Study of RP-3500 (Camonsertib) With Niraparib or Olaparib in Advanced Solid Tumors

NCT ID: NCT04972110

Last Updated: 2025-10-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 156 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-21
• Study Completion Date: 2024-11-13

Brief Summary

The primary purpose of this study is to assess the safety and tolerability of niraparib or olaparib in combination with RP-3500 (camonsertib), in patients with eligible advanced solid tumors, determine the maximum tolerated dose (MTD) of RP-3500 (camonsertib) in combination with niraparib or olaparib, examine pharmacokinetics (PK) and assess anti-tumor activity.

Detailed Description

This is a first-in-human Phase 1b/2, multi-center, open-label, dose-escalation and expansion study to:

• Evaluate the safety profile and MTD of RP-3500 (camonsertib) when administered orally in combination with niraparib or olaparib to establish the recommended Phase 2 dose and schedule.
• Characterize the PK profile of RP-3500 (camonsertib) in combination with niraparib or olaparib
• Assess anti-tumor activity associated with RP-3500 (camonsertib) in combination with niraparib or olaparib
• Examine biomarker responses and establish a correlation with RP-3500 (camonsertib) treatment in combination with niraparib or olaparib.

After the RP2D and schedule is determined, expansion cohort(s) for RP-3500 (camonsertib) in combination with niraparib or olaparib will be enrolled to study the anti-tumor effect, and further examine the safety, PK, and pharmacodynamic (PD).

Sponsor decided to terminate study early therefore, the Phase 2 expansion was not conducted

Conditions

Advanced Solid Tumor, Adult

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase Ib Dose Escalation

Multiple dose levels of RP-3500 (camonsertib) for oral administration in combination with niraparib and/or Multiple dose levels of RP-3500 (camonsertib) for oral administration in combination with olaparib

Group Type: EXPERIMENTAL

RP-3500 (camonsertib)

Intervention Type: DRUG

RP-3500 (camonsertib, ATR inhibitor) in combination with niraparib or olaparib (PARP inhibitors)

Phase 2 Expansion Cohorts

Expansion cohort with RP-3500 (camonsertib) + niraparib and/or Expansion cohort RP-3500 (camonsertib) + olaparib

Group Type: EXPERIMENTAL

RP-3500 (camonsertib)

Intervention Type: DRUG

RP-3500 (camonsertib, ATR inhibitor) in combination with niraparib or olaparib (PARP inhibitors)

Interventions

RP-3500 (camonsertib)

RP-3500 (camonsertib, ATR inhibitor) in combination with niraparib or olaparib (PARP inhibitors)

Intervention Type: DRUG

Other Intervention Names

niraparib; olaparib

Eligibility Criteria

Inclusion Criteria

• Male or female and ≥18 years-of-age at the time of signature of the informed consent
• Confirmed advanced solid tumors resistant or refractory to standard treatment
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
• Evaluable disease as per RECIST v1.1
• Next generation sequencing (NGS) report obtained in CLIA-certified or equivalent laboratory demonstrating eligible tumor biomarkers.
• Submission of available tumor tissue or willingness to have a biopsy performed if safe and feasible
• Acceptable hematologic and organ function at screening
• Negative pregnancy test for women of childbearing potential at Screening and prior to first study drug.
• Ability to swallow and retain oral medications.

Exclusion Criteria

• Prior therapy with an ATR or DNA-dependent protein kinase (DNA-PK) inhibitor.
• Chemotherapy, small molecule anticancer or biologic anticancer therapy given within 10 days or 5 half-lives (whichever is longer), prior to first dose of study drug.
• Use of radiotherapy (except for palliative reasons) within 7 days prior to first dose of study drug.
• History or current condition, therapy, or laboratory abnormality that might confound the study results, or interfere with the patient's participation for the full duration of the study treatment.
• No other anticancer therapy is to be permitted while the patient is receiving study treatment.
• Major surgery ≤28 days or minor surgical procedures ≤7 days prior to first study treatment dose.
• Uncontrolled, symptomatic brain metastases.
• Uncontrolled high blood pressure
• History of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) diagnosis
• Presence of other known active invasive cancers.
• Pregnant or breastfeeding women.
• Psychological, familial, sociological, or geographical conditions that do not permit compliance with the study protocol and/or follow-up procedures outlined in the protocol.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Repare Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Participating Site #1018

Phoenix, Arizona, United States

Participating Site #1025

San Francisco, California, United States

Participating Site #1028

Aurora, Colorado, United States

Participating Site #1012

New Haven, Connecticut, United States

Participating Site #1017

Jacksonville, Florida, United States

Participating Site #1009

Baltimore, Maryland, United States

Participating Site #1015

Ann Arbor, Michigan, United States

Participating Site # 1016

Rochester, Minnesota, United States

Participating Site #1026

New York, New York, United States

Participating Site # 1008

New York, New York, United States

Participating Site #1029

Eugene, Oregon, United States

Participating Site # 1001

Houston, Texas, United States

Participating Site # 1013

Salt Lake City, Utah, United States

Countries

United States

References

Silverman IM, Schonhoft JD, Herzberg B, Yablonovitch A, Lagow E, Fiaux PC, Safabakhsh P, Sethuraman S, Ulanet D, Yang J, Kim I, Basciano P, Cecchini M, Lee E, Lheureux S, Fontana E, Carneiro BA, Reis-Filho JS, Yap TA, Zinda M, Rosen EY, Rimkunas V. Genomic and Epigenomic ctDNA Profiling in Liquid Biopsies from Heavily Pretreated Patients with DNA Damage Response-Deficient Tumors. Clin Cancer Res. 2025 Oct 1;31(19):4136-4149. doi: 10.1158/1078-0432.CCR-25-1248.

Reference Type: DERIVED

PMID: 40705098 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

RP-3500-03

Identifier Type: -

Identifier Source: org_study_id