Syndax to Begin Phase 1b Trial of Revumenib for Relapsed/Refractory Metastatic MSS CRC

Syndax Pharmaceuticals, a clinical-stage biopharmaceutical firm based in Waltham, Massachusetts, has announced the progression of its Phase 1/2 trial for revumenib, a selective oral menin inhibitor, into the Phase 1b stage. This advancement follows the recommendation of the Independent Data Monitoring Committee (IDMC) after a favorable safety review of the initial Phase 1a trial data. The study focuses on the use of revumenib as a monotherapy in patients with relapsed or refractory (R/R) metastatic microsatellite stable (MSS) colorectal cancer (CRC).

Dr. Neil Gallagher, Syndax's President and Head of Research and Development, expressed optimism over the initial results from Phase 1a. The trial revealed a promising safety profile and early efficacy signals, including a 33% stable disease rate at 16 weeks, which is encouraging compared to the current standard treatments. These findings support moving forward to the Phase 1b portion of the trial, as the company prepares for potential launches of revumenib and another drug, axatilimab, later this year. Gallagher emphasized the ongoing commitment to understanding revumenib’s role in treating R/R metastatic MSS CRC.

The Phase 1/2 trial (NCT05731947) aims to evaluate the safety, tolerability, and anti-tumor activity of revumenib in patients with relapsed or refractory metastatic MSS CRC. During the Phase 1a stage, 19 patients participated, each having undergone a median of four previous treatments. These patients were divided into three dose cohorts: 163 mg, 226 mg, and 276 mg, administered three times a day (TID). Revumenib demonstrated a well-tolerated safety profile with no Grade 3 or higher treatment-related adverse events (TRAEs). The most common TRAEs included decreased appetite, dysgeusia, nausea, and fatigue.

Efficacy results from Phase 1a showed that revumenib could potentially curb disease progression in R/R patients with metastatic MSS CRC. At dose levels believed to achieve full target saturation (226 mg and 276 mg TID), 44% of patients achieved stable disease at 8 weeks, and 33% maintained stable disease at 16 weeks. Notably, one patient continued on the study for 32 weeks due to prolonged stable disease. Consequently, the 276 mg TID dosage was chosen for the Phase 1b trial.

Metastatic MSS CRC is the second leading cause of cancer deaths in the United States, with more than 55,000 cases annually in the R/R setting. The activation of the Wnt/β-catenin signaling pathway is critical in the development and growth of most CRC tumors. The menin-MLL1 protein complex regulates β-catenin activity, and blocking this complex with menin inhibitors like revumenib has shown potential in preclinical models for halting tumor growth.

Revumenib, developed by Syndax Pharmaceuticals, is a potent, selective inhibitor targeting the menin-KMT2A interaction, intended for treating various acute leukemias, including KMT2A-rearranged (KMT2Ar) and mutant nucleophosmin (mNPM1) leukemias. The drug has received multiple designations from the FDA and European Commission, including Orphan Drug Designation and Breakthrough Therapy Designation, reflecting its potential significance in treating these conditions. The pivotal AUGMENT-101 trial has shown positive results, with data from ongoing studies expected to further elucidate its efficacy.

Syndax continues to develop its pipeline of cancer therapies, with revumenib and axatilimab being key highlights. As the company advances its clinical trials, it remains focused on potential market launches and further exploration of its innovative treatments.