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Also known as AB122
Zimberelimab · 5 trials · 7 indications
The primary endpoint is change in the number of intratumoral CD8+ T-cells at time of surgery between treatment arm(s) compared to the SBRT + zimberelimab arm (Control Arm B). To obtain CD8+ T-cell count, simple immunohistochemistry (IHC) will be used to quantitate CD8+ T-cells. A designated gastrointestinal (GI) pathologist will review each hematoxylin and eosin (H\&E) stained serial section and IHC slide to oversee the process. Representative areas within the slide will be used for cell counts.
The proportion of patients with Complete Response (CR) + Partial Response (PR), per RECIST v1.1. Complete Response (CR) is defined as disappearance of all target lesions; disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR) is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.
Adverse events will be listed individually by patient and treatment group. The number of patients experiencing each adverse event will be summarized by organ and grade. The number and percentage of patients with adverse events in the different categories will be summarized by treatment group.
| Arm | Type | Description |
|---|---|---|
| Arm A: Safety run-in | EXPERIMENTAL | Prior to resection: SBRT 40 Gy over 5 fractions, zimberelimab (AB122) 240 mg intravenously (IV) every 2 weeks for 7 weeks (4 doses), quemliclustat (AB680) 100 mg IV every 2 weeks for 7 weeks (4 doses) and etrumadenant (AB928) 150 mg PO daily for 7 weeks. After resection: mFOLFIRINOX (4 cycles) |
| Arm B: SBRT with Zimberelimab (AB122) Alone (Control Arm) | ACTIVE_COMPARATOR | Prior to resection: SBRT 40 Gy over 5 fractions, 240 mg IV zimberelimab (AB122) every 2 weeks for 7 weeks (4 doses) prior to surgery. After resection: mFOLFIRINOX (4 cycles) |
| Arm C: SBRT, Zimberelimab with quemliclustat (AB680) | EXPERIMENTAL | Prior to resection: SBRT 40 Gy over 5 fractions, 240 mg IV zimberelimab (AB122) every 2 weeks for 7 weeks (4 doses) prior to surgery in combination with quemliclustat IV at the recommended therapeutic dose (RTD)every 2 weeks for 7 weeks (4 doses) prior to surgery. After resection: mFOLFIRINOX (4 cycles) |
| Arm D: SBRT, Zimberelimab with AB680 and Etrumadenant (AB928) | EXPERIMENTAL | Prior to resection: SBRT 40 Gy over 5 fractions, 240 mg IV zimberelimab (AB122) every 2 weeks for 7 weeks (4 doses) prior to surgery in combination with quemliclustat IV at the RTD every 2 weeks for 7 weeks (4 doses) and etrumadenant (AB928) PO at the RTD daily for 7 weeks prior to surgery. After resection: mFOLFIRINOX (4 cycles) |
| Zimberelimab plus Domvanalimab | EXPERIMENTAL | Treatment Phase 1: Zimberelimab, 360mg, IV, every 3 weeks for 3 cycles. Domvanalimab, 15mg/kg, IV, every 3 weeks for 3 cycles. After 3 cycles, scans will be performed. If it is determined that the cancer is stable or responding patients will continue with Treatment Phase 2. Treatment Phase 2: Zimberelimab, 360mg, IV, every 3 weeks for 3 cycles. Domvanalimab, 15mg/kg, IV, every 3 weeks, for up to 24 months. |
| Cohort A: Zimberelimab + Domvanalimab + Etrumadenant | EXPERIMENTAL | * Patients will be treated on 21-day cycles with 360 mg zimberelimab intravenously on Day 1, 15 mg/kg domvanalimab intravenously on Day 1, and 150 mg etrumadenant orally daily on Days 1 to 21. * Cohort A participants are those that have PD-L1 1-49% |
| Cohort B: Zimberelimab + Domvanalimab + Etrumadenant | EXPERIMENTAL | * Patients will be treated on 21-day cycles with 360 mg zimberelimab intravenously on Day 1, 15 mg/kg domvanalimab intravenously on Day 1, and 150 mg etrumadenant orally daily on Days 1 to 21. * Cohort B participants are those that have PD-L1 ≥ 50%. |
| TMB-H | EXPERIMENTAL | Participants with a tumor biomarker status of TMB-H will receive zimberelimab every 3 weeks. |
| Strata Immune Signature positive | EXPERIMENTAL | Participants with a tumor biomarker status Strata Immune Signature positive will receive zimberelimab every 3 weeks. |
| Zimberelimab (AB 122) + Domvanalimab (AB 154) Safety Cohort (Cohort A) | EXPERIMENTAL | Eligible patients will be sequentially enrolled to receive intravenous domvanalimab (AB 154) combined with zimberelimab (AB 122) (N=6). domvanalimab (AB 154) will be given at a dose of 10 mg/kg and zimberelimab (AB 122) will be given at a dose of 240 mg (flat). |
| Domvanalimab (AB 154) Surgical Cohort (Cohort B1) | EXPERIMENTAL | Candidates for surgical resection will be enrolled and initiate study treatment approximately two weeks prior to the resection. The pre-surgical dose (neoadjuvant treatment) will be double-blinded. B1 (N=10): domvanalimab (AB 154) single agent (10 mg/kg) + placebo Following surgery, all patients will initiate treatment with the combination of domvanalimab (AB 154) and zimberelimab (AB 122). Domvanalimab (AB 154) will be given at a dose of 10 mg/kg and zimberelimab (AB 122) will be given at a dose of 240 mg (flat). |
| Zimberelimab (AB 122) Surgical Cohort (Cohort B2) | EXPERIMENTAL | Candidates for surgical resection will be enrolled and initiate study treatment approximately two weeks prior to the resection. The pre-surgical dose (neoadjuvant treatment) will be double-blinded. B2 (N=10): zimberelimab (AB 122) single agent (240 mg) + placebo Following surgery, all patients will initiate treatment with the combination of domvanalimab (AB 154) and zimberelimab (AB 122). Domvanalimab (AB 154) will be given at a dose of 10 mg/kg and zimberelimab (AB 122) will be given at a dose of 240 mg (flat). |
| Domvanalimab (AB 154) + Zimberelimab (AB 122) Surgical Cohort (Cohort B3) | EXPERIMENTAL | Candidates for surgical resection will be enrolled and initiate study treatment approximately two weeks prior to the resection. The pre-surgical dose (neoadjuvant treatment) will be double-blinded. B3 (N=10): domvanalimab (AB 154, 10 mg/kg) + zimberelimab (AB 122, 240 mg) Following surgery, all patients will initiate treatment with the combination of domvanalimab (AB 154) and zimberelimab (AB 122). Domvanalimab (AB 154) will be given at a dose of 10 mg/kg and zimberelimab (AB 122) will be given at a dose of 240 mg (flat). |
| Placebo Surgical Cohort (Cohort B4) | EXPERIMENTAL | Candidates for surgical resection will be enrolled and initiate study treatment approximately two weeks prior to the resection. The pre-surgical dose (neoadjuvant treatment) will be double-blinded. B4 (N=10): Two placebo infusions Following surgery, all patients will initiate treatment with the combination of domvanalimab (AB 154) and zimberelimab (AB 122). Domvanalimab (AB 154) will be given at a dose of 10 mg/kg and zimberelimab (AB 122) will be given at a dose of 240 mg (flat). |
| Name | Type | Description |
|---|---|---|
| Stereotactic body radiotherapy (SBRT) | RADIATION | SBRT 40 gray (Gy) over 5 fractions |
| Zimberelimab | DRUG | 240 mg intravenously (IV) |
| Quemliclustat | DRUG | 100 mg IV |
| Etrumadenant | DRUG | 150 mg orally |
| Modified FOLFIRINOX | DRUG | * Oxaliplatin 85 mg per square meter IV * Irinotecan 150 mg per square meter IV * Leucovorin 400 mg per square meter IV * Fluorouracil 2400 mg per square meter IV * Pegfilgrastim injector kit (6mg subcutaneous) |
| Domvanalimab | DRUG | Domvanalimab is a humanized immunoglobulin G1 (IgG1) mAb that targets immune checkpoint TIGIT. |
| Placebo | DRUG | Saline placebo comparator for pre-surgery treatment in cohort B4 |
Inclusion Criteria: * Histological or pathological confirmation of pancreatic adenocarcinoma Cytologic or histologic proof of pancreatic ductal adenocarcinoma (PDAC) needs to be verified by the treating institution pathologist. A pathological report from non-treating institutions is sufficient to c...
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Zimberelimab is an investigational monoclonal antibody being studied in oncology for advanced solid tumors, glioblastoma, melanoma, non small cell lung cancer, and pancreatic ductal adenocarcinoma. It is being developed by Arcus Biosciences, Inc. and is not yet approved for commercial use. Clinical testing is ongoing across these tumor types.
Zimberelimab targets PDCD1, also known as PD-1, and acts as an inhibitor of this receptor. By binding PDCD1, it is designed to interfere with PD-1 mediated signaling in the tumor microenvironment. This mechanism places it in the checkpoint inhibitor class of monoclonal antibody cancer therapies.
Zimberelimab is being developed by Arcus Biosciences, Inc., which trades under the ticker RCUS. The company is running clinical studies of the antibody both as a single agent and in combination with other investigational agents from its pipeline, including domvanalimab and etrumadenant.
Zimberelimab is in clinical development and is investigational. Trials registered for the drug span early phase 1 and phase 2, with the phase 2 studies being the most advanced stage of testing described. It has not been approved by the FDA for any indication.
Registered trials include NCT06048484 in localized pancreatic ductal adenocarcinoma, NCT05130177 in PD-1 relapsed or refractory melanoma, NCT04791839 in previously treated non small cell lung cancer, and NCT04656535 in recurrent glioblastoma. These studies evaluate zimberelimab alone or in combination with other agents.
Yes, zimberelimab is also known as AB122. The AB122 designation appears in several trial titles, including the melanoma study with domvanalimab (AB154) and the glioblastoma study combining AB154 with AB122. Both names refer to the same anti-PDCD1 monoclonal antibody developed by Arcus Biosciences.