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

Phase 1

Recruiting

• Conditions: Advanced Solid Tumor
• Interventions: Drug: RP-3467 at assigned dose and schedule; Drug: Olaparib 200-300 mg BID, daily

• Registration Number: NCT06560632
• Lead Sponsor: Repare Therapeutics

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

Study Timeline

• Study First Submitted: 2024-08-09
• Study First Submitted QC: 2024-08-16
• Study First Posted: 2024-08-19
• Study Start: 2024-09-17
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-14
• Last Update Posted: 2024-11-18
• Primary Completion: 2026-10
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 52

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm2: RP-3467 + Olaparib combination	Olaparib 200-300 mg BID, daily	Eligible participants will be treated with escalating doses of RP-3467 in combination with Olaparib
Arm 1: RP-3467 monotherapy	RP-3467 at assigned dose and schedule	Eligible participants will be treated with escalating doses of RP-3467 monotherapy
Arm2: RP-3467 + Olaparib combination	RP-3467 at assigned dose and schedule	Eligible participants will be treated with escalating doses of RP-3467 in combination with Olaparib

Primary Outcome Measures

Name	Time	Method
To assess the safety and tolerability of RP-3467 alone and in combination with olaparib	20 months	Incidence and severity of treatment-emergent adverse events (TEAEs) as assessed per NCI CTCAE v5.0 criteria
To define a preliminary recommended Phase 2 dose (RP2D) of RP-3467 in combination with olaparib	24 months

Secondary Outcome Measures

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

Trial Locations

Locations (4)

Participating Site #1025; 🇺🇸 San Francisco, California, United States

Participating Site # 1008; 🇺🇸 New York, New York, United States

Participating Site # 1004; 🇺🇸 New York, New York, United States

Participating Site # 1001; 🇺🇸 Houston, Texas, United States