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 1.
- - 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.
- - 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.
- - Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the subject's
participation for the full duration of the study, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
- - Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
- - Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of trial treatment.
- - Has had an allogenic tissue/solid organ transplant.
