KEY TAKEAWAYS
- The phase 1 trial aimed to tailor the optimal doses of BMF-219 and explore early activity across diverse blood cancers.
- The primary objective was the safety of DLTs and AEs. The Secondary objectives were ORR, DOR, PFS, and TTP across varied blood cancers.
- The ongoing trial awaits the final result to establish safe BMF-219 dosing in r/r cancers.
For this phase 1 trial, researchers aimed to find the best dose of BMF-219 (oral, taken alone) for different types of cancer and groups of patients (pts). They independently establish the optimal biological dose (OBD) and recommended phase II dose (RP2D) for BMF-219 oral monotherapy in each cohort/indication, with key secondary objectives including safety and tolerability assessment, pharmacokinetics/pharmacodynamics characterization, and antitumor activity evaluation.
The study will use an accelerated titration method, and the dose will escalate in single-subject cohorts for each indication until 1 patient experiences grade ≥2 adverse events(AEs) or dose-limiting toxicity (DLT). At that point, the cohort will switch to a classical “3 + 3” design. Treatment continues in 28-day cycles until progression or intolerability, with expansion cohorts at the OBD/RP2D enrolling pts for additional safety and efficacy data.
The trial will be conducted on R/R AL patients who were facing standard-therapy failure or ineligibility, DLBCL individuals with a history of at least 2 prior therapies, MM patients having received at least 3 prior therapies, and CLL/SLL individuals with a minimum of 2 prior therapies.
In the escalation phase, patients will undergo escalating oral doses of BMF-219 once daily in continuous 28-day cycles, aiming to determine the OBD/RP2D for each cohort/indication.
Alternatively, a twice-daily dosing regimen may be employed. During the expansion phase, BMF-219 will be orally administered at the determined OBD/RP2D.
Source: https://clml-soho2023.elsevierdigitaledition.com/310/index.html
Clinical Trial: https://clinicaltrials.gov/study/NCT05153330
Ravandi F, Lancet J, Alegre Amor A, Badar T, Barrientos J, Bashey A, Bergua Burgues JM, Curran E, Janssen J, Jeyakumar D, Kishtagari A, Montesinos P, Morillo D, Rosenberg A, Schiller G, Ahmed U, Cacovean A, Morris S, Follit C, Mandap C, Butler T, Carraway H. COVALENT‑101: Phase I Study of BMF‑219, a Covalent Menin Inhibitor, in Adult Patients With AML, ALL (With KMT2A/MLL1 Rearrangements, NPM1 Mutation), DLBCL, MM, and CLL/SLL (NCT05153330). Scopus SOHO 2323 AML-522.
