Results from CONTESSA 2: A multinational, multicenter, phase 2 study of tesetaxel (T) plus a reduced dose of capecitabine (C) in patients (pts) with hormone receptor + (HR+), HER2- metastatic breast cancer (MBC) not previously treated with a taxane.

1061 Research Funding: Odonate Therapeutics, Inc. Background: T is a novel, oral taxane with unique properties, including: oral administration with a low pill burden, a long (8-day) half-life in humans, once-every-3-weeks dosing, no observed hypersensitivity reactions and significant activity against chemotherapy (CT)-resistant breast cancer cell lines. T had encouraging monotherapy activity in a phase 2 study in 38 pts with HR+, HER2- MBC, with a confirmed objective response rate (ORR) per RECIST 1.1 of 45% (Seidman, 2018 ASCO Annual Meeting, Abstract 1042). In CONTESSA, a randomized phase 3 study in 685 pts with HR+, HER2- MBC previously treated with a taxane, T plus a reduced dose of C improved progression-free survival (PFS) as assessed by the Independent Radiologic Review Committee (IRC) vs. the approved dose of C alone: median of 9.8 months (mo) vs. 6.9 mo, an improvement of 2.9 mo (HR=0.716; p=0.003) (O'Shaughnessy, SABCS 2020, GS4-01). Methods: CONTESSA 2 is a multinational, multicenter, phase 2 study of T (27 mg/m2 on day 1 of a 21-day cycle) plus a reduced dose of C (1,650 mg/m2/day for 14 days of a 21-day cycle) in pts with HR+, HER2- MBC previously treated with 0-1 prior CT regimens for MBC and not previously treated with a taxane. The primary endpoint is ORR as assessed by the IRC. The secondary efficacy endpoints are duration of response (DoR), PFS and disease control rate (DCR) as assessed by the IRC, and overall survival (OS). Results: 150 pts were enrolled and treated. 80% had visceral disease, 46% had de novo MBC, 52% were previously treated with a CDK 4/6 inhibitor and 33% were ≥65 years old. At the prespecified interim analysis approx 4 mo after the last patient enrolled, the confirmed ORR was 51% (95% CI: 42%-60%), and the unconfirmed ORR was 63% (95% CI: 54%-71%). The median DoR was 9.5 mo (95% CI: 5.4-11.5 mo), the median PFS was 12.9 mo (95% CI: 8.1 mo-NR) and the DCR was 71% (95% CI: 62%-79%). OS data are immature. Grade (Gr) ≥3 treatment-emergent adverse events (TEAEs) occurring in ≥5% of pts were: neutropenia (74.0%), leukopenia (10.7%), hypokalemia (7.3%), anemia (6.7%), hand-foot syndrome (6.0%) and diarrhea (5.3%). Gr 2 alopecia occurred in 11.3% of pts, febrile neutropenia occurred in 4.7% of pts and Gr ≥3 neuropathy occurred in 2.0% of pts. Discontinuation of T and C due to any adverse event occurred in 13.3% of pts. Conclusions: An all-oral regimen of T plus a reduced dose of C demonstrated a high level of antitumor activity in pts with HR+, HER2- MBC not previously treated with a taxane. The confirmed ORR was 51%, median DoR was 9.5 mo and median PFS was 12.9 mo. Neutropenia was the most frequent Gr ≥3 TEAE; the rate of febrile neutropenia was 4.7%. Rates of clinically significant alopecia and neuropathy were low. Clinical trial information: NCT03858972 . Clinical trial information: NCT03858972 .

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