MedTrace Logo

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

NCT05201612 · Status: UNKNOWN · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 40

Last updated 2023-02-24

No results posted yet for this study

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.

Conditions

Interventions

DRUG

Olaparib

Olaparib 300 mg, orally (po), twice a day (BID) continuously

DRUG

Pembrolizumab

Pembrolizumab 200 mg, intravenously (IV), every 21 days. Max 2 years (i.e. 35 cycles)

Sponsors & Collaborators

  • Merk Sharp & Dohme España S.A.

    collaborator UNKNOWN

  • Grupo Espanol Multidisciplinario del Cancer Digestivo

    lead OTHER

Principal Investigators

  • Rocío García Carbonero, M.D.; Ph.D. · Hospital Universitario 12 de Octubre

  • María del Carmen Riesco Martinez, M.D.; Ph.D. · Hospital Universitario 12 de Octubre

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2022-07-07
Primary Completion
2024-09-30
Completion
2025-03-31

Countries

  • Spain

Study Locations

More Related Trials

Entities

Drugs
Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05201612 on ClinicalTrials.gov