Bosmolisib (BR101801), a novel PI3K-δ/γ and DNA-PK inhibitor for relapsed/refractory patients with peripheral T-cell lymphoma: a phase I study

作者：Tae Min Kim, Seok Jin Kim, Jin Seok Kim, Deok‐Hwan Yang, Dok Hyun Yoon, Won Sik Lee, Eunyoung Lee, Jeong-Ok Lee, Ahmad Mattour, Jorge Chaves, Bong-Seog Kim · 发表于：Blood Cancer Journal · 年份：2026 · DOI：10.1038/s41408-026-01600-0 · 研究领域：Lymphoma Diagnosis and Treatment、Chronic Lymphocytic Leukemia Research、PI3K/AKT/mTOR signaling in cancer

Bosmolisib is a novel triple inhibitor of PI3K-δ/γ and DNA-PK for malignancy treatment. This was a first-in-human, phase 1, open-label, dose-escalation, and dose-expansion trial with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL). Patients received bosmolisib orally once daily in 28-day cycles across four dose levels (50–325 mg) until disease progression or unacceptable toxicity. The study utilized a 3 + 3 dose-escalation design to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D), followed by expansion at RP2D. Primary endpoints were safety and MTD/RP2D determination; secondary endpoints included efficacy, pharmacokinetics, and pharmacodynamics. A total of 26 patients were enrolled in dose-escalation ( N = 12) and dose-expansion ( N = 14). Median age was 65 years with a median of 3 prior therapies. Bosmolisib demonstrated acceptable tolerability; dose-limiting toxicities were observed at 325 mg (alanine transaminase [ALT] increased and erythema multiforme), establishing MTD/RP2D at 200 mg. Most adverse events (AEs) were Grade 1–2, with the most common Grade ≥3 AEs (ALT 23.1%, aspartate transaminase 15.4%). Of 23 evaluable patients, the overall response rate (ORR) was 26.1%, and in PTCL patients, ORR was 31.6% with one patient achieving a durable complete response. Pharmacodynamics profiling showed statistically significant decrease in regulatory T-cells. These findings support evaluation of bosmolisib in a phase 2 trial (ClinicalTrials.gov ...