AstraZeneca and Daiichi Sankyo have dosed the first patient in their DESTINY-Endometrial01 Phase 3 trial, evaluating ENHERTU® (trastuzumab deruxtecan) as a first-line endometrial therapy for patients with HER2-expressing primary advanced or recurrent endometrial cancer. This strategic trial initiation represents a significant expansion of ENHERTU’s clinical development program beyond its established breast cancer indications.
The antibody-drug conjugate’s entry into first-line endometrial therapy builds on compelling Phase 2 data from the DESTINY-PanTumor02 trial, where trastuzumab deruxtecan demonstrated clinically meaningful responses across multiple HER2-expressing solid tumors, including gynecological cancers. The scientific rationale centers on targeting HER2 overexpression, which occurs in approximately 20-30% of endometrial cancers and correlates with aggressive disease characteristics.
ENHERTU’s expansion into first-line endometrial therapy addresses a substantial unmet medical need in gynecological oncology. Current standard-of-care options for advanced endometrial cancer remain limited, particularly for HER2-positive disease. The FDA has previously granted ENHERTU breakthrough therapy designations across multiple tumor types, establishing a favorable regulatory pathway for future submissions.
The trial’s design will likely evaluate progression-free survival as the primary endpoint, consistent with ENHERTU’s successful Phase 3 programs in breast cancer. This approach aligns with FDA guidance for oncology drug development and supports potential accelerated approval pathways.
“The initiation of DESTINY-Endometrial01 represents our commitment to extending ENHERTU’s transformative potential to patients with gynecological cancers,” said Ken Takeshita, Global Head of R&D at Daiichi Sankyo, reflecting the company’s broader pan-tumor strategy.
The endometrial cancer market represents a significant commercial opportunity, with global incidence rates rising due to demographic trends and metabolic syndrome prevalence. ENHERTU’s potential entry as a first-line endometrial therapy could capture substantial market share in the HER2-positive segment, complementing its expanding breast cancer franchise.
Key trial milestones will include interim safety assessments and planned efficacy analyses, with topline results anticipated by 2027-2028. Success in this indication would strengthen ENHERTU’s position as a leading pan-tumor ADC platform and support premium pricing strategies across gynecological oncology.
The DESTINY-Endometrial01 trial launch underscores the evolving paradigm toward precision medicine in gynecological cancers, positioning ENHERTU as a cornerstone therapy for HER2-directed treatment strategies across multiple tumor types.
