This trial is based on a combination strategy with two immunostimulatory agents in the search of synergism that may induce responses with long term clinical benefit in ABC pts. Here, we report the results from the run-in-phase of the study (ClinicalTrials.gov Identifier: NCT03025880).
HER2-negative ABC pts previously treated with anthracyclines and taxanes (unless contraindicated) and ≥ 2 lines of hormone therapy, if hormone receptor (HR)-positive disease, were eligible. Treatment consisted of 21-day cycles (cy) of P 200mg on day 1 and Gem on days 1 and 8. A 6 + 6 design was used with 2 dose levels (DL) of Gem: 1250mg/m2 (DL0) and 1000mg/m2 (DL1). The primary objective was to define the Recommended Phase II Dose (RP2D) based on dose limiting toxicities (DLT) during the first cy (<33% of pts with a DLT); secondary objectives included evaluation of safety and efficacy. Pts were treated until progression, or unacceptable toxicity whatever occurs first.
Fourteen pts were included in DL0; 3 pts were replaced due to early progressive disease (PD). DL1 was not explored as DL0 was considered the RP2D . Median age was 48 years (range 32-61), and 9 pts had triple negative disease. The majority of pts had an ECOG performance status ≤ 1 (n = 13) and visceral involvement (n = 12); 8 pts had ≤2 involved sites. Median number of prior lines (any therapy) for metastatic disease was 3 (range 1-7). Pts received a median of 4.5 cy of Gem (range 1-11) and 3 cy of P (range 1-11). One DLT was observed, Gem dose omission on day 8 due to grade (G) 2 thrombocytopenia. G ≥ 3 adverse events (AEs) related to the treatment were reported on 5 pts; G4 AEs included thrombocytopenia and lymphopenia (7.1% each); G3 AEs included neutropenia (14.3%), anemia, leukopenia, thrombocytopenia, diarrhea and transaminases increase (7.1% each). The best overall tumor response was stable disease on 3 pts at the time of this analysis; 9 pts discontinued treatment due to PD, 1 pt due to respiratory failure, and 2 pts died of breast cancer. Twenty-two pts have been included on the ongoing phase II part.
P can be safely combined with Gem. P 200mg and Gem 1250mg/m2 was declared as the RP2D.
NCT03025880.
GEICAM, Spanish Breast Cancer Group.
Merck Sharp & Dohme Corp (MSD).
J. Cortes Castan: Honoraria: Roche, Novartis, Eisai, Celgene, Pfizer. Consulting/advisor: Roche, Celgene, AstraZeneca, Cellestia Biotech, Biothera, Merus, Seattle Genetics. E.M. Carrasco: Husband: Honoraria: Pfizer. All other authors have declared no conflicts of interest.