A Phase II Trial of Olaparib in Combination With Pembrolizumab for Advanced Uveal Melanoma

H. Lee Moffitt Cancer Center and Research Institute2 sites in 1 country37 target enrollmentOctober 11, 2022

ConditionsUveal Melanoma Ocular Melanoma

InterventionsPembrolizumab Olaparib

DrugsPembrolizumab Olaparib

Overview

Phase: Phase 2
Intervention: Pembrolizumab
Conditions: Uveal Melanoma
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Enrollment: 37
Locations: 2
Primary Endpoint: Overall Response Rate (ORR)
Status: Recruiting
Last Updated: 3 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a prospective phase II multi-center trial of the combination of the PARP inhibitor olaparib with the immune checkpoint inhibitor pembrolizumab in advanced uveal melanoma.

Registry

clinicaltrials.gov

Start Date

October 11, 2022

End Date

December 1, 2027

Last Updated

3 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Male or female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of metastatic uveal melanoma will be enrolled in this study. Prior hepatic directed therapy for metastatic uveal melanoma is permitted.
•Male participants: A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 200 days after the last dose of study treatment and refrain from donating sperm during this period.
•Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies: (a) Not a woman of childbearing potential (WOCBP) as defined in Appendix 3, OR (b) A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days after the last dose of study treatment.
•The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
•Have measurable disease based on RECIST 1.1.49 Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
•Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
•Have the ability to swallow oral medications (olaparib).
•Have adequate organ function as defined in the protocol.

Exclusion Criteria

•A woman of childbearing potential (WOCBP) who has a positive urine or serum pregnancy test within 72 hours prior to start of study therapy. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
•Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent as monotherapy or as combination therapy for uveal melanoma. Note: these agents may have been used for the treatment of another malignancy as long as the therapy was completed more than 2 years ago (calculated from the date of signing the ICF).
•Has received prior PARP inhibitor therapy.
•Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks \[or 5 half-lives of the agent, whichever is shorter\] prior to planned start of study therapy. Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline (with the exception of endocrine toxicity requiring replacement therapy which is permissible)
•Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
•Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
•Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent; for CNS metastases, see permissible steroid dosing in exclusion criterion #9 below) 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 requires active treatment, the lack of which would pose a risk to the health of the subject, in the opinion of the investigator.
•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 using no more than the equivalent of 2mg daily of dexamethasone (or equivalent corticosteroid).
•Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.

Arms & Interventions

Pembrolizumab and Olaparib

Participants will be given 200 mg Pembrolizumab IV every 21 days + will take 300 mg Olaparib by mouth twice daily days 1-21 of each 21 day cycle. Treatment will continue until progression, unacceptable toxicity, or for a maximum of 35 treatment cycles

Intervention: Pembrolizumab

Pembrolizumab and Olaparib

Intervention: Olaparib

Outcomes

Primary Outcomes

Overall Response Rate (ORR)

Time Frame: up to 24 months

Overall Response Rate is defined as the rate of the best overall response as complete response (CR) +partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.