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

NCT04633902 | Unknown Phase 2 FDA Drug

• 1 other identifier: CPMC19-MEL01
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR of olaparib in combination with pembrolizumab in patients with advanced melanoma with genetic homologous recombination (HR) mutation/ alteration using RECIST v1.1

  6 months

Secondary Outcomes (3)

• Progression-free survival (PFS)

  2 years

• Overall survival (OS)

  2 years

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

  2 years

Study Arms (1)

Olaparib + Pembrolizumab

EXPERIMENTAL

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.

Drug: Olaparib; Drug: Pembrolizumab

Interventions

Olaparib DRUG

Olaparib 300 mg BID daily

Also known as: Lynparza

Olaparib + Pembrolizumab

Pembrolizumab DRUG

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

Also known as: Keytruda

Olaparib + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• California Pacific Medical Center Research Institute: lead
• M.D. Anderson Cancer Center: collaborator

Study Sites (2)

California Pacific Medical Center Research Institute

San Francisco, California, 94115, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

olaparib; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Kevin B Kim, MD

  California Pacific Medical Center Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kevin B Kim, MD

CONTACT

415-885-8600; ClinicalResearch@sutterhealth.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2020
• First Posted: November 18, 2020
• Study Start: March 3, 2021
• Primary Completion: June 30, 2023
• Study Completion: December 31, 2024
• Last Updated: December 6, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)