A Phase 1/1b Study to Evaluate the Safety and Tolerability of AB598 Monotherapy and Combination Therapy in Participants With Advanced Malignancies

Overview

Zimberelimab, also known as WBP-3055, GLS-010, or AB122, is a fully human anti-PD-1 monoclonal antibody developed for the treatment of various cancers. It has been evaluated in multiple clinical trials, demonstrating efficacy and safety across different malignancies.

Mechanism of Action

Zimberelimab targets the programmed death-1 (PD-1) receptor, a checkpoint protein on T cells that, when engaged by its ligands, inhibits T-cell activation. By blocking PD-1, zimberelimab enhances the immune system's ability to detect and destroy cancer cells.

Efficacy

Relapsed or Refractory Classical Hodgkin Lymphoma (R/R cHL):

In the Phase II YH-S001-04 trial, 75 patients with R/R cHL received zimberelimab 240 mg every two weeks. With a median follow-up of 38 months, the objective response rate (ORR) was 91.6% (95% CI, 83.8-95.9). The median progression-free survival (PFS) was 23.6 months, and the 3-year overall survival (OS) rate was 94.0% (95% CI, 85.9-97.4). (pubmed.ncbi.nlm.nih.gov)

Recurrent or Metastatic Cervical Cancer (R/M CC):

A pivotal Phase II study (YH-S001-05) evaluated zimberelimab monotherapy in 90 patients with R/M CC. The ORR was 27.8%, with 5.6% achieving complete remission and 22.2% partial remission. The median PFS was 3.7 months, and the median OS was 16.8 months. (pipelinereview.com)

Advanced Cervical Cancer Post-ICI Therapy:

In a Phase II trial, 30 patients with advanced cervical cancer who had progressed after prior immune checkpoint inhibitor (ICI) therapy received zimberelimab combined with lenvatinib. The ORR was 33.3%, with a disease control rate of 96.7%. The median PFS was 7.1 months. (trial.medpath.com)

Third-Line Metastatic Colorectal Cancer (mCRC):

The ARC-9 Phase 1b/2 study assessed the combination of etrumadenant, zimberelimab, FOLFOX chemotherapy, and bevacizumab (EZFB) in 75 patients with third-line mCRC. The median OS was 19.7 months, compared to 9.5 months for the control group receiving regorafenib. The median PFS was 6.2 months versus 2.1 months, respectively. The confirmed ORR was 17.3% for EZFB, compared to 2.7% for regorafenib. (stocktitan.net)

Safety

Across clinical trials, zimberelimab has demonstrated a favorable safety profile. In the YH-S001-04 trial for R/R cHL, no serious adverse events with an incidence greater than 5% were reported. (pubmed.ncbi.nlm.nih.gov) In the ARC-9 study for third-line mCRC, the EZFB regimen had a safety profile consistent with the known profiles of each individual component, without unexpected toxicities. A higher percentage of patients treated with regorafenib (17%) had treatment-emergent adverse events leading to discontinuation compared to those treated with EZFB (5%). (stocktitan.net)

Further Reading

• Long-term follow-up of zimberelimab in relapsed or refractory classic Hodgkin lymphoma: Insights from the phase Ⅱ YH-S001-04 clinical trial
• Gloria Biosciences Announces Zimberelimab Approved in China for the Treatment of Recurrent or Metastatic Cervical Cancer
• Zimberelimab Plus Lenvatinib Shows Promise in Advanced Cervical Cancer After ICI Failure
• Gilead and Arcus Announce Etrumadenant Plus Zimberelimab Regimen Significantly Reduced the Risk of Death in Third-line Metastatic Colorectal Cancer

Last updated: Apr 2025

Last updated: Apr 2025

Key Inclusion Criteria:

* Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) guidance

* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1

* Prior systemic radiation or whole brain radiation therapy must have been completed at least 4 weeks before investigational product (IP) administration. Other palliative radiotherapy must be completed 2 weeks before investigational product administration, if radiation therapy-related AEs have resolved to Grade ≤ 1.

* Monotherapy-specific criteria for dose escalation and PD cohorts:

* Dose Escalation: Participants may have any pathologically confirmed advanced or metastatic solid tumor for which standard therapy has proven ineffective, intolerable, or is considered inappropriate.

* Pharmacodynamic Cohorts: Participants may have any pathologically confirmed advanced or metastatic solid tumors for which standard therapy has proven ineffective, intolerable, or is considered inappropriate. Participants must be able to undergo collection of a fresh frozen biopsy during screening, as well as provide an on-treatment fresh frozen biopsy.

* Dose Expansion cohort criteria:

* Histologically confirmed, documented diagnosis of HER2-negative locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma.

* No prior systemic treatment for locally advanced unresectable or metastatic disease.

* Cannot have progressed within 6 months of prior platinum-based chemotherapy for earlier stage disease.

Key Exclusion Criteria:

* Use of any live vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks (28 days) of initiation of study

* Underlying medical conditions or AEs that, in the investigator or sponsor's opinion, will make the administration of the study drugs hazardous

* Any active or documented history of autoimmune disease including but not limited to inflammatory bowel disease, celiac disease, Wegner syndrome, Hashimoto syndrome, systemic lupus erythematosus, scleroderma, sarcoidosis, or autoimmune hepatitis, within 3 years of the first dose of study treatment

* History of trauma or major surgery within 28 days prior to the first dose of study drug

* Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressant medication during study treatment with certain protocol specified exceptions

Note: Other protocol defined Inclusion/Exclusion criteria may apply.