Entinostat, nivolumab and ipilimumab for women with advanced HER2-negative breast cancer: a phase Ib trial.
Evanthia T Roussos TorresWon Jin HoLudmila DanilovaJoseph A TandurellaJames LeathermanChristine RafieChenguang WangAdam M BrufskyPatricia M LoRussoVincent ChungYuan YuanMelinda DownsAshley O'ConnorSarah M ShinAlexei HernandezElizabeth L EngleRichard PiekarzHoward StreicherZahra TalebiMichelle A RudekQingfeng ZhuRobert A AndersAshley Cimino-MathewsElana J FertigElizabeth D ThompsonVered StearnsCaitriona CahirPublished in: Nature cancer (2024)
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.
Keyphrases
- free survival
- positive breast cancer
- regulatory t cells
- induced apoptosis
- open label
- bone marrow
- clinical trial
- type diabetes
- polycystic ovary syndrome
- randomized controlled trial
- single cell
- adipose tissue
- acute myeloid leukemia
- pregnant women
- oxidative stress
- skeletal muscle
- nk cells
- newly diagnosed
- combination therapy
- cervical cancer screening