FDA Feedback Leads to Discontinuation of Tesetaxel Development in Solid Tumors

Clinical development of the oral chemotherapy agent, tesetaxel is being discontinued as the treatment of metastatic breast cancer (mBC), colorectal cancer, and other solid tumors after the FDA provided feedback on a pre-New Drug Application, according to a press release issued by Odonate Therapeutics.¹

According to the company, the clinical package data for the tesetaxel is unlikely to support FDA approval.

Over 1200 people have been treated with tesetaxel in 26 clinical studies. In 19 studies, it was administered as a monotherapy, and it was administered in a combination regimen in the remaining 7 studies. Tesetaxel has also been investigated in, gastric cancer, non-small cell lung cancer, and other solid tumors as a first-line therapy, second-line therapy, and salvage therapy.2

One major trial involving tesetaxel was the CONTESSA trial (NCT03326674), which was a multicenter, randomized, phase 3 study of tesetaxel plus a reduced dose of capecitabine versus the approved dose of capecitabine alone as treatment of mBC. The study enrolled 685 patients, of which 674 received treatment.

Participants assigned to arm A received tesetaxel orally once every 21 days on day 1 of each 21-day cycle and 2 doses of 825 mg/m2 capecitabine daily on days 1 through 15 of each 21-day cycle. The patients in arm B received 1,250 mg/m2 of capecitabine twice daily from day 1 through 15 of each 21-day cycle.

The primary outcome of the study was progression-free survival (PFS). Secondary outcomes included overall survival (OS), overall response rate (ORR), and duration of complete response (DCR). In order to be eligible, patients must be at least 18 years old, have confirmed HER2-negative BC and at least one prior therapy. Patients with two or more prior chemotherapy regimens for advanced disease were excluded.²

Patients on the combination demonstrated a PFS of 9.78 months compared with the 6.9 months of patients on capecitabine alone (HR, 0.716; 95% CI, 0.573-0.895; P = .003).

The ORR was 57% in the combination group versus the 41% for the capecitabine alone (P = .0002).

Tesetaxel was also studied in HR-positive, HER2- negative mBC. The trial, known as CONTESSA 2 (NCT03858972), enrolled 150 patients who were previously treated with a taxane. Participants were administered 27mg/m2 of tesetaxel orally on day 1 of a 21-day cycle plus a reduced dose of capecitabine, 1650 mg/m2/day for 14 days of a 21-day cycle. The primary endpoint of the study was ORR. Secondary endpoints included duration or response (DOR) and PFS.

Tesetaxel was also under investigation in the CONTESSA TRIO (NCT03952325) study. Cohort 1 included approximately 200 patients with triple-negative MBC with no prior chemotherapy for advanced disease. In order to enroll, patients needed to prove positive PD-L1 expression. Patients were randomized 1:1:1 to receive either 27 mg/m2 of tesetaxel plus 360 mg of nivolumab once every 3 weeks, 27 mg/m2 of tesetaxel plus 200 mg of pembrolizumab once every 3 weeks, or 27 mg/m2 of tesetaxel plus 1200 mg of atezolizumab once every 3 weeks. Primary endpoints for this cohort included ORR and PFS in patients with PD-L1-positive status. Secondary endpoints included ORR and PFS in all patients.

Cohort 2 included 69 elderly patients with HER2-negative mBC with no prior chemotherapy treatment for advanced disease. This cohort received tesetaxel as a monotherapy dosed orally at 27 mg/m2 on day 1 of a 21-day cycle. Cohort 3 was the same except that the 60 patients were non-elderly.²

According to Odonate, all patients currently receiving tesetaxel as part of a clinical trial will transition to an appropriate alternative therapy.¹

_REFERENCE:

_{1. Odonate Therapeutics announces discontinuation of development of tesetaxel. News Release. March 22, 2021. Accessed March 23, 2021. https://bit.ly/3u1rMPh}

_{2. ESETAXEL. Odonate Acces sed March 23, 2021. https://bit.ly/3tG6dn4}