Immunome (IMNM) Study Result summary

Study design and objectives

• RINGSIDE was a global, randomized, double-blind, placebo-controlled Phase 3 trial enrolling 156 patients with progressing desmoid tumors, randomized 1:1 to varegacestat or placebo, with crossover allowed upon progression.

• The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR), tumor volume reduction, pain intensity, duration of response, and safety.

• Patients received varegacestat 1.2 mg daily or placebo until disease progression or death, with an ongoing open-label extension phase.

Key efficacy results

• Varegacestat achieved an 84% reduction in risk of disease progression versus placebo (hazard ratio 0.16, p<0.0001).

• Confirmed ORR was 56% for varegacestat compared to 9% for placebo, a statistically significant difference (p<0.0001).

• Median best percentage reduction in tumor volume was 83% for varegacestat versus an 11% increase with placebo.

• All key secondary endpoints were met, including significant improvements in tumor volume reduction and pain intensity.

• No patients on varegacestat had progressive disease as their best response.

Safety and tolerability

• Varegacestat was generally well tolerated, with most adverse events being grade 1 or 2; no deaths occurred.

• Most common adverse events were diarrhea (82%), fatigue (44%), rash (43%), nausea (35%), and cough (34%).

• Ovarian toxicity occurred in 55.6% of women of childbearing potential, with most recovering function by data cutoff.

• The safety profile was consistent with the GSI class, but ovarian toxicity rates were lower than with nirogacestat.