News
Article
FDA Grants Additional Fast Track Designation to Emiltatug Ledadotin to Treat HER2 Low, HER2-Negative Breast Cancer
Author(s):
Key Takeaways
- Emiltatug ledadotin (emi-le) received FDA fast track designation for advanced/metastatic breast cancer, including HER2-low/negative and TNBC, after positive phase 1 trial results.
- Phase 1 trial showed a 23% objective response rate in heavily pre-treated patients, with no grade 4 or 5 treatment-related adverse events, indicating good tolerability.
A new indication for the antibody-drug conjugate expands the future clinical potential of the treatment in patients with the rare breast cancer.
The FDA announced a new fast track designation (FTD) for emiltatug ledadotin (emi-le, XMT-1660; Mersana Therapeutics) for the treatment of advanced or metastatic breast cancer in patients with human epidermal growth factor receptor 2 (HER2) low (IHC 1+ or IHC 2+/ISH–) or HER2-negative (IHC 0) disease—including triple-negative breast cancer (TNBC)—who have received a prior topoisomerase-1 inhibitor antibody-drug conjugate (ADC), according to a news release from Mersana Therapeutics.1
Emiltatug ledadotin could become an effective, newly-approved treatment option for patients with HER2 low or HER2-negative breast cancer. | Image Credit: © Chutima | stock.adobe.com
The additional designation comes on the heels of positive data from a phase 1 clinical trial (NCT05377996) of emi-le that enrolled 130 patients that were heavily pre-treated. In the trial, the objective response rate (ORR) among evaluable patients who received intermediate doses was 23% across all patients with B7-H4 tumors and a tumor expression score of 70% or higher, and 23% with B7-H4 high TNBC. These patients had all been previously treated with at least 1 topoisomerase (topo)-1-ADC.2,3
Widespread tolerability was reported across the patient population, with no grade 4 or 5 treatment-related adverse events (TRAEs) reported, an important marker of emi-le’s safety. Common TRAEs that were reported across the patient population were transient aspartate aminotransferase (AST) increase (38%), proteinuria that was generally asymptomatic (9%), nausea (29%), and fatigue (28%).2
These results can be compared with those from the phase 3 ASCENT clinical trial, which examined another topo-1 ADC, sacituzumab govitecan, in relapsed/refractory TNBC. In that trial, patients demonstrated an ORR of 5% with progression-free survival of 7 weeks, significantly lower than emi-le in the previously mentioned phase 1 trial. Thus, investigators are optimistic regarding emi-le’s efficacy and safety.2
Emi-le was also investigated at high doses, in which the confirmed ORR among evaluable patients was 22% across all B7-H4 high tumors. Furthermore, 78% had 30% or higher tumor reduction in target lesions. Key investigators, including Erika Hamilton, MD, director of breast cancer research at Sarah Cannon Research Institute, note the positive efficacy data and that all patients were previously treated with a topo-1 ADC.2
“In terms of both tolerability and clinical activity, these emi-le data are encouraging,” Hamilton said in a news release “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.”2
Previously, the FDA granted FTD to emi-le for the treatment of adults with advanced or metastatic recurrent TNBC. The new indication expands the development opportunities for emi-le and could allow treatment providers and pharmacists to eventually have another treatment option for patients with the difficult-to-manage disease. FTD allows for emi-le to be eligible for several benefits, such as more frequent communication with the FDA and the possibility of accelerated approval by the agency.1
B7-H4, a plasma membrane protein, is expressed in multiple forms of tumors, including breast cancer. Studies have found that its expression in tumors is associated with a lower frequency of tumor-infiltrating immune cells. One model found that knocking out the protein was associated with reduced metastasis, heightened antitumor immune response, and increased survival. Importantly, ADCs such as emi-le have been shown in preclinical trials to make B7-H4 amenable to an immune response.4
“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,” Martin Huber, MD, president and chief executive officer of Mersana Therapeutics, said in a news release. “This growing population is a primary focus for us as we advance the development of emi-le.”1
