V. Kang (Bothell, WA, United States of America)
Seagen Inv.Author Of 1 Presentation
125TiP - SGNTUC-019: Phase 2 basket study of tucatinib and trastuzumab in previously treated solid tumors with HER2 alterations: HER2-mutated breast cancer cohort (Trial in Progress)
Abstract
Background
Tucatinib (TUC), a highly selective HER2-directed TKI recently approved for HER2 overexpressed/amplified (HER2+) metastatic breast cancer (BC), on the basis of a statistically significant and clinically meaningful PFS, OS, and ORR benefit for the addition of TUC to trastuzumab (Tras) and capecitabine. TUC is being developed as a novel therapy for patients (pts) with metastatic BC, CRC, and gastric cancer. In xenograft models of HER2+ and HER2-mutated (HER2-mut) tumors, dual targeting of HER2 with TUC and Tras showed superior activity to either agent alone. The SGNTUC-019 basket study is evaluating TUC in combination with Tras in pts with HER2+ or HER2-mut solid tumors, including a cohort of pts with locally advanced unresectable or metastatic (LAUM) HER2-mut BC.
Trial design
SGNTUC-019 is a multi-cohort, open-label, international phase II study evaluating pts with previously treated solid tumors displaying HER2 overexpression/amplification or activating mutations. Eligible pts must have HER2+ or HER2-mut LAUM solid tumors, with progression on or after the last systemic therapy for advanced disease, be ≥18 years old, with ECOG PS ≤1, adequate hepatic, hematological, renal, and cardiac function, and no prior HER2-directed therapy. For eligibility, HER2-mut can be demonstrated in a prior or on-study NGS assay of ctDNA or prior tissue NGS assay. The BC cohort will enroll 30 response-evaluable pts with HER2-mut disease. Pts with HER2+ BC will not be enrolled. The primary objective is antitumor activity in each cohort, with confirmed ORR as primary endpoint, and disease control rate, duration of response, PFS, and OS as secondary endpoints. Pts will receive TUC 300 mg PO BID and Tras 8 mg/kg IV on Cycle (C) 1 Day (D) 1 and 6 mg/kg q21 days from C2 D1. Hormone receptor positive BC pts will also receive fulvestrant 500 mg IM every 4 weeks and C1 D15. Disease assessments per RECIST 1.1 are q6 weeks for 24 weeks, then q12 weeks. Pts with brain metastases may be eligible; pts in the BC and lung cancer cohorts will undergo baseline brain MRI. Quality of life will be evaluated q2 cycle using EQ-5D-5L. Sites are open in the US; EU and Asia will be opened. Enrollment began in Dec 2020.
Clinical trial identification
NCT04579380.
Editorial acknowledgement
William Sutherland, freelance, assisted in the preparation of this abstract.
Legal entity responsible for the study
Seagen Inc.
Funding
Seagen Inc.
Disclosure
A. Okines: Research grant/Funding (self): Roche; Advisory/Consultancy: Roche; Travel/Accommodation/Expenses: Leo Pharmaceuticals; Honoraria (self): Seagen; Advisory/Consultancy: Seagen; Research grant/Funding (self): Pfizer; Travel/Accommodation/Expenses: AstraZeneca/Daiichi Sankyo; Honoraria (self): AstraZeneca/Daiichi Sankyo. V. Kang: Full/Part-time employment: Seagen; Shareholder/Stockholder/Stock options: Myovant Sciences. L.N. Walker: Full/Part-time employment: Seagen; Travel/Accommodation/Expenses: Seagen; Licensing/Royalties: Seagen; Shareholder/Stockholder/Stock options: Seagen. P.R. Pohlmann: Advisory/Consultancy, Leadership role, Shareholder/Stockholder/Stock options: Immunonet Biosciences; Advisory/Consultancy: Perthera; Advisory/Consultancy: Sirtex; Advisory/Consultancy: Xcenda; Advisory/Consultancy: CARIS; Advisory/Consultancy: OncoPlex Diagnostics; Advisory/Consultancy: Heron; Advisory/Consultancy: Puma; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): Pieris; Advisory/Consultancy, Research grant/Funding (institution): Seagen; Research grant/Funding (institution): Bolt; Research grant/Funding (institution): Byondis.