Notch pathway inhibition with crenigacestat (LY3039478) in a phase I first-in-human clinical trial for patients with relapsed or refractory non-Hodgkin lymphoma and B-cell chronic lymphocytic leukemia.

ABSTRACT:

Background

Deregulated Notch signaling is implicated in non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Crenigacestat (LY3039478) prevents cleavage of Notch proteins and may benefit patients with relapsed or refractory NHL or CLL.

Objectives

This phase I clinical trial assessed the safety and efficacy of crenigacestat in patients with relapsed or refractory NHL and CLL. The main objectives were to characterize the safety profile, to confirm the recommended phase II dose of crenigacestat in patients with hematological malignancies, and to assess preliminary antitumor activity.

Design

A phase I trial enrolling patients with relapsed or refractory NHL and CLL, with Notch tumor alteration based on molecular or immunohistochemistry tumor pre-screening.

SUBMITTER: Michot JM 

PROVIDER: S-EPMC12317248 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature