Pembrolizumab and Olaparib in Homologous-recombination Deficient (HRD) Advanced Colorectal Cancer (CRC).

Sponsor
Grupo Espanol Multidisciplinario del Cancer Digestivo
Study ID
NCT05201612
Phase
PHASE2
Status
Unknown

Conditions

  • Metastatic Colorectal Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Olaparib — DRUG
    Olaparib 300 mg, orally (po), twice a day (BID) continuously
  • Pembrolizumab — DRUG
    Pembrolizumab 200 mg, intravenously (IV), every 21 days. Max 2 years (i.e. 35 cycles)

Study Details

Colorectal Cancer (CRC) is a leading cause of cancer-related death. Around 30% of patients present with advanced disease and 50% of those that attempt curative surgery will eventually relapse. The potential synergism of combining PARP inhibitor and PD-L1 is based on the hypothesis that pharmacological inhibition of PARP by olaparib will result in enhanced immunogenicity which can be further enhanced with an immune checkpoint inhibitor such as pembrolizumab. This may occur through a number of mechanisms, such as increased production of cytokines and chemokines that have the potential to promote antitumour immunity, upregulation of surface receptors which render tumour cells more visible to detection by cytotoxic T cells thereby leading to death of tumour cells and release of neoantigens, that help promote antigen presentation and immune priming. This hypothesis is supported by preclinical studies in mouse models of cancer, demonstrating that administration of a PARP inhibitor to sensitive tumour types resulted in increased T cell infiltration and immune activation within tumours. The primary hypothesis is that Olaparib and pembrolizumab combination will lead to an increase in objective response rate in patients with refractory metastatic colorectal cancer (mCRC) with DNA homologous-recombination-repair deficiency (HRD) from 1.5% in benchmark studies to up to \>10%. The primary objective of the study is to determine the objective response rate (ORR) of pembrolizumab in combination with olaparib, assessed by the investigator per RECIST criteria version 1.1. Secondary objectives include efficacy in terms of disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and duration of response (DOR); safety and an exploratory study of biomarkers associated with treatment efficacy and disease prognosis.

Key Dates

Start date
Jul 7, 2022
Status verified
Feb 2023
Primary completion
Sep 30, 2024
Completion
Mar 31, 2025

Study Design

Enrollment
40 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Pembrolizumab plus olaparib
    Treatment cycles will be 21 days in length. All participants will receive treatment as follows: Olaparib 300 mg, orally (po), twice a day (BID) continuously. Pembrolizumab 200 mg, intravenously (IV), every 21 days. Treatment will be continued in the absence of disease progression, unacceptable toxicity, withdrawal of consent or death. Pembrolizumab will be administered up to a maximum of 2 years (35 cycles).

Primary Outcome Measure

Objective response rate (ORR) [ Time Frame: Throughout the study period, approximately 10 months per patient from first study dose. ]

Central Contacts

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