FDA Fast Tracks Emiltatug Ledadotin in Advanced/Metastatic Breast Cancer
The FDA has granted fast track designation to emiltatug ledadotin for advanced or metastatic breast cancer treatment, as supported by new phase 1 data.
- The FDA granted fast track designation to emiltatug ledadotin (Emi-Le; XMT-1660) for patients with advanced or metastatic breast cancer, specifically those with HER2-low or HER2-negative disease, including triple-negative breast cancer (TNBC).
- This designation applies to patients who have received a prior topoisomerase-1 inhibitor antibody-drug conjugate (ADC) and, for hormone-receptor positive patients, those who have either received or are ineligible for endocrine therapy.
- The FDA previously granted fast track designation to emiltatug ledadotin for the treatment of adult patients with advanced or metastatic recurrent TNBC.
The FDA has granted a new fast track designation to emiltatug ledadotin for the treatment of advanced or metastatic breast cancer, specifically targeting patients with HER2-low or HER2-negative disease, including TNBC.1
This designation applies to patients who have previously received a topoisomerase-1 inhibitor antibody-drug conjugate (ADC). Additionally, hormone-receptor positive patients must have either received prior endocrine therapy or be ineligible for such treatment.
The FDA had previously granted fast track designation to emiltatug ledadotin for adult patients with advanced or metastatic recurrent TNBC.
“Topoisomerase-1 inhibitor ADCs are rapidly becoming the standard of care for metastatic TNBC and hormone-receptor positive breast cancer, and an increasing amount of research shows that these patients are exceedingly difficult to treat thereafter,” said Martin Huber, MD, president and chief executive officer of Mersana Therapeutics, in a press release. “This growing population is a primary focus for us as we advance the development of Emi-Le. We are excited to announce this additional fast track designation and the initial clinical data from our ongoing phase 1 clinical trial that were press released separately this morning.”
Breast cancer, female anatomy: © peterschreiber.media - stock.adobe.com
Emiltatug ledadotin targets B7-H4 and has a precise drug-to-antibody ratio, according to Mersana Therapeutics, Inc. Overexpression of B7-H4 is common in many cancers, including breast, endometrial, and ovarian cancer.
According to positive initial clinical data from phase 1 dose-escalation and backfill cohorts for emiltatug ledadotin, the agent was shown to be generally well tolerated with a differentiated safety and tolerability profile and no grade 4 or 5 treatment-related adverse events (TRAEs) reported in patients with TNBC.2
As of a data cutoff date of December 13, 2024, the dose-escalation portion of the phase 1 trial included 130 patients with advanced or metastatic TNBC; HR-positive/HER2-negative breast cancer; ovarian cancer; endometrial cancer and adenoid cystic carcinoma type 1.
Patients were heavily pretreated, with patients receiving up to 15 and a median of 4.5 prior lines of therapy. About 92% of patients with TNBC enrolled in the study had been treated with at least 1 prior topoisomerase-1 inhibitor ADC. Approximately 44% of the 103 patients with known B7-H4 tumor expression had a tumor proportion score of 70% or higher.
At intermediate doses in the trial (38.1 mg/m2 to 67.4 mg/m2), the confirmed objective response rate (ORR) observed among the evaluable patients was 23% across all B7-H4 high tumors and 23% with B7-H4 high TNBC. All of these patients have been previously treated with at least 1 topoisomerase-1 inhibitor.
The most common any-grade TRAEs were transient aspartate aminotransferase increase (38%), generally asymptomatic and reversible proteinuria (31%), generally low-grade nausea (29%), and low-grade fatigue (28%). Grade 3 TRAEs observed in ≥5% or more of all patients were aspartate aminotransferase increase (14%) and proteinuria (9%).
TRAEs led to discontinuation, dose reduction, and dose delay in 2.3%, 9.2%, and 12.3% of the entire enrolled patient population, respectively. Further, there were no dose-limiting treatment-related neutropenia, neuropathy, ocular toxicity, interstitial lung disease, or thrombocytopenia reported in the study.
Based on these findings, a dose of emiltatug ledadotin given at 67.4 mg/m2 every 4 weeks has advanced into an expansion cohort in patients with TNBC who have received 1 to 4 prior treatment lines.
REFERENCES:
Mersana Therapeutics announces additional FDA fast track designation granted to emiltatug ledadotin (XMT-1660). News release. Mersana Therapeutics, Inc. January 10, 2025. Accessed January 13, 2025. https://tinyurl.com/ym66c4h7
Mersana Therapeutics announces positive initial clinical data from phase 1 clinical trial of emiltatug ledadotin (XMT-1660); Initiation of expansion in triple negative breast cancer. News release. Mersana Therapeutics, Inc. January 10, 2025. Accessed January 13, 2025. https://tinyurl.com/59b7f33r
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