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

Phase 1 Trial of the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Clinical Activity of RP-3467 Alone and in Combination With Olaparib in Participants With Advanced Solid Tumors (POLAR Trial)

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.

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: RP-3467 at assigned dose and schedule; Drug: Olaparib 200-300 mg BID, daily

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

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • # 1025, The University of California
  • Missouri
    • St Louis, Missouri, United States, 63130
      • # 1011, The Washington University
  • New York
    • New York, New York, United States, 10032
      • # 1008, Columbia University
    • New York, New York, United States, 10065
      • # 1004, Memorial Sloan-Kettering Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • # 1001, The University of Texas M.D. Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: RP-3467 monotherapy; Eligible participants will be treated with escalating doses of RP-3467 monotherapy	Drug: RP-3467 at assigned dose and schedule; Eligible participants will be treated with escalating doses of RP-3467 monotherapy
Experimental: Arm2: RP-3467 + Olaparib combination; Eligible participants will be treated with escalating doses of RP-3467 in combination with Olaparib	Drug: RP-3467 at assigned dose and schedule; Eligible participants will be treated with escalating doses of RP-3467 monotherapy; Drug: Olaparib 200-300 mg BID, daily; Eligible participants will be treated with escalating doses of RP-3467 in combination with Olaparib; Other Names: Lynparza; RP-3467 at assigned dose and schedule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Participants Who Experienced Dose-limiting Toxicities (DLT) During the Study Treatment	The assessment of DLTs was conducted to evaluate the safety and tolerability of RP-3467 administered as monotherapy and in combination with olaparib in participants with advanced solid tumors.	Start of treatment to 30 days post last dose, up to 13 months

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess PK parameters of RP-3467 alone or in combination with olaparib with calculation of maximum observed plasma concentration (Cmax)	19 months

Collaborators and Investigators

• Sponsor: Repare Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2024
• Primary Completion (Actual): October 28, 2025
• Study Completion (Actual): October 28, 2025

Study Registration Dates

• First Submitted: August 9, 2024
• First Submitted That Met QC Criteria: August 16, 2024
• First Posted (Actual): August 19, 2024

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: December 24, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Organization and Administration; Health Services Administration; olaparib; BID protein, human; Appointments and Schedules
• Other Study ID Numbers: RP-3467-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No