KEY TAKEAWAYS
- The phase I/II trial aimed to evaluate the efficacy and safety of BMS-986158, a BET inhibitor, in combination with RUX or FED in intermediate-risk or high-risk MF patients.
- The primary objectives were safety, tolerability, and MTD.
- The study showed manageable safety profiles with robust SPR in intermediate-risk or high-risk MF patients, and the trial is ongoing.
Bromodomain and extraterminal domain inhibitors (BETi), such as BMS-986158, have shown promise in combination with JAK inhibitors for treating myelofibrosis(MF).
Researchers aimed to evaluate the efficacy and safety of BMS-986158, a BET inhibitor, in combination with ruxolitinib(RUX) or fedratinib (FED) in intermediate-risk or high-risk MF patients.
The study involved administering BMS-986158 with RUX in RUXnaïve patients (Part 1A; first-line [1L] MF) or with FED in RUX-exposed patients(Part 1B; second-line MF).
The primary objectives were to assess safety tolerability and determine the maximum tolerated dose(MTD) and/or recommended Phase II dose. Secondary objectives include evaluating spleen volume reduction (SVR) and an exploratory assessment of JAK2 variant allele frequency.
In Part 1A, 11 patients (median age 67 [range, 36–81]) were treated, while Part 1B included 12 patients (median age 69 [range, 37–77]). Any-grade treatment-related adverse events (TRAEs) were observed in 82% of Part 1A patients and 75% of Part 1B patients.
Grade 3/4 TRAEs in Part 1A included thrombocytopenia (n=5, 45%), neutropenia, hypertension, and anemia (n=1 each, 9%). In Part 1B, Grade 3/4 TRAEs included thrombocytopenia and anemia ((n=5 each, 42%), diarrhea, and blood bilirubin increase (8% each).
Dose-limiting toxicities(DLTs) occurred in 2 patients in Part 1A (2.0 and 3.75 mg BMS-986158, both thrombocytopenia) and 3 in Part 1B (1.25 mg BMS-986158; diarrhea, thrombocytopenia, elevated bilirubin).
No discontinuations due to TRAEs were reported in Part 1A.SVR was observed at Week 12 in all evaluable patients in Part 1A, deepening further at Week 24.
In Part 1A, 5 /6 and 6/6 patients receiving BMS-986158 (2.0 or 3.0 mg) with RUX achieved SVR35 at Weeks 12 and 24, respectively. In Part 1B, none of the patients at Week 12 and 1 out of 3 at Week 24 receiving BMS-986158 (0.5 or 0.75 mg) with FED achieved SVR35.
Reductions in JAK2V617F frequency were observed in Part 1A (35% maximum reduction by Cycle 10, n=4) and Part 1B (22% maximum reduction by Cycle 7, n=2).
The study showed manageable safety profiles with robust spleen volume reduction in intermediate-risk or high-risk MF patients, and the trial is ongoing.
Source: https://clml-soho2023.elsevierdigitaledition.com/392/index.html
Clinical Trial: https://www.clinicaltrials.gov/study/NCT04817007
Ayala R, Lopez N, Shacham Abulafia A, Alwan M, Yannakou CK, Raman I, Ribrag V, Fong CY, Volchek Y, Bonifacio M, Tucci A, Kiladjian JJ, Hernandez Rivas JM, Xicoy B, Al-Ali H, Ianotto JC, Lee-Hoeflich ST, Das S, Wu B, Ravindran P, Zhao Q, Wang G, Esposito O, Liu Y, Nikolova Z, Tehlirian C, Coker S, Lavie D. BMS‑986158, a Potent Bromodomain and Extraterminal Domain Inhibitor (BETi), as Monotherapy and in Combination With Ruxolitinib (RUX) or Fedratinib (FED) in Intermediate‑Risk or High‑Risk Myelofibrosis (MF): Results From a Phase I/II Study.
