Fig. 1: Study flow diagram for Parts A and B.
During Part A, patients were enrolled into a dose escalation phase of amcenestrant monotherapy from 20-600 mg once daily. During Part B, patients were enrolled into a dose-expansion phase at the RP2D determined in Part A. aThe first patient treated at each new DL will be followed for a minimum of 1 week prior to enrolling and treating two additional patients. If none of the three patients experience a DLT, the next cohort starts one DL higher. If one of the three patients experiences a DLT, up to three additional patients are treated at this DL. If two or more patients experience a DLT, the maximum administered dose is reached. bDL2bis is investigated if at least one patient at DL1 shows ≤ 30% inhibition of the target by 18F-FES PET or all patients treated at DL2 have >85% inhibition of the target by 18F-FES PET. DL dose level, DLT dose-limiting toxicity, ER+ estrogen receptor positive, 18F-FES PET 18F-fluoroestradiol positron emission tomography, HER2− human epidermal growth factor receptor 2-negative, MTD maximum tolerated dose, RP2D recommended Phase 2 dose, PK pharmacokinetics, QD once daily.
