Phase 1 Trial of RP-3467 Alone and in Combination With Olaparib in Participants With Advanced Solid Tumors

NCT ID: NCT06560632

Last Updated: 2026-01-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-17
• Study Completion Date: 2025-10-28

Brief Summary

This is a multicenter, open-label Phase 1 trial to investigate the safety, PK, and pharmacodynamics of the Polθ inhibitor RP-3467 alone or in combination with the poly-ADP ribose polymerase inhibitor (PARPi) olaparib in adults with molecularly selected advanced solid tumors.

Detailed Description

This is a first-in-human Phase 1, multi-center, open-label, dose-escalation study to:

• Evaluate the safety profile of RP-3467 when administered orally alone and in combination with olaparib and to define the MTD or MAD for RP-3467 monotherapy and the RP2D for the combination
• Characterize the PK profile of RP-3467 alone and in combination with olaparib

Conditions

Advanced Solid Tumor

Study Design

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

Study Groups

Arm 1: RP-3467 monotherapy

Eligible participants will be treated with escalating doses of RP-3467 monotherapy

Group Type: EXPERIMENTAL

RP-3467 at assigned dose and schedule

Intervention Type: DRUG

Eligible participants will be treated with escalating doses of RP-3467 monotherapy

Arm2: RP-3467 + Olaparib combination

Eligible participants will be treated with escalating doses of RP-3467 in combination with Olaparib

Group Type: EXPERIMENTAL

RP-3467 at assigned dose and schedule

Intervention Type: DRUG

Eligible participants will be treated with escalating doses of RP-3467 monotherapy

Olaparib 200-300 mg BID, daily

Intervention Type: DRUG

Eligible participants will be treated with escalating doses of RP-3467 in combination with Olaparib

Interventions

RP-3467 at assigned dose and schedule

Eligible participants will be treated with escalating doses of RP-3467 monotherapy

Intervention Type: DRUG

Olaparib 200-300 mg BID, daily

Eligible participants will be treated with escalating doses of RP-3467 in combination with Olaparib

Intervention Type: DRUG

Other Intervention Names

RP-3467 at assigned dose and schedule; Lynparza

Eligibility Criteria

Inclusion Criteria

• Male or female participants ≥18 years of age at the time of signing the informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Participant must have one of the following that has progressed or was non-responsive to prior systemic therapy and for which no standard or available known therapeutic option exists:

1. locally advanced or metastatic epithelial ovarian cancer (including fallopian tube or primary peritoneal), or

2. metastatic breast cancer, or

3. metastatic castration-resistant prostate cancer (mCRPC), or

4. pancreatic adenocarcinoma

• Measurable disease per RECIST v1.1 (exceptions for participants with non-measurable but evaluable disease [per RECIST and or PSA/CA-125])
• Next generation sequencing (NGS) report demonstrating eligible tumor biomarker
• Provision of archival tumor tissue, or if adequate archival tumor tissue is not available, provision of a fresh biopsy if there is a lesion that can be safely biopsied
• Acceptable organ function at Screening
• Acceptable hematologic function at Screening
• Life expectancy ≥12 weeks after the start of the treatment according to the Investigator's judgment

Exclusion Criteria

• 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.
• Uncontrolled, symptomatic brain metastases.
• Presence of other known active invasive cancers
• History of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) diagnosis
• Prior therapy with a Polθ inhibitor other than RP-3467

• 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

# 1025, The University of California

San Francisco, California, United States

# 1011, The Washington University

St Louis, Missouri, United States

# 1008, Columbia University

New York, New York, United States

# 1004, Memorial Sloan-Kettering Cancer Center

New York, New York, United States

# 1001, The University of Texas M.D. Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

RP-3467-01

Identifier Type: -

Identifier Source: org_study_id