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

NCT06160843 | Recruiting Phase 2

• 1 other identifier: POLAR
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the efficacy and safety of Pembrolizumab in combination with Olaparib in participants with relapsed/refractory Peripheral T-cell Lymphoma (PTCL). The study mainly aims to evaluate:

• objective response rate (ORR) as per Cheson response criteria assessed by the independent central review
• overall survival and progression-free survival
• adverse events by CTCAE version 5.0 The administration of Pembrolizumab and Olaparib to participants will occur on Day 1 of each 3-week dosing cycle and will continue until disease progression or unacceptable toxicity, up to 35 cycles. Treatment with Olaparib will proceed continuously from Day 1 of Cycle 1, in 3-week dosing cycles in parallel with Pembrolizumab, up to 35 cycles, unless specific withdrawal/discontinuation criteria are met. After the end of treatment, each subject will be followed for 30 days for adverse event (AE) monitoring (serious AEs \[SAEs\] will be collected for 90 days after the end of treatment or 30 days after the end of treatment if the subject initiates new anticancer therapy, whichever is earlier).

Conditions

Relapsed Peripheral T-Cell Lymphoma; Refractory Peripheral T-Cell Lymphoma

Keywords

Pembrolizumab; Olaparib; Peripheral T-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rates of treatment with Pembrolizumab plus Olaparib based on Cheson response criteria assessed by independent central review

  The proportion of subjects in the analysis population who have complete response (CR) or partial response (PR).

  Up to 5 years.

Secondary Outcomes (3)

• Overall survival (OS).

  Up to 5 years.

• Progression-free survival (PFS).

  Up to 5 years.

• Safety analysis based on subjects who experienced toxicities as defined by CTCAE criteria..

  Up to 5 years.

Study Arms (1)

Study Treatment

EXPERIMENTAL

Pembrolizumab with Daily Olaparib.

Drug: Pembrolizumab IV infusion Q3W, with daily oral Olaparib.

Interventions

Pembrolizumab IV infusion Q3W, with daily oral Olaparib. DRUG

Pembrolizumab IV infusion 200 mg Q3W, with daily oral Olaparib 300mg BID, over a 3-week cycle.

Study Treatment

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male/female participants who are at least 21 years of age on the day of signing informed consent with histologically or cytologically-confirmed diagnosis of peripheral 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), subcutaneous panniculitis like T-cell lymphoma, and PTCL, not otherwise specified (PTCL-NOS) will be enrolled in this study.
• 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 the time needed to eliminate the study intervention (180 days for Olaparib; no requirement for pembrolizumab) after the last dose of study treatment and refrain from donating sperm during this period.
• 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 the time needed to eliminate the study intervention (180 days for Olaparib; 120 days for pembrolizumab) after the last dose of study treatment.
• Participants must have progressed on treatment with at least one prior systemic anti-cancer therapy including investigational agents. These may include an anti-PD-1/L1 mAb administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria:
• Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
• Has demonstrated disease progression after anti-PD-1/L1 as defined by Cheson response criteria. The initial evidence of PD is to be confirmed by a second assessment no less than 4 weeks from the date of the first documented disease progression, in the absence of rapid clinical progression (as defined in 4.c).
• Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb.
• Progressive disease is determined according to Cheson response criteria.
• This determination is made by the investigator. Once disease progression is confirmed, the initial date of disease progression documentation will be considered the date of disease progression.
• Progression on other systemic anti-cancer therapy including investigational agents is defined by radiographic disease progression based on Cheson response criteria.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have measurable disease based on Cheson criteria. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• 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.
• 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 study intervention.

You may not qualify if:

• 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.
• Has received prior systemic investigational agents within 4 weeks (or shorter interval for kinase inhibitors or other short half-life drugs, per investigator discretion) or has used an investigational device within 4 weeks prior to treatment.
• Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease, with a 1-week washout, is permitted.
• Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
• 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.
• Known additional malignancy that is progressing or has required active treatment within 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 in situ of the bladder that have undergone potentially curative therapy are not excluded.
• 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 intervention.
• 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 except replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid)
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Has a known history of Human Immunodeficiency Virus (HIV) infection.
• 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.
• Has not adequately recovered from major surgery or has ongoing surgical complications.

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead
• Merck Sharp & Dohme LLC: collaborator
• National Medical Research Council (NMRC), Singapore: collaborator

Study Sites (1)

National Cancer Centre, Singapore

Singapore, 168583, Singapore

RECRUITING

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Soon Thye LIM, MBBS, MRCP, Grad Dip (HM)

  National Cancer Centre, Singapore

  STUDY CHAIR

• Jason YS Chan, MBBS, MRCP, MMed, FAMS, PhD

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Soon Thye LIM, MBBS, MRCP, Grad Dip (HM)

CONTACT

+65 64368000; lim.soon.thye@singhealth.com.sg

Jason YS Chan, MBBS, MRCP, MMed, FAMS, PhD

CONTACT

+65 64368000; jason.chan.y.s@singhealth.com.sg

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 29, 2023
• First Posted: December 7, 2023
• Study Start: July 1, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: September 5, 2025

Record last verified: 2025-09

Locations

SG (1)