Abstract PD1-6: Inhibition of PD-L1 by MPDL3280A leads to clinical activity in patients with metastatic triple-negative breast cancer

Abstract

Abstract Background: Metastatic triple-negative breast cancer (TNBC) is associated with a poor prognosis and has no targeted therapy options. Programmed death-ligand 1 (PD-L1) expression is more prevalent in TNBC than in other breast cancer subtypes. PD-L1 may protect cancer cells from immune-mediated destruction by binding to its receptors PD-1 and B7.1. MPDL3280A, a human anti-PD-L1 monoclonal antibody with an engineered Fc-domain designed for optimized efficacy and safety, blocks PD-L1 activity and restores tumor-specific T-cell immunity. Methods: This multicenter Phase I study selectively enrolled a cohort of patients with PD-L1-positive metastatic TNBC. PD-L1 positivity was centrally evaluated based on the PD-L1 immunohistochemistry (IHC) status of tumor-infiltrating immune cells (ICs). Eligible patients received MPDL3280A 15 or 20 mg/kg IV every 3 weeks for up to 1 year. The objective response rate (ORR) was assessed by RECIST v1.1. MPDL3280A immune correlates were evaluated for tumor and circulating biomarkers. The clinical data cutoff was January 1, 2014. Results: Twelve patients were treated with MPDL3280A and evaluable for safety. Patients had ECOG PS 0-1 (33% ECOG PS 1), and the median age was 55 years (range, 29-72 years). All 4 patients (33%) with visceral metastases had liver metastases, and 1 patient (8%) had bone metastases. 92% of patients received ≥ 2 prior therapies. Prior chemotherapies included anthracycline (92%), taxane (75%) and platinum (42%). Grade 3-4 treatment-related adverse events (AEs) occurred in 8% of patients (1 event of Grade 3 adrenal insufficiency). One patient had an immune-related AE (Grade 2 pyrexia). No treatment-related deaths were observed. Nine patients were dosed by November 16, 2013 and evaluable for efficacy. The ORR was 33%, including 1 CR and 2 PRs. Responders included patients with visceral metastases at baseline. At the time of the clinical data cut-off, all responses occurred within 6 weeks of the first dosing of MPDL3280A, and all of the responses were ongoing. The median duration of response had not been reached. One patient achieved stable disease as best response. Two additional patients had tumor shrinkage (-43% and -44% change in target lesions, respectively) but were not counted as RECIST responders due to the appearance of new lesions, which is likely attributable to pseudoprogression. Preliminary pharmacodynamic biomarkers related to MPDL3280A activity, including circulating plasma markers and tumor immunomonitoring with CD8 IHC, will be presented along with updated clinical data. Conclusions: MPDL3280A treatment was well tolerated and was associated with objective clinical activity in patients with pretreated metastatic TNBC. Further evaluation of the safety and clinical activity of MPDL3280A in both PD-L1-positive and PD-L1-negative metastatic TNBC is ongoing. Clinical trial information: NCT01375842. Citation Format: Leisha A Emens, Fadi S Braiteh, Philippe Cassier, Jean-Pierre DeLord, Joseph Paul Eder, Xiaodong Shen, Yuanyuan Xiao, Yan Wang, Priti S Hegde, Daniel S Chen, Ian Krop. Inhibition of PD-L1 by MPDL3280A leads to clinical activity in patients with metastatic triple-negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr PD1-6.