Trial Outcomes & Findings for RP-3500 and Olaparib in DNA Damage Repair Pathway Deficient Relapsed/Refractory Chronic Lymphocytic Leukemia (NCT NCT05405309)

RP-3500 and Olaparib in DNA Damage Repair Pathway Deficient Relapsed/Refractory Chronic Lymphocytic Leukemia

This outcome will report the number of patients who experienced a Dose-Limiting Toxicity (DLT) in Phase Ib Dose Level 1, Phase Ib Dose Level 2, Phase Ib Dose Level 3, and Phase Ib Dose Level -1 during the DLT window (Cycle 1 Day 1 to Cycle 1 Day 21). A keyboard phase I design was employed; the target toxicity was 30% with an equivalence interval between 25-33% of patients. The first 5 patients were treated at DL-1 (camonsertib 40mg daily and olaparib 100mg BID dosing 3 days per week).

This outcome will assess the overall responseof combination RP-3500 and olaparib. Overall response is defined by the count of subjects achieving any confirmed partial (PR) and complete response (CR) as assessed by 2018 International Working Group on Chronic Lymphocytic Leukemia (iwCLL) response criteria. Subjects without a baseline/screening tumor assessment or at least one on-treatment assessment will be considered non-responders.

This outcome measure will assess the safety and tolerability of RP-3500 and olaparib. The severity of AEs was assessed using CTCAE v5.0 criteria, a 1-5 scale with higher numbers indicating greater severity. Grade 1 indicates "mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated" and Grade 5 indicates "death related to AE". The severity of adverse hematologic adverse events was assessed using the 2018 IWCLL grading scale. Grade 0 indicates "≤10% decrease in platelets (PLT) or hemoglobin (Hb) from baseline and ≥2 absolute neutrophil count (ANC)" and Grade 4 indicates "≥75% decrease in PLT or Hb from baseline and \<0.5 ANC" This outcome measure will report the count of participants who experienced each AE grade. Subjects were monitored for adverse events from the start of treatment until 28 days after the last dose of the study drug.

Progression-free survival (PFS) as defined as the time from study drug initiation to the time documented disease progression (as assessed by 2018 iwCLL criteria) or death from any cause. Patients were followed for PFS until progression of disease was noted or death, whichever occurred first. This outcome will report the median PFS with 95% confidence intervals.

This outcome will assess OS as defined as the time between treatment initiation and death of any cause. Subjects were followed for OS from the initiation of therapy until death from any cause or until the study was terminated. Subjects lost to follow-up or refused follow-up were censored at the time of the last known follow-up. This outcome will report the median OS with 95% confidence intervals.

DoR is defined as the interval of time from the date of the initial documented response (PR or better as per 2018 iwCLL criteria for response) to the time of progression. Patients would be followed for DoR from the date of the initial documented response until progression of disease was noted or death, whichever occurred first. This outcome would have reported the median DoR with 95% confidence intervals.