Zimberelimab

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Also known as:

WBP-3055 GLS-010 AB122

Cancer types include:

brain tumor breast cancer cervical cancer head and neck cancer kidney cancer

TrialFetch AI Analysis

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Overview

Zimberelimab (also known as AB122, GLS-010, WBP-3055) is a fully human IgG4 monoclonal antibody targeting PD-1, developed using the OmniRat transgenic platform. It has been evaluated as monotherapy and in combinations across multiple solid tumors and hematologic malignancies. In China, zimberelimab is approved for relapsed/refractory classical Hodgkin lymphoma (r/r cHL; 2021) and for PD-L1–positive recurrent/metastatic cervical cancer (2023); development continues globally where it remains investigational. (pubmed.ncbi.nlm.nih.gov)

Mechanism of action

Zimberelimab binds PD-1 with high affinity (KD ≈ 1.75×10⁻¹⁰ M), blocking PD‑L1/PD‑L2 interactions and restoring T‑cell activity. Preclinical studies demonstrated effective checkpoint blockade and antitumor activity in PD‑1 humanized mouse models. (pubmed.ncbi.nlm.nih.gov)

Efficacy

Classical Hodgkin lymphoma (r/r cHL; phase II, single arm, n=85): Objective response rate (ORR) 90.6% (95% CI 82.3–95.9); complete response (CR) 32.9%. Twelve‑month PFS and OS were 78% and 99%, respectively. (pubmed.ncbi.nlm.nih.gov)
Cervical cancer (recurrent/metastatic, PD‑L1–positive; phase II, single arm, n=105): ORR 27.6%; disease control rate 55.2%; median PFS 3.7 months; median OS 16.8 months; duration of response not reached at 16.9‑month median follow‑up. Results supported approval in China. (pubmed.ncbi.nlm.nih.gov)
Gastric cancer (AFP‑elevated; phase I, combination with lenvatinib + XELOX; n=9): ORR 33.3%; all patients achieved disease control; median PFS 7.67 months and OS 13.17 months in a small dose‑escalation cohort. (pmc.ncbi.nlm.nih.gov)
Esophageal cancer (first‑line; phase 1a/b, zimberelimab + futibatinib + FP chemotherapy; ASCO 2025 abstract): Confirmed ORR 58.5% (overall ORR 70.7%); disease control rate 92.7%; median PFS 4.9 months; data are preliminary. (ascopubs.org)
Non–small cell lung cancer (NSCLC; PD‑L1‑high): In randomized studies, adding domvanalimab (anti‑TIGIT) to zimberelimab improved outcomes versus zimberelimab alone (e.g., PFS improvement in ARC‑7; OS improvement in ARC‑10 Part 1), though detailed peer‑reviewed data are pending. A phase 3 ARC‑10 design comparing domvanalimab+zimberelimab to pembrolizumab has been described. (investors.gilead.com)

Safety

Across studies, zimberelimab’s safety profile is consistent with PD‑1 inhibitors. In r/r cHL, treatment‑related adverse events (TRAEs) occurred in 92.9%; grade ≥3 TRAEs in 28.2% (most common: hepatic lab abnormalities, hyperuricemia, neutropenia); one grade 5 AE (GI infection). (pubmed.ncbi.nlm.nih.gov)
In PD‑L1–positive recurrent/metastatic cervical cancer, any‑grade TRAEs occurred in 78.1% (most common: hypothyroidism 26.7%, anemia 19.0%); grade ≥3 TRAEs in 22.9% in a related analysis. (pubmed.ncbi.nlm.nih.gov)
In combinations, early‑phase studies reported manageable safety without new signals (e.g., lenvatinib+chemotherapy in AFP‑elevated gastric cancer; futibatinib+chemotherapy in esophageal cancer). (pmc.ncbi.nlm.nih.gov)

Regulatory status and development notes

China approvals: r/r cHL (August 2021) and PD‑L1–positive recurrent/metastatic cervical cancer (September 2023). Outside China, zimberelimab is investigational. (gilead.com)
Partnerships: The antibody (GLS‑010) originated with Gloria Biosciences/WuXi Biologics and was licensed to Arcus Biosciences for development ex‑China. Ongoing programs include combinations with domvanalimab (anti‑TIGIT) and etrumadenant (A2a/A2b antagonist). (wuxibiologics.com)

Active trials using Zimberelimab

Found 5 active trials using this drug:

A Phase 2 Platform Study of Novel Combination Therapies in Participants With Head and Neck Squamous Cell Carcinoma

Sponsor: Gilead Sciences (industry) Phase: 2 Start date: Feb. 18, 2025

TrialFetch AI summary: First-line study for adults with recurrent/metastatic, non-nasopharyngeal HNSCC (ECOG 0–1, measurable disease, no prior PD-1/TIGIT; prior curative-intent platinum allowed if relapse >6 months) comparing zimberelimab (anti–PD-1) plus carboplatin/paclitaxel with or without domvanalimab, an Fc-silent anti-TIGIT antibody that augments T-cell activity. Aims to determine whether adding anti-TIGIT to PD-1 blockade and platinum-taxane chemotherapy improves ORR and PFS.

ClinicalTrials.gov ID: NCT06727565

Phase I/II Study of Stereotactic Radiation and Sacituzumab Govitecan With Zimberelimab in the Management of Metastatic Triple Negative Breast Cancer With Brain Metastases (TARGET-TNBC)

Sponsor: H. Lee Moffitt Cancer Center and Research Institute (other) Phase: 1/2 Start date: Dec. 19, 2024

TrialFetch AI summary: Eligible patients are adults with metastatic triple-negative breast cancer and measurable brain metastases who can undergo stereotactic radiosurgery; treatment consists of SRS followed by sacituzumab govitecan (an anti-Trop-2 antibody-drug conjugate) and zimberelimab (a PD-1 inhibitor immunotherapy). Prior taxane/anthracycline or SRS/FSRT therapy (if new lesions) is allowed; key exclusions are leptomeningeal disease, significant comorbidities, active autoimmune disease requiring immunosuppression, and prior topoisomerase I inhibitor use for brain metastases.

ClinicalTrials.gov ID: NCT06238921

Phase II Single Arm Study Testing SBRT, Adenosine Signaling Modulation (AB680, AB928), and Immune Checkpoint Inhibition (AB122) for Men With Hormone Sensitive Oligometastatic Prostate Cancer

Sponsor: Catherine Spina (other) Phase: 2 Start date: July 1, 2023

TrialFetch AI summary: Men with hormone-sensitive oligometastatic prostate adenocarcinoma (1–3 SBRT-amenable lesions; prior definitive therapy; testosterone >125 ng/dL; PSA 0.5–50; PSADT <15 months; ECOG 0–2) receive metastasis-directed SBRT plus adenosine-axis modulation with quemliclustat (CD73 inhibitor) and etrumadenant (A2A/A2B receptor antagonist) followed by PD-1 blockade with zimberelimab. Aims to improve biochemical and radiographic control versus historical SBRT alone while deferring ADT.

ClinicalTrials.gov ID: NCT05915442

A Phase 1, Open-label, Dose Escalation and Dose Expansion Study, to Investigate the Safety, Tolerability, and Pharmacokinetic Profile of AB521 Monotherapy and Combination Therapies in Participants With Clear Cell Renal Cell Carcinoma and Other Solid Tumors

Sponsor: Arcus Biosciences, Inc. (industry) Phase: 1 Start date: Oct. 26, 2022

TrialFetch AI summary: Adults with ECOG 0–1: dose escalation enrolls any advanced solid tumor lacking standard options; expansion enrolls histologically confirmed ccRCC. Treatments include the oral HIF-2α inhibitor casdatifan (AB521) as monotherapy or combined with cabozantinib or the anti–PD-1 antibody zimberelimab.

ClinicalTrials.gov ID: NCT05536141

Phase II Study of PD-1 Inhibitor Zimberelimab (AB122) With TIGIT Inhibitor Domvanalimab (AB154) in PD-1 Relapsed/Refractory Melanoma

Sponsor: Diwakar Davar (other) Phase: 2 Start date: March 16, 2022

TrialFetch AI summary: Adults with cutaneous melanoma (non-mucosal/ocular/acral) that has progressed on prior anti–PD-1/L1 therapy receive zimberelimab (anti–PD-1) plus domvanalimab (Fc-silent anti-TIGIT) every 3 weeks, with continuation for disease control up to 24 months. Prior CTLA-4 and, if BRAF-mutant, BRAF/MEK therapy allowed; requires ECOG 0–1, excludes active autoimmune disease, prior TIGIT therapy, and uncontrolled/active CNS disease (treated, stable brain mets allowed).

ClinicalTrials.gov ID: NCT05130177