Odonate Therapeutics announces positive top line results from CONTESSA, a phase III study of tesetaxel in patients with metastatic breast cancer.

Odonate Therapeutics, Inc. announced positive top-line results from CONTESSA, a Phase III study of tesetaxel in patients with metastatic breast cancer (MBC). CONTESSA is a multinational, multicenter, randomized, Phase III study of tesetaxel, an investigational, orally administered taxane, in patients with MBC. CONTESSA is comparing tesetaxel dosed orally at 27 mg/m2 on the first day of each 21 day cycle plus a reduced dose of capecitabine (1,650 mg/m2/day dosed orally for 14 days of each 21 day cycle) to the approved dose of capecitabine alone (2,500 mg/m2/day dosed orally for 14 days of each 21 day cycle) in 685 patients randomized 1:1 with human epidermal growth factor receptor 2 (HER2) negative, hormone receptor (HR) positive MBC previously treated with a taxane in the neoadjuvant or adjuvant setting. Capecitabine is an oral chemotherapy agent that is considered a standard of care treatment in MBC. Where indicated, patients must have received endocrine therapy with or without a cyclin dependent kinase (CDK) 4/6 inhibitor. The primary endpoint is progression?free survival (PFS) as assessed by the Independent Radiologic Review Committee (IRC). The secondary efficacy endpoints are overall survival (OS), objective response rate (ORR) as assessed by the IRC and disease control rate (DCR) as assessed by the IRC. CONTESSA is being conducted at 180 investigational sites in 18 countries in North America, Europe and Asia.CONTESSA met the primary endpoint of improved PFS as assessed by the IRC. Median PFS was 9.8 months for tesetaxel plus a reduced dose of capecitabine versus 6.9 months for the approved dose of capecitabine alone, an improvement of 2.9 months. The risk of disease progression or death was reduced by 28.4% [hazard ratio=0.716 (95% confidence interval: 0.573-0.895); p=0.003] for tesetaxel plus a reduced dose of capecitabine versus the approved dose of capecitabine alone. Tesetaxel plus capecitabine was associated with a manageable side effect profile consistent with findings from previous clinical studies. Grade greater than 3 treatment-emergent adverse events (TEAEs) that occurred in greater than 5% of patients were: neutropenia (71.2% for tesetaxel plus capecitabine vs. 8.3% for capecitabine alone); diarrhea (13.4% for tesetaxel plus capecitabine vs. 8.9% for capecitabine alone); hand foot syndrome (6.8% for tesetaxel plus capecitabine vs. 12.2% for capecitabine alone); febrile neutropenia (12.8% for tesetaxel plus capecitabine vs. 1.2% for capecitabine alone); fatigue (8.6% for tesetaxel plus capecitabine vs. 4.5% for capecitabine alone); hypokalemia (8.6% for tesetaxel plus capecitabine vs. 2.7% for capecitabine alone); leukopenia (10.1% for tesetaxel plus capecitabine vs. 0.9% for capecitabine alone); and anemia (8.0% for tesetaxel plus capecitabine vs. 2.1% for capecitabine alone). Adverse events resulting in treatment discontinuation> in greater than 1% of patients were: neutropenia or febrile neutropenia (4.2% for tesetaxel plus capecitabine vs. 1.5% for capecitabine alone); neuropathy (3.6% for tesetaxel plus capecitabine vs. 0.3% for capecitabine alone); diarrhea (0.9% for tesetaxel plus capecitabine vs. 1.5% for capecitabine alone); and hand foot syndrome (0.6% for tesetaxel plus capecitabine vs. 2.1% for capecitabine alone). Treatment discontinuation due to any adverse event occurred in 23.1% of patients treated with tesetaxel plus capecitabine versus 11.9% of patients treated with capecitabine alone. Grade 2 alopecia (hair loss) occurred in 8.0% of patients treated with tesetaxel plus capecitabine versus 0.3% of patients treated with capecitabine alone. Grade 3 neuropathy occurred in 5.9% of patients treated with tesetaxel plus capecitabine versus 0.9% of patients treated with capecitabine alone. While overall survival (OS) data are not mature, a recent interim analysis indicated the absence of an adverse effect on OS. A final analysis of OS is expected to occur in 2022. “The clinically meaningful PFS improvement observed in CONTESSA, along with once every three week oral dosing and low rates of clinically significant hair loss and neuropathy, could make tesetaxel an important new treatment option for patients with metastatic breast cancer,” said Andrew Seidman, M.D., Attending Physician, Breast Medicine Service, Department of Medicine, Medical Director, Bobst International Center, Memorial Sloan Kettering Cancer Center and Professor of Medicine, Weill Cornell Medical College, and Co Principal Investigator of CONTESSA. Comment:While the trial met the primary endpoint of improved Progression Free Survival (PFS) with median PFS of 9.8 months for tesetaxel plus a reduced dose of capecitabine vs 6.9 months for the approved dose of capecitabine alone, the improvement of 2.9 months was below expectations. The data also showed side effects, with cases of neutropenia, a cause for a previous clinical hold, recorded at 71.2% for tesetaxel plus capecitabine vs 8.3% for capecitabine alone.