Phase II Study of Olaparib and Pembrolizumab in Advanced Melanoma with HR Mutation

Sponsor: California Pacific Medical Center Research Institute

Sponsor score: 0
Inactive

ClinicalTrials ID:NCT04633902

Provider View

This clinical trial is exploring the effectiveness of combining two drugs, olaparib and pembrolizumab, to treat patients with advanced melanoma that has a specific genetic mutation affecting DNA repair. The study aims to see if this combination can help control the cancer in patients whose disease has progressed despite previous treatments.

Patient Parameters

Program Overview

This study is testing a combination of two drugs, olaparib and pembrolizumab, to see if they can work together to treat advanced melanoma in patients with a specific genetic mutation in the homologous recombination (HR) pathway. Olaparib may help stop cancer cells from growing by blocking certain enzymes, while pembrolizumab helps the immune system attack cancer cells. The trial will evaluate how well this combination works and how safe it is for patients whose melanoma has not responded to previous treatments, including immunotherapy and BRAF-targeting therapy.

Description

This clinical trial is investigating a new treatment approach for advanced melanoma, a type of skin cancer, in patients with specific genetic mutations that affect DNA repair. The treatment involves using a drug called olaparib, which targets cancer cells with DNA repair issues, and pembrolizumab, which boosts the immune system's ability to fight cancer.

The study focuses on patients with mutations in genes related to the homologous recombination (HR) pathway, such as BRCA1, BRCA2, and others. These mutations are common in melanoma and may make the cancer more sensitive to the effects of olaparib. The trial will assess whether this combination can effectively shrink tumors and improve outcomes for patients whose cancer has progressed after previous treatments.

Participants will receive olaparib daily and pembrolizumab every three weeks for up to two years, or until the cancer progresses or side effects become too severe. The study aims to provide new insights into the potential benefits of combining these two drugs for treating advanced melanoma.

Eligibility Criteria

Inclusion Criteria

  • Diagnosed with advanced melanoma that cannot be surgically removed or has spread to other parts of the body (stage III or IV).
  • Have a genetic mutation in the HR pathway, including genes like ARID1A, BRCA1, BRCA2, and others.
  • Cancer must have progressed after treatment with anti-PD-1 therapy, and for those with a BRAF mutation, after BRAF inhibitor therapy, or if standard treatments were not tolerated.
  • Have measurable cancer that can be tracked using standard criteria.
  • Be in good overall health with an ECOG performance status of 0 or 1, meaning fully active or restricted in physically strenuous activity but ambulatory.
  • Have had no more than one prior chemotherapy regimen, with no limit on previous immunotherapy or targeted therapy regimens.
  • Have recovered from any side effects of previous treatments to a mild level or baseline.

Exclusion Criteria

  • Previously treated with a PARP inhibitor.
  • Received radiation therapy within two weeks before starting the study treatment, except for short-term palliative radiation.
  • Have an immune system deficiency or are taking high doses of steroids or other immunosuppressive drugs.
  • Have another active cancer that has required treatment in the past two years.
  • Have had a solid organ or bone marrow transplant.
  • Have active cancer spread to the brain or spinal cord, unless previously treated and stable.
  • Have an active autoimmune disease requiring treatment in the past two years.
  • Have a history of lung inflammation due to PD-1/PD-L1 therapy that required steroids or have current lung inflammation.

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