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

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.

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

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