NCT05033756

Comprehensive Analysis of Predictors of the Treatment With Pembrolizumab and Olaparib in Patients With Unresectable or Metastatic HER2 Negative Breast Cancer and a Deleterious Germline Mutation or a Homologous Recombination Deficiency (COMPRENDO

A Phase II Open-Label Study for the Comprehensive Analysis of Predictors of the Treatment With Pembrolizumab and Olaparib in Patients With Unresectable or Metastatic HER2 Negative Breast Cancer and a Deleterious Germline Mutation in BRCA1/2, ATM, BARD1, CHEK2, FANCC, PALB2, RAD51C, RAD51D, SLX4, XRCC2 or a Homologous Recombination Deficiency

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 11 (actual)
• Sponsor: Institut fuer Frauengesundheit · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study will examine the combination of pembrolizumab and olaparib in three populations. * Cohort 1: aBC patients with a germline mutation in BRCA1 or BRCA2, * cohort 2: aBC patients with a germline mutation in one of the moderate penetrance homologous repair genes (ATM, BARD1, CHEK2, FANCC, PALB2, RAD51C, RAD51D, SLX4, XRCC2), and * cohort 3: aBC patients with a HRD as assessed by whole genome sequencing.

Detailed description

This is a multicenter, prospective, phase II, one-arm, three-cohort, open-label study of pembrolizumab in combination with olaparib in patients with advanced HER2 negative breast cancer who have either * a deleterious germline mutation in BRCA1/2 irrespective of tumor HRD status (Cohort 1), * or a deleterious germline mutation in ATM, BARD1, CHEK2, FANCC, PALB2, RAD51C, RAD51D, SLX4, XRCC2 irrespective of tumor HRD status (Cohort 2), * or a centrally confirmed high tumor HRD status, but no deleterious germline mutation in BRCA1/2, ATM, BARD1, CHEK2, FANCC, PALB2, RAD51C, RAD51D, SLX4, XRCC2 (Cohort 3). HRD assessment needs to be performed on a tumor biopsy not more than 12 months before study entry. All eligible participants according to the definition of cohorts 1-3 will receive pembrolizumab i.v. 200 mg q3w in combination with olaparib tablets 300 mg twice daily (total dose 600 mg per day). Study medication will be withdrawn/ended in case of onset of unacceptable toxicities, progression, withdrawal of consent, death, or end of study, whichever occurs first. Safety follow-up is planned for 90 days after the last application of study medication. Participants will be followed for survival for a maximum of 18 months after therapy start.

Conditions

• Malignant Neoplasm of Breast
• Breast Cancer

Interventions

Type	Name	Description
DRUG	Pembrolizumab Injection [Keytruda]	The planned dose of pembrolizumab for this study is 200 mg every 3 weeks (Q3W). Based on the totality of data generated in the Keytruda development program, 200 mg Q3W is the appropriate dose of pembrolizumab for adults across all indications and regardless of tumor type.
DRUG	Olaparib Oral Tablet [Lynparza]	All patients will receive olaparib treatment as an addition to pembrolizumab. The dose of olaparib used in this study is 300 mg twice daily (total daily dose of 600 mg) which is the currently approved dose.

Timeline

• Start date: 2022-07-30
• Primary completion: 2025-01-01
• Completion: 2026-02-01
• First posted: 2021-09-05
• Last updated: 2024-05-07

Locations

6 sites across 1 country: Germany

Regulatory

• FDA-regulated drug study