented here, dual blockade of TIGIT and PD-1 with domvanalimab (Fc-silent anti-TIGIT) and zimberelimab (anti-PD-1) plus oxaliplatin, leucovorin, fluorouracil (FOLFOX) was evaluated in patients with previously untreated advanced HER2-negative gastric, gastroesophageal junction or esophageal adenocarcinoma. Dual TIGIT and PD-1 blockade with domvanalimab and zimberelimab plus chemotherapy demonstrated encouraging efficacy, and the regimen is being evaluated in the phase 3 STAR-221 trial. ClinicalTrials.gov identifier: NCT05329766 ."

Journal • P2 data • 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=593 | Recruiting | Sponsor: Gilead Sciences | Trial completion date: Dec 2028 ➔ Sep 2029 | Trial primary completion date: Jan 2027 ➔ Sep 2029

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

Gilead and Kite Reinforce Bold Commitment to Transform Cancer Care With New Data at ESMO 2025 (Businesswire)

Clinical data • Diffuse Large B Cell Lymphoma • Non Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck

Anti-TIGIT Domvanalimab Plus Anti-PD-1 Zimberelimab and Chemotherapy Showed 26.7 Months of Median Overall Survival as First-Line Treatment of Unresectable or Advanced Gastroesophageal Adenocarcinomas in the Phase 2 EDGE-Gastric Study (Businesswire) - "These results will be presented in a mini oral session at the ESMO 2025 Congress (Presentation Number 2112MO)....Efficacy was observed across all PD-L1 subgroups. With a median time on treatment of 49 weeks (range: <1-117 weeks), the domvanalimab plus zimberelimab and chemotherapy regimen demonstrated sustained efficacy with longer follow-up."

P2 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma

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=154 | Recruiting | Sponsor: Hospices Civils de Lyon | Initiation date: May 2025 ➔ Oct 2025 | Not yet recruiting ➔ Recruiting

Enrollment open • Trial initiation date • Carcinoid Tumor • Endocrine Cancer • Gestational Trophoblastic Neoplasia • Mesothelioma • Neuroendocrine Tumor • Oncology • Peritoneal Mesothelioma • Solid Tumor • Thymic Carcinoma • Thymoma • Thymus Cancer • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma

EDGE-Lung: Study With Various Immunotherapy Treatments in Participants With Lung Cancer (clinicaltrials.gov) - P2 | N=400 | Active, not recruiting | Sponsor: Gilead Sciences | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

ADJUNCT: Phase II Trial Evaluating the Safety and Efficacy of the Combination of Zimberelimab, Domvanalimab and Sacituzumab Govitecan as 1L Therapy for PD-L1 Positive Advanced TNBC (clinicaltrials.gov) - P2 | N=25 | Not yet recruiting | Sponsor: MedSIR

New P2 trial • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

ARC-7: Study to Evaluate Monotherapy and Combination Immunotherapies in Participants With PD-L1 Positive Non-small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=151 | Completed | Sponsor: Arcus Biosciences, Inc. | Active, not recruiting ➔ Completed

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

AB154 Combined With AB122 for Recurrent Glioblastoma (clinicaltrials.gov) - P1 | N=46 | Recruiting | Sponsor: Yale University | Active, not recruiting ➔ Recruiting

Enrollment open • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

VELOCITY-Lung: Study of Novel Treatment Combinations in Patients With Lung Cancer (clinicaltrials.gov) - P2 | N=593 | Recruiting | Sponsor: Gilead Sciences | Trial completion date: Jan 2027 ➔ Dec 2028

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

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 primary completion date: Jul 2025 ➔ Oct 2025 | Trial completion date: Sep 2029 ➔ Dec 2029

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

Arcus Biosciences Reports Second-Quarter 2025 Financial Results and Provides a Pipeline Update (Businesswire) - "Pipeline Highlights:... Domvanalimab (Fc-silent anti-TIGIT antibody) plus Zimberelimab (anti-PD-1 antibody): Planned Data Readouts: (i) An abstract describing OS data from the Phase 2 EDGE-Gastric study, evaluating domvanalimab plus zimberelimab and chemotherapy in upper GI adenocarcinomas, has been accepted for presentation at the 2025 ESMO Congress in October; (ii) The first Phase 3 OS data readout for domvanalimab plus zimberelimab will be from the ongoing Phase 3 study STAR-221, evaluating domvanalimab plus zimberelimab plus chemotherapy in PD-L1 all-comer 1L unresectable or metastatic upper GI adenocarcinomas. Results for this trial are event-driven, and OS data are expected in 2026."

P2 data • P3 data • Esophageal Adenocarcinoma • Gastric Adenocarcinoma • Gastroesophageal Junction Adenocarcinoma

Imfinzi + domvanalimab: Data from P3 PACIFIC-8 trial (NCT05211895) for stage 3 NSCLC post 2026 (AstraZeneca) - H1 and Q2 2025 Results

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

Zimberelimab + domvanalimab: Completion of P3 STAR-121 trial (NCT05502237) for stage IV NSCLC in Jun 2028 (Otsuka) - Q2 FY2025 Results

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology