In a phase 1b clinical trial, 12 women with advanced TNBC and 12 with HR-positive breast cancer were treated with entinostat (an HDAC inhibitor) + nivolumab + ipilimumab. Treatment was generally safe and well tolerated, with expected rates of AEs and no dose-limiting toxicities. In patients with TNBC, the ORR was 40% and the clinical benefit rate (CBR) was 60%, while in patients with HR-positive disease, the ORR was 25% and the CBR was 20%. PFS and OS rates were also better in patients with TNBC versus HR+ disease. Changes in myeloid cells, including evidence of increased antigen presentation, were linked to responses.
Contributed by Lauren Hitchings
ABSTRACT:We report the results of 24 women, 50% (N = 12) with hormone receptor-positive breast cancer and 50% (N = 12) with advanced triple-negative breast cancer, treated with entinostat + nivolumab + ipilimumab from the dose escalation (N = 6) and expansion cohort (N = 18) of ETCTN-9844 ( NCT02453620 ). The primary endpoint was safety. Secondary endpoints were overall response rate, clinical benefit rate, progression-free survival and change in tumor CD8:FoxP3 ratio. There were no dose-limiting toxicities. Among evaluable participants (N = 20), the overall response rate was 25% (N = 5), with 40% (N = 4) in triple-negative breast cancer and 10% (N = 1) in hormone receptor-positive breast cancer. The clinical benefit rate was 40% (N = 8), and progression-free survival at 6 months was 50%. Exploratory analyses revealed that changes in myeloid cells may contribute to responses; however, no correlation was noted between changes in CD8:FoxP3 ratio, PD-L1 status and tumor mutational burden and response. These findings support further investigation of this treatment in a phase II trial.
Author Info: (1) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. evanthia.roussostorres@med.usc.edu. Department of Medicine, Division of Medical
Author Info: (1) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. evanthia.roussostorres@med.usc.edu. Department of Medicine, Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. evanthia.roussostorres@med.usc.edu. (2) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. (3) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. (4) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. (5) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. (6) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. University of Miami Miller School of Medicine, Miami, FL, USA. (7) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. (8) University of Pittsburgh Cancer Institute and UPMC Cancer Center, Pittsburgh, PA, USA. (9) Yale Cancer Center, New Haven, CT, USA. (10) City of Hope, Duarte, CA, USA. (11) Cedars-Sinai Cancer, Los Angeles, CA, USA. (12) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. (13) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. (14) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. (15) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. (16) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. (17) Cancer Therapy Evaluation Program (CTEP), National Cancer Institute, Bethesda, MD, USA. (18) Cancer Therapy Evaluation Program (CTEP), National Cancer Institute, Bethesda, MD, USA. (19) Division of Pharmaceutics and Pharmacology, The Ohio State University, Columbus, OH, USA. (20) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. (21) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. (22) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. (23) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. (24) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. (25) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. (26) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. (27) Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA. roisin.connolly@ucc.ie. Cancer Research @UCC, College of Medicine and Health, University College Cork, Cork, Ireland. roisin.connolly@ucc.ie.
