Safety of MEDI4736 (anti-PD-L1 antibody) administered concomitant with weekly nab-paclitaxel and dose dense doxorubicin/cyclophosphamide (ddAC) as neoadjuvant chemotherapy for stage I-III triple negative breast cancer (TNBC): A Phase I/II trial.

Abstract

572 Background: Pathologic complete response (pCR) rates to neoadjuvant chemotherapy in TNBC plateaued at 40% with existing regimens, the co-administration of an immune checkpoint inhibitor might increase pCR rate. The objective of the Phase I portion of this trial was to assess the safety of administering MEDI4736 concomitant with sequential taxane and anthracycline chemotherapy. Methods: The Phase I part followed the 3+3 design exploring two dose levels of MEDI4736 (3 and 10 mg/kg iv q2wk) in combination with weekly nab-paclitaxel (100 mg/m2) x 12 followed by ddAC x 4. Dose limiting toxicities (DLT) were evaluated during the entire 20 weeks of therapy and were defined as (1) gr 4 immune related adverse event (irAE), (2) gr 3 irAE that did not resolve to gr 2 within 3 days or to ≤ gr 1 within 14 days, (3) > gr 3 colitis or pneumonitis, (4) ≥ gr 3 non-irAE causally related to MEDI4736. Results: 3 patients completed therapy at the 3 mg/kg dose without any DLT, 1 additional patient refused further study medication because of recurrent gr 2 fatigue after 7 weeks of therapy. At the 10 mg/kg dose level, all 3 patients completed the nab-paclitaxel+MEDI4736 treatment without any DLT and 2 patients also completed 3 of the 4 planned treatments with ddAC without DLT. Among all 7 patients who started therapy, 1 at the 3 mg/kg group experienced gr 3 dehydration and dyspnea without chest X ray abnormalities which resolved within 48 hours with hydration. There were no other gr 3 AEs. Among the 3 patients who have completed therapy as per protocol (not including the patient who withdraw consent), 1 achieved pCR, 1 had minimal, and 1 had extensive residual cancer. No surgical AE were seen. All patients at the 10 mg/kg dose level will complete surgery by March 2017 and final Phase I toxicity and efficacy results will be presented. Conclusions: Concomitant administration of MEDI4736 10 mg/kg with weekly nab-paclitaxel and subsequently with ddAC neoadjuvant chemotherapy appears safe. The Phase II portion of the trial is open and will accrue a maximum of 50 patients to assess the efficacy of the combination. Clinical trial information: NCT02489448.