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

NCT05130177 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCC 21-150
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The main goal of this study is to establish the proportion of patients with objective response to zimberelimab/domvanalimab in PD-1 R/R melanoma patients.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  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.

  Up to 3 years

Secondary Outcomes (8)

• Objective Response Rate (ORR) (iRECIST)

  Up to 3 years

• 6-month Progression-free Survival (PFS)

  Up to 6 months

• Progression-free Survival (PFS)

  Up to 5 years

• Overall Survival (OS)

  Up to 5 years

• 1-year Progression-free Survival (PFS)

  Up to 1 year

Study Arms (1)

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.

Drug: Zimberelimab; Drug: Domvanalimab

Interventions

Zimberelimab DRUG

Zimberelimab is a fully human immunoglobulin G4 (hIgG4) monoclonal antibody (mAb) that targets the human programmed cell death-1 (PD-1) immune checkpoint.

Also known as: AB122

Zimberelimab plus Domvanalimab

Domvanalimab DRUG

Domvanalimab is a humanized immunoglobulin G1 (IgG1) mAb that targets immune checkpoint TIGIT.

Also known as: AB154

Zimberelimab plus Domvanalimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of cutaneous melanoma (or unknown primary) will be enrolled in this study.
• Male participants: A male participant must agree to use a contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP); OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
• Participants must have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria:
• Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
• Participants who progressed on/within 3 months of adjuvant therapy with anti-PD-(L)1 inhibitor will be allowed.
• Has demonstrated disease progression after anti-PD-1/L1 as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment no less than 4 weeks from the date of the first documented PD, in the absence of rapid clinical progression (as defined in 4.c).
• Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb.
• Progressive disease as determined above. This determination is made by the treating investigator. Once PD is confirmed, the initial date of PD documentation will be considered the date of PD. Anti-PD/L1 mAb need not be the most recent line of therapy administered.
• Prior treatment with an anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody is allowed but not required.
• Prior treatment with BRAF/MEK inhibitor therapy (if BRAF mutated) is allowed but not required.
• The participant provides written informed consent for the trial.
• Presence of measurable disease based on RECIST 1.1.

You may not qualify if:

• Receipt of prior agent(s) targeting components of the TIGIT/CD226 pathway including but not limited to CD226, TIGIT, PVR/CD155 and CD112.
• Diagnosis of non-cutaneous melanoma histologies including mucosal melanoma, ocular/choroidal melanoma, acral-lentiginous melanoma.
• Diagnosis of immunodeficiency, immunosuppression and/or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Prior chemotherapy, targeted therapy, and/or small molecule therapy within 2 weeks (or 4 half lives) prior to study Day 1.
• Patients who have not recovered (i.e., ≤Grade 1 or at baseline or ≤Grade 2 endocrinopathy) from adverse events (AEs) due to a previously administered agent.
• Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
• \--- A 2-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• A WOCBP who has a positive urine pregnancy test at Screening. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has received a live vaccine within 30 days prior to the first dose of study drug.
• Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine.
• Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose of study drug.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• \--- Note: Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Concurrent non-hematologic malignancy within 3 years of data of first planned dose of therapy except for tumors with a negligible risk of metastasis and/or death as defined below:

Sponsors & Collaborators

• Diwakar Davar: lead
• Arcus Biosciences, Inc.: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

zimberelimab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Diwakar Davar, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: November 10, 2021
• First Posted: November 23, 2021
• Study Start: March 16, 2022
• Primary Completion: February 6, 2026
• Study Completion (Estimated): January 31, 2030
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)