Daiichi Sankyo Initiates Phase 3 TROPION-Breast01 Trial of TROP2-Targeted ADC Datopotamab Deruxtecan in HR+/HER2- Metastatic Breast Cancer

News on November 20, 2021 /BioValleyBIOON/ -- Daiichi Sankyo recently announced that the first patient has been dosed in the global TROPION-Breast01 Phase 3 trial. The trial is for HR+/HER2-, inoperable or metastatic patients who have previously received chemotherapy.Breast CancerThe efficacy and safety of datopotamab deruxtecan (Dato-DXd; DS-1062) are being evaluated in patients.Datopotamab deruxtecan is a TROP2-targeted antibody-drug conjugate (ADC) developed by Daiichi Sankyo andAstraZenecaCo-development.

Breast cancer is the most common cancer globally, with over 2 million confirmed cases and nearly 685,000 deaths in 2020. Approximately 70% of breast cancers are considered HR+/HER2-. For patients with HR+/HER2- metastatic breast cancer whose disease progresses during hormone therapy or who are unsuitable for such regimens, the current standard of care is single-agent chemotherapy, with the effectiveness of each subsequent treatment diminishing.

Senior Vice President of Daiichi Sankyo Company LimitedTumorGlobal R&D Head Gilles Gallant stated, "Currently, there are no approved TROP2-targeted therapies for HR+/HER2- breast cancer. We are encouraged by the clinical profile datopotamab deruxtecan has demonstrated in patients with breast cancer. TROPION-Breast01 is the first pivotal trial of datopotamab deruxtecan in breast cancer and the third pivotal study in our clinical development program, underscoring our efforts to accelerate the development of TROP2-directed ADCs in breast and lung cancers."

TROP2 (trophoblast cell surface antigen 2) is a transmembrane glycoprotein that is overexpressed in a variety of solid tumors, including breast cancer. Studies have shown that high expression of TROP2 is associated with cancer cell growth and proliferation, as well as low patient survival rates. Although TROP2 is expressed in all subtypes of breast cancer, it is overexpressed in approximately 80% of TNBC patients, making it a very promising molecular target for the development of new drugs.

In March 2019, AstraZeneca and Daiichi Sankyo signed an immunotherapy agreement worth up to $6.9 billion.TumorCollaborate to jointly develop the HER2-targeted ADC therapy Enhertu (trastuzumab deruxtecan, DS-8201) for the treatment of various cancer patients with different levels of HER2 expression or HER2 mutations, including gastric cancer, colorectal cancer, lung cancer, and breast cancer with low HER2 expression.

In July 2020, the two parties signed another immunization agreement worth up to 6 billion US dollars.TumorCollaborate in the development of datopotamab deruxtecan (DS-1062), an ADC therapy targeting TROP2, which is currently in Phase I clinical trials for the treatment of non-small cell lung cancer (NSCLC) and triple-negative breast cancer (TNBC).

In August 2020, the two parties entered into aClinical TrialCollaboration to Evaluate Patritumab Deruxtecan (U3-1402) in Combination with Tagrisso (Osimertinib) for the Treatment of Patients with EGFR-Mutated Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC).

Enhertu, datopotamab deruxtecan, and patritumab deruxtecan are all next-generation ADC drugs developed by Daiichi-Sankyo using DXd ADC technology., through a 4-peptide linker targetingTumorHumanized monoclonal antibodies targeting specific cell surface antigens (namely: anti-HER2 monoclonal antibody [Trastuzumab], anti-TROP2 monoclonal antibody, and anti-HER3 monoclonal antibody [Patritumab]) are linked to a novel topoisomerase 1 inhibitor Exatecan derivative (DX-8951 derivative, DXd), enabling targeted delivery of cytotoxic agents into cancer cells. Compared with conventional chemotherapy, this approach can reduce systemic exposure to cytotoxic agents.

To date, Enhertu has been approved for the treatment of two types of cancer: (1) for adult patients with unresectable or metastatic HER2-positive breast cancer who have previously received at least two HER2-based regimens; (2) for the treatment of patients with HER2-positive unresectable advanced or recurrent gastric cancer. (Bioon.com)

Source of the original text:TROPION-Breast01 Phase 3 Trial of Datopotamab Deruxtecan Initiated in Patients with Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer