Phase III CONTESSA study of tesetaxel meets primary endpoint in metastatic breast cancer.- Odonate Therapeutics

Odonate Therapeutics announced positive results from CONTESSA, a Phase III study of tesetaxel in patients with metastatic breast cancer (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 hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative MBC previously treated with a taxane in the neoadjuvant or adjuvant setting. 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. The ORR as assessed by the IRC was 57% for tesetaxel plus a reduced dose of capecitabine versus 41% for the approved dose of capecitabine alone (p=0.0002). The DCR as assessed by the IRC was 67% for tesetaxel plus a reduced dose of capecitabine versus 50% for the approved dose of capecitabine alone (p<0.0001). while os data are immature, a recent interim analysis indicated the absence of an adverse effect on os with tesetaxel plus a reduced dose of capecitabine. a protocol?specified final analysis of os is expected to occur in 2022. tesetaxel plus capecitabine was associated with a manageable side effect profile consistent with findings from previous clinical studies. grade of at least 3 treatment-emergent adverse events (teaes) that occurred in at least 5% of patients were: neutropenia (70.9% for tesetaxel plus capecitabine vs. 8.3% for capecitabine alone); diarrhea (13.1% 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 (13.1% 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 (9.8% for tesetaxel plus capecitabine vs. 0.9% for capecitabine alone); and anemia (8.0% for tesetaxel plus capecitabine vs. 2.4% for capecitabine alone). adverse events resulting in treatment discontinuation in at least 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); sepsis or septic shock (1.8% for tesetaxel plus capecitabine vs. 0.6% 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). data were presented at the 2020 san antonio breast cancer symposium (sabcs) by joyce o’shaughnessy, m.d., celebrating women chair in breast cancer research, baylor university medical center, texas oncology and chair, breast cancer research, us oncology, and co?principal investigator of contessa.>