Cogent Biosciences (COGT) Study Result summary

Study background and design

• SUMMIT was a double-blind, placebo-controlled trial evaluating bezuclastinib versus placebo in 179 patients with moderate-to-severe non-advanced systemic mastocytosis (SM), randomized 2:1 for 24 weeks, followed by open-label extension.

• Inclusion criteria included age ≥18, confirmed non-advanced SM, moderate-to-severe symptoms, and prior KIT inhibitor therapy allowed.

• The patient population included indolent SM, smoldering SM, and bone marrow mastocytosis, with a median age of 51 and 66% female.

• Baseline measures showed high symptom scores and mast cell burden, representative of the target group.

• Prior use of KIT inhibitors was reported in 12% of patients.

Efficacy results

• Bezuclastinib met all primary and key secondary endpoints, achieving statistically significant and clinically meaningful reductions in total symptom score at week 24 (mean change 24.32 vs. 15.41 for placebo, p=0.0002; placebo-adjusted effect size 8.91).

• 87.4% of bezuclastinib patients achieved at least a 50% reduction in serum tryptase versus 0% for placebo (p<0.0001).

• Significant reductions were observed in KIT D816V variant allele frequency and bone marrow mast cell burden.

• Consistent improvements were seen using both MS2D2 and ISM-SAF composite symptom scores.

• Case studies highlighted dramatic and sustained symptom and biomarker improvements, with some patients discontinuing supportive medications.

Safety and tolerability

• Bezuclastinib demonstrated a favorable and manageable safety profile; most adverse events (AEs) were low grade and reversible, with 98.3% of TEAEs in the bezuclastinib arm.

• Common AEs included hair color changes (69–69.5%), altered taste (23.7%), nausea (22%), and mild liver enzyme elevations (ALT/AST 22%).

• Serious AEs were rare and similar or lower in bezuclastinib versus placebo; discontinuations due to ALT/AST elevations were 5.9%, all resolved after discontinuation.

• No hepatic AEs required hospitalization or intervention; routine lab monitoring is expected and not a barrier to prescribing.

• Some AEs, such as dizziness and fatigue, occurred more frequently in the placebo group.