Anti-PD-L1 Antibody Demonstrates Antitumor Activity in Triple-Negative Breast Cancer
Report from a phase 1 trial presented at the 2015 AACR annual meeting.
The anti-PD-L1 monoclonal antibody MPDL3280A demonstrated antitumor activity in heavily pretreated patients with metastatic triple-negative breast cancer (TNBC), according to results from a phase 1 trial reported at the 2015 American Association for Cancer Research (AACR) Annual Meeting.
“TNBC is a good target for cancer immunotherapy—in particular those that target PD-L1—for several reasons,” stated Leisha A. Emens, MD, PhD, of Johns Hopkins University School of Medicine in Baltimore, MD, which include its high mutation rate, the higher number of tumor-infiltrating lymphocytes, and greater level of PD-L1 expression compared with other breast cancer subtypes. MPDL3280A binds to the PD-L1 present on tumor cells, preventing the interaction of PD-L1 with PD-1 and B7.1, which are located on T cells.
This multicenter, phase 1a expansion trial evaluated safety, efficacy, and potential biomarkers related to response of MPDL3280 A in TNBC, as well as melanoma, non-small cell lung cancer, renal cell carcinoma, UBC, and other solid cancers.
This analysis is of the patients with metastatic TNBC, who received either intravenous 15 mg/kg, 20 mg/kg or a 1,200 mg flat dose administered every 3 weeks.
Patients were evaluated according to the RECIST v1.1 criteria for disease response, and PD-L1 levels in archival or fresh biopsies were analyzed by immunohistochemistry.
Multiplex immunoassay and FACS were used to assess other peripheral biomarkers. Initially, patients were selectively enrolled in the study based on PD-L1 expression levels greater than 5%; however, the trial has since enrolled patients with TNBC regardless of PD-L1 expression.
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The median age of the 54 safety-evaluable patients was 48, and the ECOG performance status was 0 (52%) or 1 (44%). At baseline, visceral metastasis was present in 70% of patients and bone metastases in 24% of patients.
In addition, most patients had received a minimum of 4 previous therapies including anthracyclines (85%), taxanes (74%), and platinum agents (57%).