Syndax Pharmaceuticals announced that it has advanced into the Phase 1b portion of its Phase 1/2 proof-of-concept trial of revumenib, the Company's highly selective, oral menin inhibitor, as a monotherapy in patients with relapsed or refractory (R/R) metastatic microsatellite stable (MSS) colorectal cancer (CRC). The Company's decision was supported by the trial's Independent Data Monitoring Committee (IDMC) following its recent pre-planned review of initial data from the Phase 1a portion of the trial. The Phase 1/2 trial (NCT05731947) is designed to assess the safety, tolerability, and anti-tumor activity of revumenib in patients with relapsed or refractory metastatic MSS CRC.

The Phase 1a dose escalation portion of the trial enrolled a total of 19 patients who had a median of four prior therapies across three dose cohorts, including 163 mg, 226 mg, and 276 mg three times a day (TID).  Revumenib was well-tolerated at all dose levels tested and the safety profile was consistent with the Company's previously reported data. No Grade 3 or greater treatment-related adverse events (TRAEs) were observed and the most common TRAEs were decreased appetite, dysgeusia, nausea, and fatigue.  In addition, the initial efficacy results provide early clinical support that revumenib may be able to impact disease progression in R/R patients with metastatic MSS CRC.

At doses believed to achieve full target saturation, dose levels 2 and 3, 44% (4/9) of patients had stable disease at 8 weeks, and 33% (3/9) of patients had stable disease at 16 weeks.  One patient with prolonged stable disease remained on study for 32 weeks. Based on the initial data, 276 mg TID was selected as the go-forward dose in the Phase 1b portion.