The primary purpose of this study is to define the maximum tolerated dose (MTD) and determine a recommended Phase 2 dose (RP2D) and schedule of orally-administered RP-3500 (camonsertib) alone or in combination with talazoparib, a PARP inhibitor, or Gemcitabine in patients with advanced solid tumors with ATR inhibitor-sensitizing mutations. This study will also evaluate the safety and tolerability of RP-3500 (camonsertib) alone or in combination with talazoparib or gemcitabine, examine both the pharmacokinetics (PK)and pharmacodynamics (PD)and investigate its anti-tumor activity in solid tumors.
This is a first-in-human, Phase 1/2a, multi-center, open-label, dose-escalation and expansion study to: * Evaluate the safety profile and MTD of RP-3500 (camonsertib) when administered orally, alone and in combination with talazoparib or gemcitabine, to establish the dose and schedule recommended for the Phase 2 * Characterize the PK profile of RP-3500 (camonsertib) alone or in combination with talazoparib or gemcitabine * Identify anti-tumor activity associated with RP-3500 (camonsertib) given alone or in combination with talazoparib or gemcitabine The initial cohorts will test RP-3500 (camonsertib) as monotherapy. Additional cohorts will enroll with RP-3500 (camonsertib) in combination with talazoparib or gemcitabine. After the RP2D and schedule is determined, expansion cohort(s) for RP-3500 (camonsertib) will be enrolled to study the anti-tumor effect, and further examine the safety and PK of RP-3500 (camonsertib) at the RP2D
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
276
#1014, Northwestern University
Chicago, Illinois, United States
#1006, Massachusetts General Hospital
Boston, Massachusetts, United States
#1002, Dana Farber Cancer Institute
Frequency of Treatment-Related Adverse Event of CTCAE Grade 3 and Above
Treatment-emergent adverse events (TEAEs) are those events that occur or worsen on or after the first dose of study drug up through 30 days post the last dose (or cross over to a different module) or the start of subsequent anticancer therapy. AEs are considered related to treatment if the relationship to camonsertib or the other combination drug (in the study regimen) is "Related" (include unknown relationship) as indicated on the AE eCRF page based on investigator's assessment.
Time frame: Start of treatment to 30 days post last dose, up to 1 year
Frequency of Dose Limiting Toxicity (DLT)
Toxicity were assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. A toxicity was considered dose-limiting if it occurred during the first cycle and was deemed at least possibly related to study treatment. If multiple toxicities occurred, the most severe toxicity was used in the assessment. The DLT Evaluable population consists of patients who received at least 80% of planned total doses of camonsertib , 80% of planned total doses of camonsertib and talazoparib, or 80% of planned total doses of camonsertib and 100% of gemcitabine; complete all required safety evaluations and are observed through the end of Cycle 1; or patients who experience a DLT qualifying event in the first cycle of treatment.
Time frame: Either 21 days or 28 days (1 cycle) from the initiation of the study treatment.
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Boston, Massachusetts, United States
#1004, Memorial Sloan Kettering Cancer Institute
New York, New York, United States
#1005, Duke Cancer Institute
Durham, North Carolina, United States
#1007, Rhode Island Hospital
Providence, Rhode Island, United States
#1003, Sarah Cannon Research Institute
Nashville, Tennessee, United States
#1001, The University of Texas M.D. Anderson Cancer Center
Houston, Texas, United States
#2001, Princess Margaret Cancer Centre
Toronto, Ontario, Canada
#4001, Copenhagen University Hospital Rigshospitalet - Blegdamsvej
Copenhagen, DK, Denmark
...and 3 more locations