Olaparib in Combination With Pembrolizumab for Advanced Uveal Melanoma

NCT05524935 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: MCC-2173158050
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

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.

Conditions

Uveal Melanoma; Ocular Melanoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  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.

  up to 24 months

Secondary Outcomes (3)

• Progression Free Survival (PFS)

  up to 24 months

• Overall Survival (OS)

  up to 24 months

• Number of Adverse Events related to study treatment

  up to 24 months

Study Arms (1)

Pembrolizumab and Olaparib

EXPERIMENTAL

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

Drug: Pembrolizumab; Drug: Olaparib

Interventions

Pembrolizumab DRUG

Pembrolizumab Day 1 of each 21 day (3 week) cycle

Also known as: Keytruda

Pembrolizumab and Olaparib

Olaparib DRUG

Olaparib by mouth days 1-21 of each 21 day (3 week) cycle

Also known as: AZD2281, KU-0059736, Lynparza

Pembrolizumab and Olaparib

Eligibility Criteria

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

You may qualify if:

• 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 1.
• Have the ability to swallow oral medications (olaparib).
• Have adequate organ function as defined in the protocol.

You may not qualify if:

• 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 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.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: this is by history; testing is not required unless clinically suspected
• Has a known history of active Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA is detected) infection. Note: testing for Hepatitis B and Hepatitis C is not required unless clinically indicated or mandated by local health authority.
• Has a known history of active tuberculosis.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Uveal Melanoma

Interventions

pembrolizumab; olaparib

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Study Officials

• Nikhil I Khushalani, MD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maureen Canelo

CONTACT

813-745-4277; Maureen.Canelo@moffitt.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: August 30, 2022
• First Posted: September 1, 2022
• Study Start: October 11, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 1, 2026

Record last verified: 2026-03

Locations

US (1)