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

The Randomized Phase 2 ARC-9 Study of Etrumadenant-Based Therapy vs Regorafenib in Patients with Previously Treated Metastatic Colorectal Cancer. (PubMed, Clin Cancer Res) - P1/2 | "EZFB significantly improved survival outcomes compared with regorafenib in patients with mCRC as a third-line treatment, with a manageable safety profile. Further investigation is warranted, given the clinically meaningful improvements in progression-free survival and overall survival."

Journal • P2 data • Colorectal Cancer • Oncology • Solid Tumor

Pre-NEOSHIFT-RCC: Neoadjuvant HIF-Inhibitor Immunotherapy in RCC (clinicaltrials.gov) - P2 | N=32 | Recruiting | Sponsor: Dana-Farber Cancer Institute | Not yet recruiting ➔ Recruiting | Initiation date: Jul 2026 ➔ Mar 2026

Enrollment open • Trial initiation date • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

A Single-arm, Multicenter Clinical Study of Becotatug Vedotin Combined With Zimberelimab in the Treatment of Recurrent and Metastatic Cervical Cancer, Vulvar Cancer and Vaginal Cancer (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

New P2 trial • Cervical Cancer • Gynecologic Cancers • Oncology • Solid Tumor • Vaginal Cancer • Vulvar Cancer

Phase II study of magrolimab combination therapies in patients with head and neck squamous-cell carcinoma. (PubMed, ESMO Open) - "There was no benefit observed with magrolimab treatment. The study closed prematurely, limiting interpretation."

Journal • P2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

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

Zimberelimab Plus Lenvatinib After Progression on Prior Immune Checkpoint Inhibitors for Advanced Cervical Cancer (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: Sun Yat-sen University | Not yet recruiting ➔ Active, not recruiting

Checkpoint inhibition • Enrollment closed • Cervical Cancer • Oncology • Solid Tumor

A Phase 2 Study to Evaluate the Triplet Combination of Pemetrexed Plus AB928 (Etrumadenant) + AB122 (Zimberelimab) in Patients With Previously Treated Advanced or Metastatic MTAP Deficient Urothelial Carcinoma (clinicaltrials.gov) - P2 | N=10 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Active, not recruiting | N=20 ➔ 10

Enrollment change • Enrollment closed • Oncology • Solid Tumor • Urothelial Cancer • IL17A • MTAP

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

Bladder Preservation with Sacituzumab Govitecan + Zimberelimab for MuscleInvasive Bladder cancer in cisplatin-unfit and unwilling for cystectomy patients: phase II trial (preSAVE trial) (clinicaltrialsregister.eu) - P1/2 | N=62 | Not yet recruiting | Sponsor: Fondazione IRCCS Istituto Nazionale Dei Tumori

New P1/2 trial • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • CD4

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

The clinical benefit from treatment of advanced MSS mCRC with the adenosine 2a/2b antagonist etrumadenant is associated with adenosine-mediated T-cell exclusion and enhancement of the effectiveness of immunotherapy (AACR-IO 2026) - P1/2 | "Etruma, in combination with zimberelimab (Z) (an anti-PD-1 antibody) and FOLFOX/bevacizumab (bev) (EZFB regimen) demonstrated a significant overall survival (OS) benefit over regorafenib (rego) in third-line, MSS, chemo-resistant mCRC in the ARC-9 Ph2 study (NCT04660812)... The majority of ARC-9 patients were shown to have CD73+, T cell excluded tumors and experienced robust clinical benefit on EZFB regardless of CD73 or PD-L1 status. Patients with CD73+ PD-L1high tumors derived the greatest benefit, supporting the hypothesis that clinical efficacy on this regimen is fundamentally underpinned by reversal of T cell exclusion and reinvigoration of T cell mediated anti-tumor immunity in the late-line, MSS chemo-resistant mCRC. Citation Format: Jiyun Kim, Emily Brown, Shravani Shitole, Madhura Joglekar, Haben Ghermazien, Jose Aquino, Tingting Zhao, Jennifer Scott, Soonweng Cho, Angelo Kaplan, Omar Kabbarah."

Clinical • IO biomarker • Metastases • Colorectal Cancer • Solid Tumor • CD73 • CD8 • GZMB • NT5E • 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

ARC-20: A Phase 1 Study of AB521 Monotherapy and Combination Therapies in Renal Cell Carcinoma and Other Solid Tumors (clinicaltrials.gov) - P1 | N=362 | Recruiting | Sponsor: Arcus Biosciences, Inc. | Trial completion date: Jul 2027 ➔ Mar 2029 | Trial primary completion date: Jul 2027 ➔ Mar 2029

Monotherapy • Trial completion date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

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

AIO-TRK/YMO-0224: 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 (NeoTRACE) (clinicaltrialsregister.eu) - P1/2 | N=50 | Not yet recruiting | Sponsor: AIO-Studien gGmbH

New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

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

Zimberelimab plus lenvatinib in patients with advanced cervical cancer who progressed after prior immune checkpoint inhibitors: a multicenter, single-arm, phase II trial (SGO 2025) - No abstract available

Checkpoint inhibition • Clinical • Metastases • P2 data • Cervical 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 (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

ARC-9: A randomized study to evaluate etrumadenant based treatment combinations in previously treated metastatic colorectal cancer (mCRC). (ASCO 2024) - P1/2 | "ARC-9 (NCT04660812), a Phase Ib/II trial evaluating the safety and efficacy of E combined with zimberelimab (Z) (anti-PD-1 antibody), and FOLFOX/bevacizumab (bev) regimens or novel therapies in 3 cohorts of patients (pts) with mCRC... Cohort B enrolled pts who previously progressed on both oxaliplatin and irinotecan containing regimens.Pts were randomized 2:1 to EZFB: E (150 mg orally [PO] once daily [QD]) + Z (240 mg intravenous [IV] once every 2 weeks [Q2W]) + mFOLFOX-6 + bev (5 mg/kg IV Q2W), or regorafenib (rego) (160 mg PO QD [days 1-21 every 4 weeks])... In this randomized phase II clinical trial, EZFBsignificantlyimproved efficacy outcomes compared to rego in refractory mCRC pts previously treated with 5-FU, oxaliplatin and irinotecan regimens with no unexpected toxicities. Further investigation of this promising regimen is warranted given the clinically meaningful PFS and OS improvement. Table"

Clinical • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

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