Dose escalation, DLTs and MTD
Toxicities, DLTs, neutropenia, toxicity, toxicities, vomiting, dehydration, pyrexia, sepsis
DEHYDRATION, SEPSIS, ADVERSE EVENTS, NEUTROPENIA
In the A1 cohort, 16 patients were enroled and completed final (week 12) visit. No DLTs were reported in cohort A1. The TiTE-CRM recommended dose escalation for each dose level until the maximum level. Berzosertib 240 mg/m2 twice weekly (schedule 6) was identified as the RP2D in this combination.In the A2 cohort, 18 patients started treatment, with two patients experiencing DLT; grade 3 neutropenia and grade 3 pyrexia in the first patient and sepsis, vomiting and dehydration (all grade 3) in the second patient. Both patients who experienced DLT received berzosertib at 140 mg/m² once a week (schedule 3). Although no dose-limiting toxicities (DLTs) were recorded according to the study protocol with 140 mg/m² twice a week (schedule 4), some patients experienced toxicities that nearly met the definition of DLTs, such as toxicity that resulted in the missed administration of two consecutive doses of berzosertib across cycles. DLTs observed in both cohort A1 and A2 are presented in Table Dose Limiting Toxicities observed in cohort A1 and A2.Number of participants included in the primary safety analysis and 12-week overall RECIST efficacy reporting for both stages are included in the a: Five most common system organ classes to experience adverse events by grade in A1. b: Five most common system organ classes to experience adverse events by grade in A2.Berzosertib 140 mg/m