Results from a First-in-Human Phase I Study of Siremadlin (HDM201) in Patients with Advanced Wild-Type TP53 Solid Tumors and Acute Leukemia.

ABSTRACT:

Purpose

This phase I, dose-escalation study investigated the recommended dose for expansion (RDE) of siremadlin, a p53-MDM2 inhibitor, in patients with wild-type TP53 advanced solid or hematologic cancers.

Patients and methods

Initial dosing regimens were: 1A (day 1; 21-day cycle; dose 12.5-350 mg) and 2A (days 1-14; 28-day cycle; dose 1-20 mg). Alternative regimens included 1B (days 1 and 8; 28-day cycle) and 2C (days 1-7; 28-day cycle). The primary endpoint was incidence of dose-limiting toxicities (DLT) during cycle 1.

Results

Overall, 115 patients with solid tumors and 93 with hematologic malignancies received treatment. DLTs occurred in 8/92 patients with solid tumors and 10/53 patients with hematologic malignancies. In solid tumors, an RDE of 120 mg was defined

SUBMITTER: Stein EM 

PROVIDER: S-EPMC9377734 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature