What side effects are associated with this type of intervention?

Common treatments for melanoma, such as Olaparib (a PARP inhibitor) and Pembrolizumab (a PD-1 inhibitor), have distinct side effect profiles. Olaparib often causes nausea, fatigue, vomiting, and anemia. Pembrolizumab, on the other hand, can lead to immune-related adverse events including skin reactions, endocrine disorders, and pneumonitis. Patients undergoing these treatments should be monitored for these potential side effects to manage them effectively.

What prior FDA approvals exist?

Pembrolizumab, a PD-1 inhibitor, has been approved by the FDA for the treatment of advanced melanoma, demonstrating significant efficacy in patients with high PD-L1 expression. Olaparib, a PARP inhibitor, is approved for cancers with homologous recombination deficiencies, such as BRCA-mutated cancers. The combination of these drugs is being studied to enhance antitumor activity by leveraging both DNA damage response inhibition and immune checkpoint blockade.

What other types of research exist?

Promising novel alternatives to Olaparib and Pembrolizumab for melanoma patients include Ipilimumab (CTLA-4 inhibitor), Nivolumab (PD-1 inhibitor), and the combination of Relatlimab (LAG-3 inhibitor) with Nivolumab. Additionally, Talimogene Laherparepvec (T-VEC) combined with Pembrolizumab has shown potential in clinical trials.

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PARP Inhibitor

Olaparib + Pembrolizumab for Melanoma

Phase 2

Recruiting

Led By Kevin B Kim, MD

Research Sponsored by California Pacific Medical Center Research Institute

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Must have genetic HR mutation/ alteration including ARID1A/B, ARID2, ATM, ATR, BARD1, BRCA1/2, BAP1, BRIP1, CHEK2, FANCA, FANCD2, MRN11A, PALB2, RAD50, RAD51, RAD54B

Histologically confirmed diagnosis of unresectable or metastatic stage III or IV melanoma

Must not have

Has a history of (non-infectious) pneumonitis due to a single agent PD-1 / PD-L1 antibody therapy that required steroids or has current pneumonitis

Previous solid organ or allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT) for solid tumors

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

Summary

This trial is testing a combination of drugs to treat patients with advanced melanoma that has progressed despite other treatments. Olaparib may stop the growth of tumor cells, and pembrolizumab may help the immune system attack the tumor. The trial will assess the safety and effectiveness of the combination.

Who is the study for?

This trial is for adults with advanced melanoma that can't be removed by surgery or has spread, and have specific gene changes called HR mutations. They must have tried immunotherapy and, if they have a BRAF mutation, also BRAF inhibitors without success or couldn't tolerate them. Participants need to be fairly healthy overall and not on high-dose steroids.Check my eligibility

What is being tested?

The study tests the combination of Olaparib, which blocks enzymes helping tumor growth, with Pembrolizumab, an immune system booster against cancer. It's for patients whose melanoma worsened after previous treatments. The goal is to see how effective and safe this drug combo is in these cases.See study design

What are the potential side effects?

Olaparib may cause nausea, vomiting, fatigue, anemia (low red blood cells), and more serious issues like lung problems or blood clots. Pembrolizumab might lead to flu-like symptoms, skin reactions, organ inflammation but could also result in severe immune system attacks on organs.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer has a specific genetic mutation.

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My melanoma cannot be removed by surgery and is in stage III or IV.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I have recovered from side effects of previous treatments to my normal or mild condition.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had lung inflammation from specific cancer treatment that needed steroids.

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I have had an organ, bone marrow, or cord blood transplant for cancer.

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I have an immune system disorder or have been on high-dose steroids or other immune-weakening medicines recently.

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I have an autoimmune disease treated with medication in the last 2 years.

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I have been treated with a PARP inhibitor before.

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I have another cancer that is getting worse or was treated in the last 2 years.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Objective Response Rate (ORR)

Secondary outcome measures

Number of Participants With Adverse Events as a Measure of Safety and Tolerability

Overall survival (OS)

Progression-free survival (PFS)

Trial Design

1Treatment groups

Experimental Treatment

Group I: Olaparib + PembrolizumabExperimental Treatment2 Interventions

This arm will enroll patients who has advanced melanoma with a genetic HR mutation/ alteration including mutation/ deletion in ARID1A/B, ARID2, ATM, ATR, BARD1, BRCA1/2, BAP1, BRIP1, CHEK2, FANCA, FANCD2, MRN11A, PALB2, RAD50, RAD51, RAD54B.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Olaparib

FDA approved

Pembrolizumab

FDA approved

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Olaparib, a PARP inhibitor, blocks the PARP enzyme involved in DNA repair, causing cancer cell death, especially in cells with DNA repair deficiencies. Pembrolizumab, a PD-1 inhibitor, blocks the PD-1 pathway, enhancing the immune system's ability to attack cancer cells. These mechanisms are vital for melanoma patients as they target cancer cells' repair and immune evasion capabilities, improving treatment outcomes.