Clinical trial NCT06560632: Phase 1 Trial of RP-3467 Alone and in Combination With Olaparib in Participants With Advanced Solid Tumors
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: Repare Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-08-19
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: To assess the safety and tolerability of RP-3467 alone and in combination with olaparib
timeFrame: 20 months
measure: To define a preliminary recommended Phase 2 dose (RP2D) of RP-3467 in combination with olaparib
timeFrame: 24 months
Secondary outcomes:
measure: To assess PK parameters of RP-3467 alone or in combination with olaparib with calculation of maximum observed plasma concentration (Cmax)
timeFrame: 19 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: # 1025, The University of California
state: California
city: Saint Louis
country: United States
facility: # 1011, The Washington University
state: Missouri
city: New York
country: United States
facility: # 1008, Columbia University
state: New York
city: New York
country: United States
facility: # 1004, Memorial Sloan-Kettering Cancer Center
state: New York
city: Houston
country: United States
facility: # 1001, The University of Texas M.D. Anderson Cancer Center
state: Texas
Study officials:
References: