Sacituzumab govitecan-hziy

The FDA on Friday approved datopotamab deruxtecan, an antibody-drug conjugate developed by AstraZeneca and Daiichi Sankyo, for a subset of patients with the most common form of breast cancer, despite mixed clinical trial outcomes. Branded as Datroway, the TROP2-directed antibody-drug conjugate was approved for adults with unresectable or metastatic HR-positive/HER2-negative breast cancer after chemotherapy and hormone therapy. The newly approved treatment will compete with Gilead’s Trodelvy, a TROP2-directed ADC that was approved in a similar setting in 2023. Daiichi Sankyo told Endpoints News via email the list price for Datroway in the US is $4,891.07 per 100 mg vial, which comes out to a monthly list price of around $28,259.52 at the recommended dose of 6 mg/kg once every three weeks. Datroway was first approved for breast cancer in Japan in December. The drug faced some uncertainty around its pending approval when Daiichi Sankyo and AstraZeneca disclosed in September that, in its pivotal study, the treatment failed to prolong survival , a metric many physicians consider to be the gold standard. In the study, known as TROPION-Breast01, the survival outcomes between the two study arms were almost identical. Patients who received Datroway had a median overall survival of 18.6 months compared to 18.3 months for those in the chemotherapy arm. However, the antibody-drug conjugate met the other primary endpoint of progression-free survival in the study — the drug extended progression-free survival by two months compared to the chemotherapy arm. AstraZeneca and Daiichi Sankyo are also seeking approval of datopotamab deruxtecan, known more commonly as dato-dxd, in lung cancer. In November, the companies announced they had withdrawn an application for approval for dato-dxd in advanced nonsquamous non-small cell lung cancer, replacing it with a new application in a smaller population of patients with advanced EGFR-mutated non-small cell lung cancer.

– Emiltatug ledadotin observed to be generally well tolerated with differentiated safety and tolerability profile – Promising clinical activity observed in patients with triple-negative breast cancer (TNBC) previously treated with topoisomerase-1 inhibitor (topo-1) ADCs; confirmed responses observed across all enrolled tumor types – First expansion cohort initiated in patients with TNBC previously treated with at least one topo-1 ADC; dose exploration efforts ongoing – Company announces expected 2025 milestones and areas of focus CAMBRIDGE, MA, USA I January 10, 2025 I 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, today 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. “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/m 2 to 67.4 mg/m 2 ), 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 2 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/m 2 , 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 XMT-2056, Mersana’s lead Immunosynthen ADC targeting a novel HER2 epitope Pipeline 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. About Mersana Therapeutics Mersana Therapeutics is a clinical-stage biopharmaceutical company focused on the development of novel antibody-drug conjugates (ADCs) and driven by the knowledge that patients are waiting for new treatment options. The company has developed proprietary cytotoxic (Dolasynthen) and immunostimulatory (Immunosynthen) ADC platforms that are generating a pipeline of wholly-owned and partnered product candidates with the potential to treat a range of cancers. Its pipeline includes Emi-Le (emiltatug ledadotin; XMT-1660), a Dolasynthen ADC targeting B7-H4, and XMT-2056, an Immunosynthen ADC targeting a novel epitope of human epidermal growth factor receptor 2 (HER2). Mersana routinely posts information that may be useful to investors on the “Investors & Media” section of its website at www.mersana.com . SOURCE: Mersana Therapeutics