Mersana Therapeutics (MRSN) Study Update summary

Study background and objectives

• Emi-Le (emiltatug ledadotin, XMT-1660) is a B7-H4-targeting ADC developed to address efficacy and safety limitations of current ADCs in solid tumors, especially breast cancer.

• B7-H4 is highly expressed in TNBC, endometrial, ovarian, and HR+ breast cancers, with limited expression in healthy tissue.

• Emi-Le received FDA Fast Track designation for advanced/metastatic TNBC and HER2-low/negative breast cancer post-topo-1 ADC.

• The Phase 1 trial uses a Bayesian Optimal Interval design to establish safety, tolerability, and preliminary efficacy, with dose escalation and backfill cohorts across multiple tumor types.

• B7-H4 expression is assessed retrospectively using tumor proportion scores (TPS) to inform biomarker strategy and optimize expansion cohorts.

Patient demographics and trial design

• 130 patients dosed as of December 13, 2024, with the majority having breast cancer and prior exposure to topo-1 ADCs.

• Median age was 55, with a median of 4.5 prior lines of therapy; 60% had received prior topo-1 ADCs.

• Dose escalation and backfill cohorts investigated a broad range of doses and schedules, with expansion at 67.4 mg/m² Q4W in TNBC post-topo-1 ADC.

• B7-H4 high expression (TPS ≥70) was present in 43.7%–45% of patients with known status.

• Additional cohorts included HR+ breast, endometrial, ovarian, and adenoid cystic carcinoma.

Safety and tolerability findings

• No grade 4 or 5 treatment-related adverse events (TRAEs) were reported among 130 patients.

• Most common TRAEs were transient AST increases, low-grade nausea, fatigue, and reversible proteinuria.

• Grade 3 TRAEs occurred in 30% of patients; 4.6% experienced treatment-related serious adverse events.

• Dose-limiting toxicities included transient grade 3 AST elevations, reversible grade 3 proteinuria, and grade 3 pyrexia.

• Proteinuria was generally asymptomatic and reversible, with mitigation strategies including ACE inhibitors, ARBs, SGLT2s, and dose reduction instead of delay.