Pembrolizumab and Olaparib in Homologous-recombination Deficient (HRD) Advanced Colorectal Cancer (CRC).
Status:
Not yet recruiting
Trial end date:
2024-12-01
Target enrollment:
Participant gender:
Summary
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.
Phase:
Phase 2
Details
Lead Sponsor:
Grupo Espanol Multidisciplinario del Cancer Digestivo