Study design and treatment
toxicity, toxicities, tumor, PK/PD
TUMOR
TRESR (Patients were treated with single-agent camonsertib at doses ranging from 5–160 mg QD to 40–80 mg twice daily, administered orally on a 5/2 or 3/4 weekly schedule. An intermittent schedule of 2 weeks on/1 week off was also evaluated at dose levels of 160 mg and 200 mg QD (3/4). Each cycle comprised 21 d of treatment. Module 1 dose-escalation decisions based on patients in M1a and M1b cohorts were governed by the Bayesian optimal interval (BOIN) design starting with single-patient cohorts in M1a. Evidence of pharmacologic activity—defined as grade ≥2 drug-related toxicity at any cycle, PK data demonstrating exposure levels predicted to be efficacious based on non-clinical studies or other evidence of treatment-related activity—served as the trigger for cohort expansion and opening of M1b. Escalation of M1a and M1b occurred in parallel until the maximum tolerated dose (MTD) of RP2D was determined for each schedule. Backfill cohorts were employed to (1) aid in the assessment of possible anti-tumor activity in a subset of patients with a specific gene abnormality or tumor type; (2) allow additional PK/PD evaluation; and (3) further assess drug-related toxicities. Patient safety review and dose decisions were carried out by a Safety Review Committee, comprised of the study investigators and sponsor representatives.