Safety and efficacy of pembrolizumab (pembro) plus capecitabine (cape) in metastatic triple negative breast cancer (mTNBC).

1033 Background: In mTNBC, anti-PD-1/L1 monotherapy was associated with objective response rates (ORR) of 23-26% in the first-line setting, but ORR of 5-6% in later lines. We hypothesize that concurrent pembro plus standard-of-care chemotherapy is safe, and may increase clinical benefit by allowing for earlier treatment with anti-PD-1, when tumor burden and iatrogenic immunosuppression are minimized. This is the first study to explore the combination cape with PD-1/L1 blockade in breast cancer. Methods: In a pilot/phase II study, we evaluate the tolerability and preliminary efficacy of concurrent pembro (200mg IV q21 day) plus investigator-selected 1st/2nd line paclitaxel (80mg/m2 IV weekly) or oral cape (2,000mg BID, weekly 1 on/1 off). The primary endpoint of the pilot phase is tolerability, defined as the proportion of subjects receiving > 6 weeks concurrent therapy without dose discontinuation. Toxicities are reported per CTCAE v4.0. The secondary endpoint is 12-week ORR by RECIST1.1, with potential phase II expansion according to a Simon 2-stage design (if ≥4/14 ORR). Exploratory objectives include intratumoral/peripheral immunologic assessments by T-cell receptor sequencing, multispectral immunofluorescence, and real-time multi-parametric flow cytometry. Here, we report the results of the pilot phase of the cape cohort (NCT02734290). Results: As of 1/1/2018, 100% (9/9) of safety-evaluable subjects tolerated concurrent cape+pembro for at least 6 weeks. Toxicities were generally consistent with monotherapy experience (diarrhea: grade I-II 56%; hand-foot: grade I-II 67%), and improved with dose-reduction. Partial responses have been observed in three subjects, two having metaplastic pathology. A fourth subject experienced durable stable disease, with ongoing response at 48 weeks. Conclusions: This study met the primary endpoint of safety for cape plus pembro in mTNBC and the combination will be explored for efficacy in the next stage of this study. These data may also inform the evaluation of concurrent anti-PD-1/L1 plus cape in the adjuvant setting. Clinical trial information: NCT02734290.