Mersana Therapeutics, Inc. announced positive initial clinical data from the Phase 1 dose escalation and backfill cohorts for emiltatug ledadotin (Emi-Le; XMT-1660), Mersana?s lead Dolasynthen ADC candidate targeting B7-H4. As of a December 13, 2024 data cutoff, the dose escalation portion of the Emi-Le Phase 1 clinical trial enrolled a total of 130 patients with advanced/metastatic TNBC; hormone-receptor-positive, human epidermal growth factor receptor 2 negative breast cancer; ovarian cancer; endometrial cancer and adenoid cystic carcinoma type 1. The enrolled patient population was heavily pretreated, with patients receiving up to 15 and a median of 4.5 prior lines of therapy, and approximately 92% of enrolled patients with TNBC had been previously treated with at least one topo-1 ADC. Among the 103 patients with known B7-H4 tumor expression, approximately 44% had a tumor proportion score of 70% or higher, which Mersana has preliminarily characterized as ?B7-H4 high.?Emi-Le was observed to be generally well tolerated, with no Grade 4 or 5 treatment-related adverse events (TRAEs) reported.

The most common TRAEs of any grade across the entire patient population were transient aspartate aminotransferase (AST) increase (38% of patients), generally asymptomatic and reversible proteinuria (31%), generally low-grade nausea (29%) and low-grade fatigue (28%). The only Grade 3 TRAEs in =5% or more of all patients were AST increase (14%) and proteinuria (9%). Across the entire enrolled patient population, TRAEs leading to discontinuation, dose reduction and dose delay were observed in 2.3%, 9.2% and 12.3% of patients, respectively.

No dose-limiting treatment-related neutropenia, neuropathy, ocular toxicity, interstitial lung disease or thrombocytopenia were reported, which the company believes differentiates Emi-Le from many other approved and clinical-stage ADCs.At intermediate doses in the trial (38.1 mg/m to 67.4 mg/m), the confirmed objective response rate (ORR) among evaluable patients (those with measurable disease at baseline and at least one post-baseline scan) was 23% (6 of 26 patients) across all B7-H4 high tumors and 23% (3 of 13 patients) with B7-H4 high TNBC, all of whom had previously been treated with at least one topo-1 ADC. In the ASCENT Phase 3 clinical trial of sacituzumab govitecan, a topo-1 ADC, the ORR with standard-of-care single-agent chemotherapy in relapsed/refractory TNBC was approximately 5% with progression free survival of approximately seven weeks. Based on these encouraging Emi-Le data at intermediate doses, Mersana has advanced a dose of 67.4 mg/m every four weeks (Q4W) into an expansion cohort in patients with TNBC who have received one to four prior treatment lines, including at least one prior topo-1 ADC.

At high doses above 76 mg/m, the confirmed ORR among evaluable patients was 22% (2 of 9 patients) across all B7-H4 high tumors. Additionally, 78% (7 of 9 patients) had =30% tumor reduction in target lesions. At these high dose levels, objective responses in multiple evaluable patients with B7-H4 high tumors were not confirmed after protocol-mandated dose delays for proteinuria.

Mersana is implementing proteinuria mitigation efforts and continues to explore higher doses in dose escalation and backfill cohorts to identify a second dose for the expansion portion of the trial. Mersana?s Expected 2025 Milestones and Areas of FocusEmi-Le 1H2025: Continue enrollment in expansion at a dose of 67.4 mg/m Q4W in patients with TNBC who have previously received at least one prior topo-1 ADC 2025: Initiate enrollment in expansion at a second dose in patients with TNBC who have previously received at least one prior topo-1 ADC 2025: Present additional Phase 1 clinical data from dose escalation and backfill cohorts XMT-2056, Mersana?s lead Immunosynthen ADC targeting a novel HER2 epitope 2025: Present initial clinical pharmacodynamic STING activation data Pipeline: Continue to support internal pipeline and existing collaborations with Johnson & Johnson and Merck KGaA, Darmstadt, Germany.