TY - JOUR
T1 - Entinostat, nivolumab and ipilimumab for women with advanced HER2-negative breast cancer
T2 - a phase Ib trial
AU - Roussos Torres, Evanthia T.
AU - Ho, Won J.
AU - Danilova, Ludmila
AU - Tandurella, Joseph A.
AU - Leatherman, James
AU - Rafie, Christine
AU - Wang, Chenguang
AU - Brufsky, Adam
AU - LoRusso, Patricia
AU - Chung, Vincent
AU - Yuan, Yuan
AU - Downs, Melinda
AU - O’Connor, Ashley
AU - Shin, Sarah M.
AU - Hernandez, Alexei
AU - Engle, Elizabeth L.
AU - Piekarz, Richard
AU - Streicher, Howard
AU - Talebi, Zahra
AU - Rudek, Michelle A.
AU - Zhu, Qingfeng
AU - Anders, Robert A.
AU - Cimino-Mathews, Ashley
AU - Fertig, Elana J.
AU - Jaffee, Elizabeth M.
AU - Stearns, Vered
AU - Connolly, Roisin M.
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.
PY - 2024/6
Y1 - 2024/6
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85185112148
U2 - 10.1038/s43018-024-00729-w
DO - 10.1038/s43018-024-00729-w
M3 - Article
C2 - 38355777
AN - SCOPUS:85185112148
SN - 2662-1347
VL - 5
SP - 866
EP - 879
JO - Nature Cancer
JF - Nature Cancer
IS - 6
ER -
