Pembrolizumab and Olaparib Treatment for Relapsed or Refractory Peripheral T-Cell Lymphoma

Inclusion Criteria:

1. Male/female participants who are at least 21 years of age on the day of signinginformed consent with histologically or cytologically-confirmed diagnosis ofperipheral T-cell lymphoma (PTCL), including angioimmunoblastic T-cell lymphoma (AITL), peripheral T-cell lymphoma of T-follicular helper cell derivation (PTCL-TFH), anaplastic large cell lymphoma (ALCL), NK/T-cell lymphoma (NKTCL),gamma-delta T cell lymphoma (GDTL), enteropathy associated T-cell lymphoma (EATL),monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), subcutaneouspanniculitis like T-cell lymphoma, and PTCL, not otherwise specified (PTCL-NOS) willbe enrolled in this study.

2. Male participants: A male participant must agree to use a contraception as detailed in Appendix 3 ofthis protocol during the treatment period and for at least the time needed toeliminate the study intervention (180 days for Olaparib; no requirement forpembrolizumab) after the last dose of study treatment and refrain from donatingsperm during this period.

3. 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. Nota woman of childbearing potential (WOCBP) as defined in Appendix 3 OR b. A WOCBP whoagrees to follow the contraceptive guidance in Appendix 3 during the treatmentperiod and for at least the time needed to eliminate the study intervention (180days for Olaparib; 120 days for pembrolizumab) after the last dose of studytreatment.

4. Participants must have progressed on treatment with at least one prior systemicanti-cancer therapy including investigational agents. These may include ananti-PD-1/L1 mAb administered either as monotherapy or in combination with othercheckpoint inhibitors or other therapies. PD-1 treatment progression is defined bymeeting all of the following criteria:

5. Has received at least 2 doses of an approved anti-PD-1/L1 mAb.

6. Has demonstrated disease progression after anti-PD-1/L1 as defined by Chesonresponse criteria. The initial evidence of PD is to be confirmed by a secondassessment no less than 4 weeks from the date of the first documented diseaseprogression, in the absence of rapid clinical progression (as defined in 4.c).

7. Progressive disease has been documented within 12 weeks from the last dose ofanti-PD-1/L1 mAb.

• Progressive disease is determined according to Cheson response criteria.
• This determination is made by the investigator. Once disease progressionis confirmed, the initial date of disease progression documentation willbe considered the date of disease progression. Progression on other systemic anti-cancer therapy including investigational agentsis defined by radiographic disease progression based on Cheson response criteria.

5. The participant (or legally acceptable representative if applicable) provideswritten informed consent for the trial.

6. Have measurable disease based on Cheson criteria. Lesions situated in a previouslyirradiated area are considered measurable if progression has been demonstrated insuch lesions.

7. Archival tumor tissue sample or newly obtained [core, incisional or excisional]biopsy of a tumor lesion not previously irradiated has been provided.Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.Newly obtained biopsies are preferred to archived tissue.

8. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.Evaluation of ECOG is to be performed within 7 days prior to the first dose of studyintervention.

9. Have adequate organ function as defined in the following. Specimens must becollected within 10 days prior to the start of study intervention.

• Absolute neutrophil count (ANC)≥500/μL

• Platelets ≥25 000/μL

• Hemoglobin ≥8 g/dL

• Creatinine OR Measured or calculated creatinine clearance (GFR can also be usedin place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant withcreatinine levels >1.5 × institutional ULN

• Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with totalbilirubin levels >1.5 × ULN

• AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with livermetastases)

• International normalized ratio (INR) OR prothrombin time (PT) ≤1.5 × ULN unlessparticipant is receiving anticoagulant therapy as long as PT or PTT is withintherapeutic range of intended use of anticoagulants

• Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant isreceiving anticoagulant therapy as long as PT or PTT is within therapeuticrange of intended use of anticoagulants

10. Hepatitis B and C screening tests are required:

• Hepatitis B positive subjects

• Participants who are HBsAg positive are eligible if they have received HBVantiviral therapy for at least 4 weeks and have undetectable HBV viralload prior to enrolment.

• Participants should remain on anti-viral therapy throughout studyintervention and follow local guidelines for HBV anti-viral therapy postcompletion of study intervention.

• Participants with history of HCV infection are eligible if HCV viral load isundetectable at screening.

• Participants must have completed curative anti-viral therapy at least 4weeks prior to enrolment.

11. Participant has a life expectancy of at least 3 months

Exclusion Criteria:

1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment (see Appendix 3). If the urine test is positive or cannot be confirmed as negative,a serum pregnancy test will be required.

2. Has received prior systemic investigational agents within 4 weeks (or shorterinterval for kinase inhibitors or other short half-life drugs, per investigatordiscretion) or has used an investigational device within 4 weeks prior to treatment.

3. Has received prior radiotherapy within 2 weeks of start of study intervention orradiation-related toxicities requiring corticosteroids. Note: Two weeks or fewer ofpalliative radiotherapy for non-CNS disease, with a 1-week washout, is permitted.

4. Has received a live vaccine or live-attenuated vaccine within 30 days before thefirst dose of study intervention. Administration of killed vaccines is allowed.

5. 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 ofimmunosuppressive therapy within 7 days prior to the first dose of study drug.

6. Known additional malignancy that is progressing or has required active treatmentwithin the past 3 years. Note: Participants with basal cell carcinoma of the skin,squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma insitu of the bladder that have undergone potentially curative therapy are notexcluded.

7. Has known active CNS metastases and/or carcinomatous meningitis. Participants withpreviously treated brain metastases may participate provided they are radiologicallystable, 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 daysprior to first dose of study intervention.

8. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of itsexcipients.

9. Has active autoimmune disease that has required systemic treatment in the past 2years except replacement therapy (e.g., thyroxine, insulin, or physiologiccorticosteroid)

10. Has a history of (non-infectious) pneumonitis/interstitial lung disease thatrequired steroids or has current pneumonitis/interstitial lung disease.

11. Has an active infection requiring systemic therapy.

12. Has a known history of Human Immunodeficiency Virus (HIV) infection.

13. Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA)and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA)infection. Note: HIV, Hepatitis B and C screening tests are required.

14. Has not adequately recovered from major surgery or has ongoing surgicalcomplications.

15. Has a history or current evidence of any condition, therapy, or laboratoryabnormality or other circumstance that might confound the results of the study,interfere with the participant's participation for the full duration of the study,such that it is not in the best interest of the participant to participate, in theopinion of the treating investigator.

16. Has known psychiatric or substance abuse disorders that would interfere withcooperation with the requirements of the trial.

17. Is pregnant or breastfeeding or expecting to conceive or father children within theprojected duration of the study, starting with the screening visit through 180 daysafter the last dose of trial treatment.

18. Has had an allogenic tissue/solid organ transplant.