On January 10, 2025 Mersana Therapeutics, Inc. (NASDAQ: MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported 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 (Press release, Mersana Therapeutics, JAN 10, 2025, View Source [SID1234649594]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"We believe the initial safety, tolerability and efficacy data for Emi-Le demonstrate a profile that is exciting and differentiated within both the B7-H4 field and the broader ADC landscape," said Martin Huber, M.D., President and Chief Executive Officer of Mersana Therapeutics. "We have observed clinical activity across tumors, including in heavily pre-treated patients with TNBC. These clinical data have led us to initiate expansion in patients with TNBC who have previously been treated with at least one topo-1 ADC, a population with very high unmet need."
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/m2 to 67.4 mg/m2), 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/m2 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.
"In terms of both tolerability and clinical activity, these Emi-Le data are encouraging," Erika Hamilton, M.D., Director Breast Cancer Research, Sarah Cannon Research Institute in Nashville, Tennessee, said, "It is notable that all the TNBC patients who responded to Emi-Le had previously been treated with at least one topo-1 ADC. The results indicate that Emi-Le may help address an already substantial and growing need among topo-1 experienced breast cancer patients for new treatments."
At high doses above 76 mg/m2, 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 Focus
Emi-Le
· 1H2025: Continue enrollment in expansion at a dose of 67.4 mg/m2 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
Conference Call Information
Mersana will host a conference call today at 8:30 a.m. ET to discuss the initial clinical data from its Phase 1 clinical trial of Emi-Le. To access the call, please dial 833-255-2826 (domestic) or 412-317-0689 (international). A live webcast that includes the data presentation will be available on the Investors & Media section of the Mersana website at www.mersana.com, and a replay of the webcast will be available in the same location following the conference call for approximately 90 days.