Adagene Reports muzastotug Study Results, 20mg/kg Cohort Confirms ORR of 31%

Adagene (ADAG) announced results from the latest data cut from its Phase 1b/2 study of muzastotug in patients with advanced microsatellite stable colorectal cancer with no liver metastases. FDA has designated muzastotug in combination with Merck's (MRK) anti-PD-1 therapy, Keytruda, as a Fast Track product for adult patients with microsatellite stable metastatic colorectal cancer without current or active liver metastases. Previous results from a data cut on April 22, 2025 were presented at ASCO in June 2025. As of the latest data cut on January 24, a total of 67 MSS CRC patients with no liver metastases, including those with peritoneal involvement, have been treated with muzastotug at a dose of either 10 mg/kg or 20 mg/kg, in combination with pembrolizumab. The 10 mg/kg dose was administered once every three weeks or once every six weeks. The 20 mg/kg dose was administered once as a loading dose, followed by 10 mg/kg every three weeks, or 20 mg/kg every six weeks. Among 65 efficacy-evaluable patients in the dose expansion phase, those in the combined 10 mg/kg cohorts demonstrated an ORR of 13%, which was comprised of an ORR of 0% in the Q6W regimen cohort and an ORR of 17% in the Q3W cohort. The higher response rates in the Q3W cohort and robust safety, to keep patients stable without new lesions, in the Q6W cohort helped inform the decision for the dosing regimens utilized in Arm A of the ongoing randomized Phase 2 trial. The combined 20 mg/kg cohorts demonstrated a confirmed ORR of 31%, including 25% in the Q6W cohort and 36% in the 20 mg/kg loading dose cohort. The higher response rate in the 20 mg/kg cohorts helped inform the 20 mg/kg induction/maintenance dosing regimen utilized in Arm B of the ongoing randomized Phase 2 trial. Median progression-free survival was 4.8 months in the 10 mg/kg cohorts and 6.7 months in the 20 mg/kg cohorts. Notably, median PFS was 15.4 months among the 14 patients in the 20 mg/kg loading dose cohort, compared with 4.9 months among the 12 patients in the 20 mg/kg Q6W cohort, further supporting the induction/maintenance approach now being evaluated in the ongoing randomized Phase 2 study. As of the January 24 data cutoff, across 67 patients in all cohorts, there was a low 4% overall discontinuation rate, no dose limiting toxicities, and no treatment-related Grade 4 or 5 adverse events. Grade 3 TRAEs were 15% in the combined 10 mg/kg cohorts and 38% in the combined 20 mg/kg cohorts, which were generally transient and manageable. The most common treatment-related adverse events were pruritus, fatigue, hypothyroidism, and diarrhea. Regarding GI-related adverse events, the overall incidence of diarrhea, colitis and immune-mediated enterocolitis was relatively low, and such events were generally transient and manageable. The three patients with Grade 3 colitis had all recovered at the time of data cut-off. Infliximab use was low, with approximately 10% of patients requiring its use for management of GI toxicity.