Aims:
We report an interim analysis from an open-label phase (Ph) 1b/2 study evaluating the safety and efficacy of ERI in combination with PEM in patients (pts) with pretreated mTNBC.
Methods:
At data cutoff (7/12/16), 89 pts with mTNBC (age ≥18 yrs, ECOG PS 0-1, ≤2 prior lines of chemotherapy for metastatic disease) were enrolled. Ph1b included a safety cohort of ≥6 pts who received intravenous (IV) ERI 1.4mg/m2 on days (d) 1/8 and IV PEM 200mg on d1 of a 21-d cycle. Dose-limiting toxicity (DLT) of the combination was assessed in the first cycle to determine the recommended Ph2 dose (RP2D). In Ph2, pts were stratified based on prior chemotherapy in the metastatic setting (0 vs 1–2 prior lines). Primary endpoints: safety and tolerability (Ph1b), objective response rate (ORR; Ph2). Secondary endpoints included progression-free survival, overall survival, and duration of response.
Results:
39 pts were assessed (n=7, phase 1b; n=32, phase 2). No DLTs were observed. The RP2D was defined as ERI 1.4mg/m2 on d1/d8 and PEM 200mg on d1 of a 21-d cycle. The most common adverse events (AEs; all grades) were fatigue (74%), nausea (51%), peripheral neuropathy (44%), and neutropenia (39%). The most common AEs of grade (G) 3 or 4 were neutropenia (31%) and fatigue (8%). 69% of pts had AEs leading to dose adjustment. There was 1 G5 event (respiratory failure, not treatment related). Overall, ORR was 33%. ORR was higher in pts with no prior chemotherapy in the metastatic setting compared to pts treated with 1-2 prior lines in the metastatic setting (41% vs 27%, respectively) and was similar between PD-L1 positive and negative cohorts (29% vs 33%, respectively).
Conclusions:
ERI plus PEM demonstrated activity in pts with mTNBC. AEs observed with the combination were comparable to those observed with either as monotherapy.