Study of RP-3500 (Camonsertib) With Niraparib or Olaparib in Advanced Solid Tumors

Phase 1b/2 Study of ATR InhibiTor RP-3500 and PARP Inhibitor Combinations in Patients With Molecularly Selected Cancers (ATTACC)

The primary purpose of this study is to assess the safety and tolerability of niraparib or olaparib in combination with RP-3500 (camonsertib), in patients with eligible advanced solid tumors, determine the maximum tolerated dose (MTD) of RP-3500 (camonsertib) in combination with niraparib or olaparib, examine pharmacokinetics (PK) and assess anti-tumor activity.

This is a first-in-human Phase 1b/2, multi-center, open-label, dose-escalation and expansion study to:

• Evaluate the safety profile and MTD of RP-3500 (camonsertib) when administered orally in combination with niraparib or olaparib to establish the recommended Phase 2 dose and schedule.
• Characterize the PK profile of RP-3500 (camonsertib) in combination with niraparib or olaparib
• Assess anti-tumor activity associated with RP-3500 (camonsertib) in combination with niraparib or olaparib
• Examine biomarker responses and establish a correlation with RP-3500 (camonsertib) treatment in combination with niraparib or olaparib.

After the RP2D and schedule is determined, expansion cohort(s) for RP-3500 (camonsertib) in combination with niraparib or olaparib will be enrolled to study the anti-tumor effect, and further examine the safety, PK, and pharmacodynamic (PD).

Sponsor decided to terminate study early therefore, the Phase 2 expansion was not conducted

Inclusion Criteria:

• Male or female and ≥18 years-of-age at the time of signature of the informed consent
• Confirmed advanced solid tumors resistant or refractory to standard treatment
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
• Evaluable disease as per RECIST v1.1
• Next generation sequencing (NGS) report obtained in CLIA-certified or equivalent laboratory demonstrating eligible tumor biomarkers.
• Submission of available tumor tissue or willingness to have a biopsy performed if safe and feasible
• Acceptable hematologic and organ function at screening
• Negative pregnancy test for women of childbearing potential at Screening and prior to first study drug.
• Ability to swallow and retain oral medications.

Exclusion Criteria:

• Prior therapy with an ATR or DNA-dependent protein kinase (DNA-PK) inhibitor.
• Chemotherapy, small molecule anticancer or biologic anticancer therapy given within 10 days or 5 half-lives (whichever is longer), prior to first dose of study drug.
• Use of radiotherapy (except for palliative reasons) within 7 days prior to first dose of study drug.
• 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.
• No other anticancer therapy is to be permitted while the patient is receiving study treatment.
• Major surgery ≤28 days or minor surgical procedures ≤7 days prior to first study treatment dose.
• Uncontrolled, symptomatic brain metastases.
• Uncontrolled high blood pressure
• History of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) diagnosis
• Presence of other known active invasive cancers.
• Pregnant or breastfeeding women.
• Psychological, familial, sociological, or geographical conditions that do not permit compliance with the study protocol and/or follow-up procedures outlined in the protocol.