14P - KEYNOTE-012: A phase Ib study of pembrolizumab (MK-3475) in patients (pts) with metastatic triple-negative breast cancer (mTNBC)

Date 07 May 2015
Event IMPAKT 2015
Session Welcome reception and Poster Walk
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Metastatic
Cancer Immunology and Immunotherapy
Presenter Laurence Buisseret
Citation Annals of Oncology (2015) 26 (suppl_3): 6-9. 10.1093/annonc/mdv115
Authors L. Buisseret1, J. Specht2, E..C. Dees3, R. Berger4, S. Gupta5, R. Geva6, L. Pusztai7, C.K. Gause8, V. Karantza9, R. Nanda10
  • 1Medical Oncology Clinic, Institute Jules Bordet, 10000 - Brussels/BE
  • 2Medical Oncology, University of Washington Seattle Cancer Care Alliance, 98019 - Seattle/US
  • 3Clinical Research - Breast Cancer, Lineberger Comprehensive Cancer Center University of North Carolina, Chapel Hill/US
  • 4Medical Oncology, Sheba Medical Center, Tel Hashomer/IL
  • 5Genitourinary Oncology, H. Lee Moffitt Cancer Center University of South Florida, 33612 - Tampa/US
  • 6Dept. Of Oncology, Tel Aviv Sourasky Medical Center-(Ichilov), 64239 - Tel Aviv/IL
  • 7Yale Cancer Center, Yale University, New Haven/US
  • 8Bards, Merck & Co., Inc., Kenilworth/US
  • 9Clinical Research Oncology, Merck & Co., Inc., Kenilworth/US
  • 10Breast Medical Oncology, University of Chicago, Chicago/US



Objective: To determine efficacy and safety of pembrolizumab, a humanized IgG4 monoclonal antibody against programmed death receptor 1 (PD-1), in pts with mTNBC.

Methods: In the phase 1b KEYNOTE-012 study, women with metastatic ER/PR/HER2 breast cancer expressing programmed death receptor ligand 1 (PD-L1) received pembrolizumab 10 mg/kg every 2 weeks until disease progression or intolerable toxicity. An ECOG PS of 0 or 1, no systemic steroid therapy, and no active brain metastases were required for enrollment. PD-L1 positivity was defined as staining in the stroma or in ≥1% of tumor cells as assessed by a prototype immunohistochemistry assay using the 22C3 antibody. Adverse events (AEs) were monitored and graded per CTCAE v4.0. Response was assessed every 8 weeks per RECIST v1.1 by central review. Primary end point was the overall response rate (ORR).

Results: Of the 111 pts with evaluable mTNBC samples screened for PD-L1 expression, 65 (59%) had PD-L1–positive tumors. Of the 32 pts enrolled, mean age was 52 years, and 46.9% of pts had received ≥3 prior lines of therapy for metastatic disease. The confirmed ORR was 18.5% in the 27 pts evaluable for response per RECIST v1.1 by central review (Table). As of November 10, 2014, median follow-up duration was 9.9 months. Median time to response was 18 weeks (range, 7-32). Median duration of response was not reached (range, 15-40+ weeks), with 3 of 5 responders on treatment for ≥11 months. The 6-month progression-free survival rate was 23.3%. Treatment-related AEs occurred in 56.3% of pts and were of grade 3-5 severity in 15.6%. One case of treatment-related disseminated intravascular coagulation led to death.

Conclusions: Pembrolizumab demonstrated an acceptable safety profile and promising antitumor activity, including durable responses, in women with heavily pretreated, PD-L1–positive, mTNBC. These results support the continued development of pembrolizumab in this population.

Pts Evaluable for Response N = 27
ORR 5 (18.5%)
Best overall response
Complete response 1 (3.7%)
Partial response 4 (14.8%)
Stable disease 7 (25.9%)
Progressive disease 12 (44.4%)
No assessment 3 (11.1%)

Clinical trial identification: EudraCT number 2012-005771-14, released April 7, 2014

Disclosure: L. Pusztai: Research funding from Merck Sharp & Dohme.

C.K. Gause and V. Karantza: Employee of Merck & Co., Inc.

All other authors have declared no conflicts of interest.