Safety and efficacy of a small-molecule c-Myc degrader WBC100 in solid tumors: A first-in-human, phase I trial.

Abstract

3120 Background: c-Myc amplification or overexpression is involved in the development and progression of many human cancers, and is often associated with poor outcomes. It is an extraordinarily desirable target, but is also considered undruggable. WBC100 is an oral active molecule glue that selectively degrades c-Myc protein. Methods: This is a first-in-human, dose-escalation study conducted in China. Patients with solid tumors that have progressed or relapsed after standard systemic therapy were enrolled. WBC100 was orally administered every other day (QOD) according to 3+3 design. The primary endpoints were safety, dose-limiting toxicity (DLT) and maximal tolerated dose (MTD). Results: As of Dec 9, 2024, 28 patients were enrolled in seven dose levels (DLs) from 0.5 to 3.5 mg. The median age was 59 (range, 45-71) years, comprising 15 males and 13 females. Three (11%) patients had an ECOG PS score of 0, while the remaining 25 (89%) had a score of 1. The median number of prior systemic therapy lines was 3 (range, 1 to 6). One DLT of prolonged QT interval was observed in DL7, and MTD has not been reached. Six patients (21%) experienced grade 3 or higher treatment-related adverse events, including five (17.9%) neutropenia and two (7.1%) leukopenia and one (3.6%) prolonged QT interval. Increased aspartate aminotransferase, thrombocytopenia, proteinuria, increased alanine aminotransferase, fatigue, nausea, anemia, and hypoalbuminemia were the most commonly reported grade 1 or 2 adverse events. Nineteen patients were evaluable for efficacy, one (5.3%) showed partial regression (PR), and six (31.6%) showed stable disease (SD), including two patients with hepatocellular carcinoma, one with duodenal adenocarcinoma, and three with pancreatic cancer. Notably, we enrolled eight patients with pancreatic cancer at DL6 and DL7, and six of them were evaluable for efficacy, with one (16.7%) PR and two (33.3%) SD. Conclusions: WBC100 showed a tolerable safety profile and preliminary anti-tumor activity in advanced solid tumors especially in PDAC. Dose escalation is ongoing and expected to proceed to dose expansion soon. To our knowledge, this is the first study of a small-molecule c-Myc degrader for further clinical development in cancer. Clinical trial information: NCT05100251 .