Phase 2 basket trial of ado-trastuzumab emtansine for patients with advanced/metastatic HER2-amplified cancers

A phase 2 basket trial at Memorial Sloan Kettering Cancer Center (New York, NY) evaluated the efficacy of ado-trastuzumab emtansine (T-DM1) among patients with advanced/metastatic HER2-amplified solid tumors. The trial included 95 patients in five cohorts: salivary gland, lung, colorectal, endometrial, and ‘other’ cancer. All patients received T-DM1 3.6 mg/kg every 21 days. The primary endpoint was overall response rate (ORR). Among 95 patients, the ORR was 23% (95% CI 16-33). The confirmed ORRs by cohort were salivary: 11 out of 19 (58%; 95% CI 36-77), lung: 4 out of 23 (17%; 7-37), colorectal: 0 out of 7 (0%; 0-35), endometrial: 5 out of 23 (22%; 10-42), and ‘other’: 2 out of 23 (9%; 2-27). Median progression-free survival was 3.6 months (95% CI 2.6-5.4), and ranged for 1.4 months in the ‘other’ cohort to 10.2 months in the salivary cohort. Median overall survival was 11.9 months (95% CI 8.4-17.2) and ranged for 7.8 months in the ‘other’ cohort to 29.2 months in the salivary cohort. Median duration of response was 13.1 months (95% CI 7.3-30.5), and ranged from 6.4 months in the lung cohort to 18.4 months in the ‘other’ cohort. The authors conclude that T-DM1 demonstrated heterogeneous efficacy among HER2-amplified tumor types, with promising responses and outcomes among patients with salivary gland cancer.