Trastuzumab deruxtecan achieved a tumour response rate of 60.9% in pivotal phase II HER2-positive metastatic breast cancer trial (DESTINY-Breast01).- Daiichi Sankyo + AstraZeneca

Daiichi Sankyo presented positive detailed data from the global pivotal phase II single-arm DESTINY-Breast01 trial of DS-8201 ([fam-] trastuzumab deruxtecan), an investigational HER2 targeting antibody drug conjugate (ADC), in patients with HER2 positive metastatic breast cancer.

The primary endpoint of objective response rate (ORR), confirmed by independent central review, was 60.9% with DS-8201 monotherapy (5.4mg/kg) in patients with HER2 positive metastatic breast cancer who received two or more prior HER2 targeted regimens. Patients achieved a disease control rate (DCR) of 97.3% with a median duration of response (DOR) of 14.8 months (range 13.8 - 16.9) and median progression-free survival of 16.4 months (range 12.7 - not reached). The median overall survival (OS) has not yet been reached with an estimated survival rate for patients receiving DS-8201 of 86% at one year. The results were consistent across subgroups of patients.

Patients receiving DS-8201 in the DESTINY-Breast01 trial had a median of six prior regimens for metastatic disease (range 2 - 27), including ado-trastuzumab emtansine (T-DM1) (100%), trastuzumab (100%), pertuzumab (65.8%), other anti-HER2 therapies (54.3%), hormone therapies (48.9%), and other systemic therapies (99.5%). Median treatment duration for DS-8201 was 10 months (range: 0.7 - 20.5 months) with a median duration of follow-up of 11.1 months (range: 0.7 - 19.9). As of data cut-off on August 1, 2019, 42.9% of patients remained on-treatment.

The safety and tolerability profile of DS-8201 in DESTINY-Breast01 was consistent with that observed in the phase 1 trial. The most common grade 3 or higher treatment emergent adverse events were decreased neutrophil count (20.7%), anemia (8.7%), nausea (7.6%), decreased white blood cell count (6.5%), decreased lymphocyte count (6.5%) and fatigue (6%). Overall, 13.6% of patients had confirmed interstitial lung disease (ILD) related to treatment as determined by an independent review. The events were primarily grade 1 or 2 (10.9%) in severity with one grade 3 (0.5%) and no grade 4 events. Four deaths (2.2%) were determined to be due to ILD. The data were part of the press program at the 2019 San Antonio Breast Cancer Symposium (#SABCS19) and simultaneously published online in The New England Journal of Medicine.

See- "Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer." Shanu Modi et al. NEJM December 11, 2019 DOI: 10.1056/NEJMoa1914510