Recruiting
Phase 2

Olaparib & Pembrolizumab

Sponsor:

California Pacific Medical Center Research Institute

Code:

NCT04633902

Conditions

Metastatic Melanoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Olaparib

Pembrolizumab

Study Details

Brief summary:

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

Conditions

Metastatic Melanoma

Study ID

NCT04633902

Start date

Mar 3, 2021

Status verified date

Dec, 2022

Completion date

Dec 31, 2024

Anticipated

Primary completion date

Jun 30, 2023

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion 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.

Exclusion Criteria:

  • 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.

Study Design

Enrollment

41 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Olaparib + Pembrolizumab

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.

Interventions

Olaparib

Olaparib 300 mg BID daily

Pembrolizumab

Pembrolizumab 200 mg IV eveyr 3 weeks (for up to 2 years)

Primary outcome measure

  • Objective Response Rate (ORR) [ Time Frame: 6 months ]

Central Contacts and Locations

Central contacts

Kevin B Kim, MD

415-885-8600ClinicalResearch@sutterhealth.org

Locations

California Pacific Medical Center Research Institute

Recruiting

San Francisco, California, United States, 94115

The University of Texas MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Debbie Stroughter

713-792-7734CR_Study_Registration@mdanderson.org

Principal Investigator:

Sapna Patel, MD

More Information

Sponsor

California Pacific Medical Center Research Institute

Last update posted

Dec 6, 2022

Last verified

Dec, 2022

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by California Pacific Medical Center Research Institute on 2022-12-06.