Zimberelimab + Domvanalimab for Melanoma

Overseen By Amy Rose, RN, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

26 Participants Needed

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}

Research Team

Diwakar Davar, MD

Principal Investigator

UPMC Hillman Cancer Center

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.

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

Treatment Details

Interventions

• Domvanalimab
• Zimberelimab

Trial Overview 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.

Participant Groups

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.

Who Is Running the Clinical Trial?

Diwakar Davar

Lead Sponsor

Trials

12

Recruited

420+

Arcus Biosciences, Inc.

Industry Sponsor

Trials

44

Recruited

7,500+

Findings from Research

Tremelimumab, a monoclonal antibody, has shown the ability to induce durable tumor regressions in 7% to 10% of patients with metastatic melanoma, with effects lasting up to 8 years, primarily through the activation of cytotoxic T lymphocytes.

While tremelimumab can lead to significant tumor responses, it also carries a risk of severe toxicities (20% to 25% of patients), mainly due to inflammatory or autoimmune reactions from its mechanism of action, which involves inhibiting CTLA-4 to enhance immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical development of the anti-CTLA-4 antibody tremelimumab. Ribas, A.[2021]

In a review of 143 patients with advanced melanoma treated with tremelimumab, a CTLA-4 antibody, the median overall survival was 13 months, with some patients surviving over 12 years, indicating potential for long-term benefits from this treatment.

The study found an objective response rate of 15.6% with a median duration of response lasting 6.5 years, suggesting that tremelimumab can provide sustained anti-tumor effects in a subset of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long term survival with cytotoxic T lymphocyte-associated antigen 4 blockade using tremelimumab. Eroglu, Z., Kim, DW., Wang, X., et al.[2023]

In a phase III trial involving 655 patients with advanced melanoma, tremelimumab did not show a statistically significant improvement in overall survival compared to standard chemotherapy, with median survival times of 12.6 months for tremelimumab versus 10.7 months for chemotherapy.

Although the objective response rates were similar between the two treatments, patients receiving tremelimumab experienced a significantly longer duration of response (35.8 months) compared to those on chemotherapy (13.7 months), indicating potential benefits in long-term treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III randomized clinical trial comparing tremelimumab with standard-of-care chemotherapy in patients with advanced melanoma. Ribas, A., Kefford, R., Marshall, MA., et al.[2022]

In a phase II study involving 251 patients with refractory melanoma, tremelimumab demonstrated an objective response rate of 6.6%, with responses lasting between 8.9 to 29.8 months, indicating its potential effectiveness in treating this type of cancer.

The treatment was generally well-tolerated, with most adverse events being mild to moderate; however, there were some serious side effects, including grade 3/4 diarrhea and colitis, and 2 treatment-related deaths, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of tremelimumab (CP-675,206) in patients with advanced refractory or relapsed melanoma. Kirkwood, JM., Lorigan, P., Hersey, P., et al.[2022]

In a phase 2 trial involving 40 patients with malignant mesothelioma, the combination of tremelimumab and durvalumab resulted in an immune-related objective response in 28% of patients, with a median response duration of 16.1 months, indicating promising efficacy for this treatment approach.

The treatment was generally well-tolerated, with 75% of patients experiencing treatment-related adverse events, mostly manageable and reversible, suggesting a favorable safety profile for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tremelimumab combined with durvalumab in patients with mesothelioma (NIBIT-MESO-1): an open-label, non-randomised, phase 2 study. Calabrò, L., Morra, A., Giannarelli, D., et al.[2019]

References

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

Clinical development of the anti-CTLA-4 antibody tremelimumab. [2021]

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

Long term survival with cytotoxic T lymphocyte-associated antigen 4 blockade using tremelimumab. [2023]

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]

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]

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]