Mersana Therapeutics reports positive phase 1 data for novel ADC in triple-negative breast cancer

Mersana Therapeutics, Inc., a clinical-stage biopharmaceutical innovator, has announced promising early clinical data from its Phase 1 trial evaluating emiltatug ledadotin (Emi-Le; XMT-1660), an antibody-drug conjugate (ADC) targeting B7-H4. The trial, which enrolled patients with various advanced or metastatic cancers, has shown potential in addressing the unmet needs of individuals with triple-negative breast cancer (TNBC).

The preliminary findings highlight Emi-Le’s differentiated safety profile, tolerability, and clinical activity, particularly in patients with TNBC who had previously received at least one topo-1 ADC. These results position Emi-Le as a potential game-changer in cancer care, especially for those who have exhausted conventional treatment options.

Unveiling Promising Results from Phase 1 Clinical Trial

The Phase 1 trial of Emi-Le, part of Mersana’s Dolasynthen ADC platform, enrolled 130 patients with advanced TNBC, hormone receptor-positive breast cancer, ovarian cancer, and other solid tumors. These patients, many of whom had undergone multiple prior therapies, represent a cohort with significant unmet clinical needs.

Of the 103 participants with known B7-H4 tumor expression, approximately 44% were identified as having a “B7-H4 high” tumor proportion score of 70% or higher. Emi-Le demonstrated notable tolerability across this population, with no Grade 4 or 5 treatment-related adverse events reported. Common side effects, such as low-grade proteinuria and fatigue, were manageable, reinforcing the safety profile of this ADC.

Clinical activity was evident, particularly among patients with high B7-H4 expression. At intermediate doses of 38.1 mg/m² to 67.4 mg/m², the confirmed objective response rate (ORR) was 23% across all B7-H4 high tumors, including TNBC cases. Importantly, tumor reduction was observed in 78% of patients treated at higher doses, signaling the potential for significant efficacy.

Advancing ADC Innovation in Breast Cancer

The data from this trial underscore the role of ADCs in redefining cancer treatment, particularly for TNBC—a subtype marked by aggressive progression and limited treatment options. In comparison to existing therapies, such as sacituzumab govitecan, which showed an ORR of approximately 5% in similar TNBC populations, Emi-Le’s performance suggests a meaningful advancement.

Martin Huber, M.D., President and CEO of Mersana Therapeutics, emphasized that the early findings validate Emi-Le’s potential to address a high unmet need. He highlighted the encouraging safety and efficacy data as a foundation for expanding research in TNBC and other tumor types.

Experts in oncology, such as Dr. Erika Hamilton from the Sarah Cannon Research Institute, have also expressed optimism. Dr. Hamilton noted that the ability of Emi-Le to elicit responses in heavily pretreated TNBC patients is particularly significant, given the limited options available for those previously treated with topo-1 ADCs.

Expanding Research Efforts in 2025

Building on these promising results, Mersana has initiated an expansion cohort for Emi-Le at a dose of 67.4 mg/m² in TNBC patients who have received at least one prior topo-1 ADC. The company is also exploring strategies to mitigate side effects, such as proteinuria, to optimize outcomes further.

In addition to Emi-Le, Mersana’s pipeline includes XMT-2056, an Immunosynthen ADC targeting HER2. This candidate, expected to deliver initial pharmacodynamic data in 2025, exemplifies the company’s commitment to leveraging ADC technology for innovative cancer therapies.

Mersana’s collaborations with leading biopharmaceutical companies, including Johnson & Johnson and Merck KGaA, Darmstadt, Germany, further bolster its research initiatives. These partnerships aim to accelerate the development of ADCs that address a wide spectrum of cancers, broadening the impact of this technology in oncology.

Addressing Unmet Needs in Triple-Negative Breast Cancer

Triple-negative breast cancer remains one of the most challenging subtypes to treat, with limited targeted therapies and high recurrence rates. The ability of Emi-Le to induce responses in patients who have previously undergone multiple treatment lines, including topo-1 ADCs, underscores its potential to fill a critical gap in the oncology landscape.

Mersana’s strategic focus on B7-H4, a target overexpressed in several tumors, reflects its dedication to addressing cancers with significant clinical need. By combining precision targeting with an innovative payload delivery system, Emi-Le aims to provide new hope for patients with advanced TNBC and beyond.

A Look Ahead

As Mersana Therapeutics moves into 2025, its robust pipeline and groundbreaking ADC technology continue to attract attention from the oncology community. With plans to present additional Phase 1 data and expand its research into higher doses, the company is poised to make significant strides in cancer treatment.

For patients with TNBC and other high-risk cancers, Mersana’s advancements signal a future where precision medicine and innovative ADCs offer renewed hope. As clinical trials progress, the oncology field eagerly awaits further insights into Emi-Le’s impact and its potential to reshape cancer care.