Abstract OT1-07-04: [Fam-] trastuzumab deruxtecan (T-DXd; DS-8201a) vs investigator’s choice of treatment in subjects with HER2-positive, unresectable and/or metastatic breast cancer who previously received T-DM1: A randomized, phase 3 trial (DESTINY-Breast02)
Authors: André Fabrice , Shahidi Javad , Lee Caleb , Wang Kongming , Krop Ian E 
Published: March 2020

Abstract
Background: There is no uniform standard of care for HER2-positive breast cancer (BC) after disease progression on ado-trastuzumab emtansine (T-DM1). [Fam-] trastuzumab deruxtecan (T-DXd; formerly DS-8201a) is a novel HER2-targeted antibody-drug conjugate (ADC) with a humanized HER2 antibody attached to a topoisomerase I inhibitor payload by a cleavable tetrapeptide-based linker and a drug-to-antibody ratio of 7 to 8. It was designed with the goal of improving critical attributes of an ADC. In a phase 1 study, T-DXd showed promising antitumor activity in subjects with HER2-positive BC previously treated with T-DM1 with a confirmed objective response rate (ORR) of 59.5% (Tamura et al, Lancet Oncol, 2019). Results from the pivotal, phase 2 study of subjects with HER2-positive BC previously treated with T-DM1 (DESTINY-Breast01) confirmed the activity observed in the phase 1 study and will be presented at the meeting (Krop, et al). Here, we describe the phase 3 confirmatory trial evaluating T-DXd in subjects with HER2-positive, unresectable and/or metastatic breast cancer who previously received T-DM1. Study Description: DESTINY-Breast02 is a multicenter, open-label, phase 3 trial that is comparing the efficacy and safety of T-DXd with those of the investigator’s choice of therapy in subjects with centrally confirmed, HER2-positive (IHC 3+ or ISH+), unresectable and/or metastatic BC that progressed on or after T-DM1. The trial started in August 2018 and is recruiting subjects from ≈ 190 sites in North and South America, Europe, and Asia. Approximately 600 subjects will be randomized (2:1) to T-DXd or the investigator’s choice of treatment (trastuzumab + capecitabine or lapatinib + capecitabine). Randomization is stratified by hormone receptor status, prior pertuzumab treatment, and history of visceral disease. T-DXd (5.4 mg/kg) will be administered intravenously once every 3 weeks. Progression-free survival (PFS) based on blinded, independent central review using RECIST v1.1 criteria is the primary efficacy endpoint; overall survival (OS) is the key secondary endpoint. Other secondary efficacy endpoints are ORR, duration of response, and PFS based on investigator assessment. Safety assessments include serious and treatment-emergent adverse events, physical examinations, vital signs, and clinical laboratory parameters. Health-related quality of life will also be measured. Long-term follow-up will continue after the primary analysis every 3 months until death, withdrawal of consent, loss to follow-up, or trial closure. Efficacy analyses will include all randomized subjects, and safety analyses will include all randomized subjects who received ≥ 1 dose of trial treatment. For further information on this trial, visit ClinicalTrials.gov (NCT03523585).
Citation Format: Fabrice André, Javad Shahidi, Caleb Lee, Kongming Wang, Ian E Krop. [Fam-] trastuzumab deruxtecan (T-DXd; DS-8201a) vs investigator’s choice of treatment in subjects with HER2-positive, unresectable and/or metastatic breast cancer who previously received T-DM1: A randomized, phase 3 trial (DESTINY-Breast02) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-07-04.