Zimberelimab + Domvanalimab for Melanoma

Recruiting in Palo Alto (17 mi)

Overseen by Diwakar Davar, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Diwakar Davar

Must be taking: Anti-PD-1/L1 mAb

Must not be taking: Immunosuppressants, Steroids, Chemotherapy, others

Disqualifiers: Non-cutaneous melanoma, Immunodeficiency, Autoimmune, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain immunosuppressive therapies or have recently received chemotherapy, targeted therapy, or small molecule therapy within 2 weeks before the study starts.

What makes the drug Zimberelimab + Domvanalimab unique for treating melanoma?

Zimberelimab + Domvanalimab is unique because it combines two different types of immune checkpoint inhibitors, which are drugs that help the immune system recognize and attack cancer cells. This combination targets different pathways in the immune system, potentially offering a new approach for treating melanoma compared to existing treatments.

^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults with a confirmed diagnosis of cutaneous melanoma who have previously not responded to anti-PD-1/L1 mAb treatments. They must have measurable disease, be able to provide a biopsy, and have good organ function and performance status. Women can't be pregnant or breastfeeding and must use contraception; men also need to use contraception.

Inclusion Criteria

My organs are functioning well.

My condition worsened despite treatment with an anti-PD-1/L1 medication.

I agree to use contraception and not donate sperm during the treatment.

Exclusion Criteria

I have not had another type of cancer besides blood cancer in the last 3 years.

I have or had lung inflammation that needed steroids.

I have been treated for an autoimmune disease in the last 2 years.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment Phase 1

Participants receive zimberelimab 360 mg and domvanalimab 15 mg/kg every 3 weeks for 3 cycles, followed by restaging scans

9 weeks

3 visits (in-person)

Treatment Phase 2

Participants continue to receive zimberelimab and domvanalimab every 3 weeks until disease progression, intolerable toxicity, or up to 24 months

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Participant Groups

The study tests the combination of Zimberelimab (AB122) with Domvanalimab (AB154) in patients whose melanoma has not improved after PD-1 inhibitor therapy. The main goal is to see how many patients experience a reduction in their cancer size as a response to this treatment combo.

Group I: Zimberelimab plus Domvanalimab Experimental Treatment 2 Interventions

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

UPMC Hillman Cancer Center Pittsburgh, PA

Who Is Running the Clinical Trial?

Diwakar Davar Lead Sponsor

Arcus Biosciences, Inc. Industry Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Clinical development of the anti-CTLA-4 antibody tremelimumab. [2021] Tremelimumab (formerly CP-675,206) is a fully human IgG2 monoclonal antibody tested in patients with cancer, of whom the majority have had metastatic melanoma. Clinical trials using tremelimumab demonstrate that this antibody can induce durable tumor regressions (up to 8 years at this time) in 7% to 10% of patients with metastatic melanoma. These tumor responses are mediated by the intratumoral infiltration of cytotoxic T lymphocytes (CTLs) as demonstrated in patient-derived tumor biopsies. Grade 3 or 4 toxicities in the range of 20% to 25% are mainly inflammatory or autoimmune in nature, which are on-target effects after inhibiting CTLA-4-mediated self-tolerance. The lack of survival advantage in the early analysis of a phase III clinical trial comparing tremelimumab with standard chemotherapy for metastatic melanoma highlights the importance of gaining a better understanding of how this antibody modulates the human immune system and how to better select patients for this mode of therapy.

2. England pubmed.ncbi.nlm.nih.gov

Long term survival with cytotoxic T lymphocyte-associated antigen 4 blockade using tremelimumab. [2023] One of the hallmarks of cancer immunotherapy is the long duration of responses, evident with cytokines like interleukin-2 or a variety of cancer vaccines. However, there is limited information available on very long term outcomes of patients treated with anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibodies. Tremelimumab is an anti-CTLA-4 antibody of immunoglobulin G2 (IgG2) isotype initially tested in patients with advanced melanoma over 12 years ago.

3. United States pubmed.ncbi.nlm.nih.gov

Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. [2022] In phase I/II trials, the cytotoxic T lymphocyte-associated antigen-4-blocking monoclonal antibody tremelimumab induced durable responses in a subset of patients with advanced melanoma. This phase III study evaluated overall survival (OS) and other safety and efficacy end points in patients with advanced melanoma treated with tremelimumab or standard-of-care chemotherapy.

4. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of tremelimumab (CP-675,206) in patients with advanced refractory or relapsed melanoma. [2022] This phase II study assessed the antitumor activity of tremelimumab, a fully human, anti-CTL-associated antigen 4 monoclonal antibody, in patients with melanoma.

5. England pubmed.ncbi.nlm.nih.gov

Tremelimumab combined with durvalumab in patients with mesothelioma (NIBIT-MESO-1): an open-label, non-randomised, phase 2 study. [2019] Tremelimumab, an anti-CTLA4 monoclonal antibody, initially showed good activity when used alone in patients with mesothelioma, but did not improve the overall survival of patients who failed on first-line or second-line chemotherapy compared with placebo in the DETERMINE study. We aimed to investigate the efficacy and safety of first-line or second-line tremelimumab combined with durvalumab, an anti-PD-L1 monoclonal antibody, in patients with malignant mesothelioma.