Yutuo (zimberelimab) / Gloria Pharma, WuXi AppTec, Arcus Biosci, Ligand, Otsuka, Gilead - LARVOL DELTA

Iparomlimab and tuvonralimab (QL1706) vs zimberelimab for previously treated recurrent/metastatic cervical cancer (r/mCC): An unanchored matching-adjusted indirect comparison (MAIC) (ESMO Asia 2025) - P2 | "For efficacy and safety analysis, adjustments were made for age, histologic type, Eastern Cooperative Oncology Group (ECOG) performance status (PS), combined positive score (CPS), prior treatment lines, prior bevacizumab use and prior radiotherapy. After matching, QL1706 had effective sample sizes (ESS) of 90 for efficacy and 90.2 for safety analyses. These findings indicate that QL1706 demonstrated favourable efficacy and a comparable safety profile compared to zimberelimab for previously treated r/mCC patients. QL1706 could potentially serve as a new standard treatment option for this population."

Metastases • Cervical Cancer • Oncology • Solid Tumor • PD-L1

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

Successful sequential chemo-immunotherapy and reduced-volume brachytherapy for bulky residual cervical tumor after external beam radiotherapy: two case reports. (PubMed, Front Immunol) - "After sequential treatment with albumin-bound paclitaxel plus cisplatin combined with zimberelimab, both patients achieved marked tumor volume reduction and subsequently underwent reduced-volume BT. Sequential chemo-immunotherapy followed by reduced-volume BT may represent an alternative treatment option for patients with bulky residual disease after EBRT. Further clinical studies are warranted to validate the effectiveness of this combined regimen."

Journal • Cervical Cancer • Cervical Squamous Cell Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma

Phase I Study of Stereotactic Radiation and Sacituzumab Govitecan with Zimberelimab in the Management of Metastatic Triple Negative Breast Cancer with Brain Metastases (SABCS 2025) - P1, P1/2, P3 | "Results from the phase I portion reveals safety of a combined approach. Efficacy continues to be assessed in the phase II portion."

Metastases • P1 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Study design and rationale for the NeoTRACE trial: a multicenter phase II study of neoadjuvant sacituzumab govitecan plus zimberelimab followed by adjuvant zimberelimab with or without sacituzumab govitecan in patients with resectable non-small cell lung cancer. (PubMed, Future Oncol) - "Previous studies showed ADC and immunotherapy combinations are effective in advanced NSCLC, suggesting potential perioperative benefit. This study aims to improve pCR rate, reduce toxicity, enhance surgical eligibility, and personalize adjuvant treatment to improve long-term outcomes.Clinical Trial Registration: EudraCT: 2024-517561-16."

IO biomarker • Journal • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • TACSTD2

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 First in human clinical trial to assess the anti-IL18BP antibody, COM503(GS-0321) in Participants with Advanced Solid Malignancies (SITC 2025) - P1 | "Background Conventional cytokines have limited anti-cancer efficacy mostly due to narrow therapeutic window and systemic adverse effects.1 IL-18 is an inflammasome induced proinflammatory cytokine that activates T and NK cells and stimulates IFNg production.2 3 The activity of IL-18 is naturally blocked by a high affinity endogenous binding protein (IL-18BP),2 which is induced in response to IFNg upregulation as a negative feedback mechanism.4 An anti-mouse IL-18BP Ab induces potent anti-tumor responses either alone or in combination with anti-PD-L1 Ab coupled with pronounced TME-constrained immune modulation.5 This is in contrast to systemically administered therapeutic cytokines, which generate a non-localized inflammatory response.6 COM503 (also known as GS-0321), a high-affinity anti-IL -18BP Ab, as monotherapy as well as in combination with anti-PD-1 antibodies has been shown to induce human T and NK cell responses in vitro5 and is currently undergoing clinical..."

Clinical • First-in-human • Metastases • P1 data • Oncology • Solid Tumor • IFNG • IL18 • IL18BP

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

Tumor Biomarker Analysis of Anti-CD39 Monoclonal Antibody AB598 in a First-In-Human Phase I Trial in Patients with Advanced Solid Tumors (SITC 2025) - P1 | "ARC-25 (NCT05891171) is a phase 1/1b trial to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AB598 monotherapy and combination therapy with zimberelimab (anti-PD-1) and standard-of-care chemotherapy. Enrollment at any clinical study site did not begin prior to that site receiving approval from the ethics committee of record for the protocol and all materials provided to potential patients. All participants provided informed consent prior to any clinical research sample collection."

Biomarker • Clinical • First-in-human • IO biomarker • Metastases • P1 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • ENTPD1

Peripheral pharmacodynamic analysis of anti-CD39 monoclonal antibody AB598 in a first-in-human phase I trial in patients with advanced solid tumors (SITC 2025) - P1 | "ARC-25 (NCT05891171) is an ongoing phase 1/1b first-in-human trial to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity of both AB598 monotherapy and AB598 in combination with zimberelimab (anti-PD1) and mFOLFOX chemotherapy in patients with advanced solid tumors.Methods Here we present peripheral PD data from AB598 monotherapy dose escalation cohorts (31 subjects dosed at 300, 900, 1800, or 3000 mg Q3W). Enrollment at any clinical study site did not begin prior to that site receiving approval from the ethics committee of record for the protocol and all materials provided to potential patients. All participants provided informed consent prior to any clinical research sample collection."

Clinical • First-in-human • IO biomarker • Metastases • P1 data • PK/PD data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • ENTPD1

ARC-9: An Open Label Study Evaluating the Efficacy and Safety of Etrumadenant (AB928) Based Treatment Combinations in Participants With Metastatic Colorectal Cancer. (clinicaltrials.gov) - P1/2 | N=227 | Completed | Sponsor: Arcus Biosciences, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Mar 2026 ➔ Sep 2025

Trial completion • Trial completion date • Colorectal 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 | 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

Clinical pharmacokinetic/pharmacodynamic relationship for AB598, a large molecule inhibitor of CD39 (AACR-NCI-EORTC 2025) - P1 | "AB598 is under investigation in a first-in-human, multicenter, non-randomized, open-label phase 1 study in patients with advanced solid tumors (NCT05891171).Objective· To characterize the pharmacokinetics (PK) of AB598 in cancer patients · To describe the relationship between AB598 PK and tumor pharmacodynamic (PD) markers (receptor occupancy and enzymatic inhibition) to inform the selection of an appropriate dose for future clinical trials.Methods· The study consists of two phases: a monotherapy AB598 dose escalation phase (300 mg, 900 mg, 1800 mg and 3000 mg IV Q3W) that is complete, and an ongoing combination dose expansion phase (AB598 + FOLFOX + zimberelimab)...· AB598 half-life is consistent with other anti-CD39 antibodies. · 2000 mg IV Q2W observed concentrations adequately achieve the target effective concentrations."

Clinical • PK/PD data • Oncology • Solid Tumor • ENTPD1

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