Final Overall Survival Results of Datopotamab Deruxtecan in Metastatic HR Positive, HER2 Low/Negative Breast Cancer from TROPION-Breast01 Phase 3 Trial

TOKYO, Japan & BASKING RIDGE, NJ, USA I September 23, 2024 I

Topline results from the TROPION-Breast01 phase 3 trial of datopotamab deruxtecan (Dato-DXd) compared to investigator’s choice of chemotherapy have been shared. The study previously met one of its primary endpoints, progression-free survival (PFS), but did not achieve statistical significance in the final analysis for overall survival (OS) in patients with inoperable or metastatic hormone receptor (HR) positive, HER2 low or negative breast cancer who had been treated with endocrine-based therapy and at least one systemic therapy.

Datopotamab deruxtecan is a TROP2-directed DXd antibody drug conjugate (ADC) created by Daiichi Sankyo and is being developed in partnership with AstraZeneca. Earlier, the 2023 European Society for Medical Oncology Congress highlighted the statistically significant improvement in PFS with datopotamab deruxtecan. These results were published in the Journal of Clinical Oncology, which also noted improvements in patient-reported outcomes.

The safety profile of datopotamab deruxtecan remained consistent with previous findings, showing lower rates of grade 3 or higher treatment-related adverse events compared to chemotherapy and no new safety concerns. Rates of interstitial lung disease (ILD) events remained low, with no new grade 3 or higher ILD cases.

The introduction of other ADCs such as ENHERTU® (trastuzumab deruxtecan) during the trial may have influenced survival outcomes. Despite not achieving the OS endpoint, the progression-free survival benefit of datopotamab deruxtecan in TROPION-Breast01 underscores its potential clinical value, as noted by Ken Takeshita, MD, Global Head of R&D at Daiichi Sankyo, and Susan Galbraith, PhD, Executive Vice President of Oncology R&D at AstraZeneca.

The data from the trial will be presented at an upcoming medical meeting and shared with regulatory authorities. In addition to TROPION-Breast01, Daiichi Sankyo and AstraZeneca are actively investigating datopotamab deruxtecan in other clinical trials, such as TROPION-Breast02, TROPION-Breast03, TROPION-Breast04, and TROPION-Breast05, focusing on various subtypes of breast cancer.

TROPION-Breast01 is a global, randomized, multicenter, open-label phase 3 trial evaluating datopotamab deruxtecan against single-agent chemotherapy (options including eribulin, capecitabine, vinorelbine, or gemcitabine) in adults with unresectable or metastatic HR positive, HER2 low or negative breast cancer unresponsive to endocrine therapy and at least one systemic therapy. Over 700 patients participated in the trial, which measured PFS and OS as primary endpoints, along with secondary endpoints such as objective response rate, duration of response, disease control rate, and safety.

Breast cancer remains the second most common cancer globally and a leading cause of cancer-related deaths. In 2022, more than two million cases were diagnosed, with over 665,000 deaths. Early-stage breast cancer has high survival rates, but metastatic disease remains challenging, with less than 35% of patients expected to live five years post-diagnosis. Hormone receptor-positive breast cancer represents approximately 70% of cases and is often treated with endocrine therapies, although their efficacy diminishes after two lines of treatment, leading to chemotherapy as the next line of treatment despite its limited effectiveness.

Datopotamab deruxtecan is designed using Daiichi Sankyo’s proprietary DXd ADC Technology and is part of a comprehensive global clinical development program with over 20 trials targeting various cancers, including non-small cell lung cancer and multiple subtypes of breast cancer.

The collaboration between Daiichi Sankyo and AstraZeneca began in March 2019 for ENHERTU and extended in July 2020 to include datopotamab deruxtecan. Daiichi Sankyo oversees the manufacturing and supply of both ADCs.