Therapy Areas: Central Nervous System
Tesetaxel Brain Concentrations Exceeded Concentrations Required for Tumor Killing for Sustained Period of Time in Preclinical Testing, According to Odonate Therapeutics
4 April 2019 - - US-based pharmaceutical company Odonate Therapeutics, Inc. (NASDAQ: ODT) presented results of preclinical studies of tesetaxel, Odonate's investigational, orally administered taxane, at the American Association for Cancer Research annual meeting 2019, the company said.

The presentation is entitled, "Tesetaxel, a novel, oral taxane, crosses intact blood-brain barrier at therapeutically relevant concentrations" (Poster Board #12; Abstract 3087).

These preclinical results indicate that, following oral administration, tesetaxel achieves brain concentrations that exceed concentrations required for tumor killing for a sustained period of time.

This is in contrast to paclitaxel and docetaxel, the most commonly prescribed taxanes, which do not substantially cross the BBB.

Tesetaxel is an investigational, orally administered chemotherapy agent that belongs to a class of drugs known as taxanes, which are widely used in the treatment of cancer.

Tesetaxel has several pharmacologic properties that make it unique among taxanes, including: oral administration with a low pill burden; a long (~8-day) terminal plasma half-life in humans, enabling the maintenance of adequate drug levels with relatively infrequent dosing; no history of hypersensitivity (allergic) reactions; and significant activity against chemotherapy-resistant tumors.

In patients with metastatic breast cancer, tesetaxel was shown to have significant, single-agent antitumor activity in two multicenter, Phase 2 studies.

CONTESSA is a multinational, multicenter, randomized, Phase 3 study of tesetaxel, an investigational, orally administered taxane, in patients with locally advanced or metastatic breast cancer (LA/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 approximately 600 patients randomized 1: 1 with human epidermal growth factor receptor 2 negative, hormone receptor positive LA/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 LA/MBC. Where indicated, patients must have received endocrine therapy with or without a cyclin-dependent kinase 4/6 inhibitor.

The primary endpoint is progression-free survival as assessed by an Independent Radiologic Review Committee.

CONTESSA's secondary efficacy endpoints are overall survival, objective response rate as assessed by the IRC and disease control rate as assessed by the IRC.

CONTESSA 2 is a multinational, multicenter, Phase 2 study of tesetaxel, an investigational, orally administered taxane, in patients with locally advanced or metastatic breast cancer (LA/MBC).

CONTESSA 2 is investigating 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) in approximately 125 patients with human epidermal growth factor receptor 2 negative, hormone receptor positive LA/MBC not previously treated with a taxane.

Capecitabine is an oral chemotherapy agent that is considered a standard-of-care treatment in LA/MBC. Where indicated, patients must have received endocrine therapy with or without a cyclin-dependent kinase 4/6 inhibitor.

The primary endpoint is objective response rate as assessed by an Independent Radiologic Review Committee. The secondary efficacy endpoints are duration of response as assessed by the IRC, progression-free survival as assessed by the IRC, disease control rate as assessed by the IRC and overall survival.

CONTESSA TRIO is a multi-cohort, multicenter, Phase 2 study of tesetaxel, an investigational, orally administered taxane, in patients with locally advanced or metastatic breast cancer (LA/MBC).

In Cohort 1, approximately 90 patients (with potential expansion to up to 150 patients) with locally advanced or metastatic triple-negative breast cancer who have not received prior chemotherapy for advanced disease will be randomised 1: 1: 1 to receive tesetaxel dosed orally at 27 mg/m2 on the first day of each 21-day cycle plus either: (1) nivolumab at 360 mg by intravenous infusion on the first day of each 21-day cycle; (2) pembrolizumab at 200 mg by intravenous infusion on the first day of each 21-day cycle; or (3) atezolizumab at 1,200 mg by intravenous infusion on the first day of each 21-day cycle.

Nivolumab and pembrolizumab (PD-1 inhibitors) and atezolizumab (a PD-L1 inhibitor) are immuno-oncology agents approved for the treatment of multiple types of cancer.

One of these agents, atezolizumab, in combination with the intravenously delivered taxane, nab-paclitaxel, was recently approved by the US Food and Drug Administration as a first-line treatment for patients with metastatic TNBC.

The dual primary endpoints for Cohort 1 are objective response rate and progression-free survival. Secondary endpoints include duration of response and overall survival.

Efficacy results for each of the three PD-(L) inhibitor combinations will be assessed for correlation with the results of each of the three approved PD-L1 diagnostic assays.

In Cohort 2, approximately 40 elderly patients (with potential expansion to up to 60 patients) with human epidermal growth factor receptor 2 negative MBC will receive tesetaxel monotherapy dosed orally at 27 mg/m2 on the first day of each 21-day cycle.

The primary endpoint for Cohort 2 is ORR. Secondary endpoints include PFS, DoR and OS. Patients with central nervous system metastases are eligible for both cohorts.

Odonate's initial focus is on the development of tesetaxel, an investigational, orally administered chemotherapy agent that belongs to a class of drugs known as taxanes, which are widely used in the treatment of cancer.

Odonate's goal for tesetaxel is to develop an effective chemotherapy choice for patients that provides quality-of-life advantages over current alternatives.
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