W. Feng (Bothell, AL, United States of America)
SeagenAuthor Of 1 Presentation
128TiP - HER2CLIMB-04: Phase 2 trial of tucatinib + trastuzumab deruxtecan in patients with HER2+ unresectable locally-advanced or metastatic breast cancer with and without brain metastases (Trial in Progress)
Abstract
Background
Tucatinib (TUC) is an oral, reversible, small molecule tyrosine kinase inhibitor highly selective for human epidermal growth factor receptor 2 (HER2). In the HER2CLIMB trial (NCT02614794), the combination of TUC + trastuzumab (T) + capecitabine (C) demonstrated statistically significant and clinically meaningful improvement in progression free survival (PFS), overall survival (OS), and PFS in patients (pts) with brain metastases (BM) compared to T + C alone, supporting regulatory approvals internationally for pts with HER2+ metastatic breast cancer (MBC). Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate with a topoisomerase I inhibitor payload approved in the US for treatment of HER2+ MBC in pts who have received 2 or more prior anti-HER2 regimens in the metastatic setting. Approval was based on data from the Destiny-Breast01 trial (NCT03248492) where treatment with T-DXd resulted in a confirmed objective response rate (cORR) of 61.4% (95% CI: 54.0, 68.5) in pts with HER2+ MBC who had prior ado-trastuzumab emtansine treatment. Despite these advances, HER2+ MBC remains incurable, and pts will eventually progress on currently available therapies. Combining TUC and T-DXd may result in further improvement on the efficacy seen with either agent.
Trial design
HER2CLIMB-04 (NCT04539938) is a single arm, open-label phase II trial evaluating safety and antitumor activity of TUC + T-DXd in pts with HER2+ unresectable locally-advanced or MBC who have received 2 or more prior HER2-based regimens in the metastatic setting. Pts with BM, including active BM, may be enrolled. Ten pts will be enrolled in the safety lead-in portion of the study and followed for at least 1 cycle. If safety of the combination is acceptable, the trial will continue until approximately 60 response-evaluable pts have been enrolled, approximately evenly distributed between pts with and without BM. The primary endpoint is cORR by investigator (INV) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints are PFS, duration of response, and disease control rate by INV per RECIST v1.1, OS, and safety. Enrollment began in late 2020.
Clinical trial identification
NCT04539938.
Editorial acknowledgement
Editorial/writing assistance was provided by Wendi Schultz and Aulma Parker of Seagen Inc.
Legal entity responsible for the study
Seagen Inc.
Funding
Seagen Inc.
Disclosure
E. Hamilton: Advisory/Consultancy, Paid to Institution Only: Pfizer, Genentech/Roche, Lilly, Puma Biotechnology, Daiichi Sankyo, Mersana Therapeutics, Boehringer Ingelheim, AstraZeneca, Novartis, Silverback Therapeutics, Black Diamond, and NanoString; Research grant/Funding (institution), Paid to Institution Only: Seagen Inc., Puma, AstraZeneca, Hutchinson MediPharma, OncoMed, MedImmune, StemCentrx, Genentech/Roche, Curis, Verastem, Zymeworks, Syndax, Lycera, Rgenix, Novartis, Mersana, Millenium, TapImmune, Lilly, BerGenBio, Medivation, Pfizer, Tesaro, Boehringer Ingelheim. J. Ramos: Shareholder/Stockholder/Stock options: Seagen Inc.; Full/Part-time employment: Seagen Inc. W. Feng: Shareholder/Stockholder/Stock options: Seagen Inc.; Full/Part-time employment: Seagen Inc. I. Krop: Honoraria (self): Celltrion; Advisory/Consultancy: Daiichi Sankyo, Genentech/Roche, Ionis Pharma, Macrogenics, Merck, Novartis, Seagen Inc., Celltrion, BMS; Advisory/Consultancy, DSMB membership: Merck, Novartis; Research grant/Funding (institution): Daiichi Sankyo, Genentech, Pfizer, Seagen, Taiho Oncology; Spouse/Financial dependant, Stock/Stockholder, Leadership, and/or Employment: AMAG Pharma, Freeline.