NCT04656535

AB154 Combined With AB122 for Recurrent Glioblastoma

A Multi-Center Phase 0/I Trial of Anti-TIGIT Antibody AB154 in Combination With Anti-PD-1 Antibody AB122 for Recurrent Glioblastoma.

• Status: Active Not Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 46 (estimated)
• Sponsor: Yale University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a phase 0/I exploratory study. Patients at first or second recurrence of glioblastoma will be enrolled. The study will be divided into two cohorts: Cohort A (safety cohort) and Cohort B (surgical patient cohort). Cohort A: Eligible patients will be sequentially enrolled to receive intravenous domvanalimab combined with zimberelimab (N=6). Domvanalimab will be given at a dose of 10 mg/kg and zimberelimab will be given at a dose of 240 mg (flat). The dosing was determined in a separate study in solid tumors; this cohort will confirm the safety of the dosing schedule in patients with brain tumors. Cohort B: Expansion surgical cohort. The purpose of cohort B is to provide an additional safety evaluation of domvanalimab + zimberelimab as well as tissue and blood for exploratory ancillary studies investigating the effects of domvanalimab + zimberelimab in the tumor and tumor microenvironment. A total of 46 patients will be enrolled in this cohort.

Detailed description

This is a phase 0/I exploratory study. Patients at first or second recurrence of glioblastoma will be enrolled. The study will be divided into two cohorts: Cohort A (safety cohort) and Cohort B (surgical patient cohort). Cohort A: Eligible patients will be sequentially enrolled to receive intravenous domvanalimab combined with zimberelimab (N=6). Domvanalimab will be given at a dose of 10 mg/kg and zimberelimab will be given at a dose of 240 mg (flat). The dosing was determined in a separate study in solid tumors; this cohort will confirm the safety of the dosing schedule in patients with brain tumors. Cohort B: Expansion surgical cohort. The purpose of cohort B is to provide an additional safety evaluation of domvanalimab + zimberelimab as well as tissue and blood for exploratory ancillary studies investigating the effects of domvanalimab + zimberelimab in the tumor and tumor microenvironment. A total of 46 patients will be enrolled in this cohort. Following completion of cohort A, patients who are candidates for surgical resection for management of tumor progression (i.e. need for diagnostic confirmation or tumor debulking) will be enrolled prior to surgical resection, and initiate study treatment approximately two weeks prior to the resection. Patients will be randomized to one of the four treatment arms and initiate treatment prior to surgery, according to treatment assignment. The pre-surgical dose (neoadjuvant treatment) will be double-blinded, to minimize dropouts. A total of 10 patients will be allocated to each one of the following groups in a blinded fashion, approximately two weeks before surgery: * B1 (N=10): domvanalimab single agent (10 mg/kg) + placebo * B2 (N=10): zimberelimab single agent (240 mg) + placebo * B3 (N=10): domvanalimab (10 mg/kg) +zimberelimab (240 mg) * B4 (N=10): Two placebo infusions Two to six weeks, following surgery, all patients (N=46) will be re-screened and if still eligible will initiate treatment with the combination of domvanalimab and zimberelimab.

Conditions

• Glioblastoma

Interventions

Type	Name	Description
DRUG	Zimberelimab	Zimberelimab (AB122) is a fully human immunoglobulin G4 (hIgG4) monoclonal antibody (mAb) that targets PD-1.
DRUG	Domvanalimab	Domvanalimab (AB 154) is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that targets TIGIT.
DRUG	Placebo	Saline placebo comparator for pre-surgery treatment in cohort B4

Timeline

• Start date: 2021-04-21
• Primary completion: 2026-03-17
• Completion: 2026-12-31
• First posted: 2020-12-07
• Last updated: 2026-04-17

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study