RECRUITING

Phase II Study of Olaparib and Pembrolizumab in Advanced Melanoma With Homologous Recombination (HR) Mutation

Conditions

Metastatic Melanoma Homologous recombination (HR)Mutation Olaparib Pembrolizumab PARP inhibitor anti PD-1 antibody

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This open-label phase II trial studies how well olaparib in combination with pembrolizumab works in treating patients with advanced, metastatic melanoma with the homologous recombination (HR) pathway gene mutation / alteration. Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth, and potentially augment an anti-tumor immune response to pembrolizumab. The trial is designed to assess the efficacy and safety of olaparib in combination with pembrolizumab in patients with HR mutation/ alteration whose disease progressed on prior immunotherapy and/or BRAF-targeting therapy

Official Title

Phase II Study of Olaparib in Combination With Pembrolizumab in Patients With Advanced Melanoma With Homologous Recombination (HR) Pathway Gene Mutation

Quick Facts

Study Start:2021-03-03

Study Completion:2024-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04633902

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Histologically confirmed diagnosis of unresectable or metastatic stage III or IV melanoma * 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 * Disease must be refractory or resistant to anti PD-1 therapy (defined as disease progression within 6 months after the last dose of anti PD-1 antibody therapy) and, for V600 BRAF mutation, disease must be progressed after BRAF inhibitor therapy; or patients could not have tolerated the standard therapies. * Must have measurable disease based on RECIST 1.1. * Must have an ECOG performance status of 0 to 1. * Prior systemic cytotoxic therapy up to 1 regimens is allowed; There is no limit on the number of prior immunotherapy or targeted therapy regimens. * Must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline.	* Previously treated with a PARP inhibitor * Has received prior radiotherapy within 2 weeks of start of study treatment. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease. * 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 7 days prior to the first dose of study drug. * Has a known additional malignancy that is progressing or has required active treatment within the past 2 years * Previous solid organ or allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT) for solid tumors. * Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment. * Has active autoimmune disease that has required systemic treatment in the past 2 years * 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.

Inclusion Criteria

Exclusion Criteria

* Histologically confirmed diagnosis of unresectable or metastatic stage III or IV melanoma
* 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
* Disease must be refractory or resistant to anti PD-1 therapy (defined as disease progression within 6 months after the last dose of anti PD-1 antibody therapy) and, for V600 BRAF mutation, disease must be progressed after BRAF inhibitor therapy; or patients could not have tolerated the standard therapies.
* Must have measurable disease based on RECIST 1.1.
* Must have an ECOG performance status of 0 to 1.
* Prior systemic cytotoxic therapy up to 1 regimens is allowed; There is no limit on the number of prior immunotherapy or targeted therapy regimens.
* Must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline.

* Previously treated with a PARP inhibitor
* Has received prior radiotherapy within 2 weeks of start of study treatment. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
* 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 7 days prior to the first dose of study drug.
* Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
* Previous solid organ or allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT) for solid tumors.
* Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
* Has active autoimmune disease that has required systemic treatment in the past 2 years
* 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.

Contacts and Locations

Study Contact

Kevin B Kim, MD

CONTACT

415-885-8600

ClinicalResearch@sutterhealth.org

Principal Investigator

Kevin B Kim, MD

PRINCIPAL_INVESTIGATOR

California Pacific Medical Center Research Institute

Study Locations (Sites)

California Pacific Medical Center Research Institute

San Francisco, California, 94115

United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: California Pacific Medical Center Research Institute

Kevin B Kim, MD, PRINCIPAL_INVESTIGATOR, California Pacific Medical Center Research Institute

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-03-03

Study Completion Date2024-12-31

Study Record Updates

Study Start Date2021-03-03

Study Completion Date2024-12-31

Terms related to this study

Keywords Provided by Researchers

Homologous recombination (HR)
Mutation
Olaparib
Pembrolizumab
PARP inhibitor
anti PD-1 antibody

Additional Relevant MeSH Terms

Metastatic Melanoma