Ciara C. O'Sullivan (Rochester, United States of America)
Mayo ClinicAuthor Of 1 Presentation
207TiP - Phase 3 study of tucatinib or placebo in combination with trastuzumab and pertuzumab as maintenance therapy for HER2+ metastatic breast cancer (HER2CLIMB-05, trial in progress) (ID 215)
- Veronique Dieras (Rennes, France)
- Miguel Martin Jimenez (Madrid, Spain)
- Ciara C. O'Sullivan (Rochester, United States of America)
- Joohyuk Sohn (Seoul, Korea, Republic of)
- KONSTANTINOS TRYFONIDIS (North Wales, United States of America)
- Libero Santarpia (Bothell, United States of America)
- Shan Yang (Bothell, United States of America)
- Erika P. Hamilton (Nashville, United States of America)
Abstract
Background
The current first-line (1L) standard of care (SOC) for human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) is trastuzumab (T) plus pertuzumab (P) and a taxane. Despite advances in 1L SOC, most patients (pts) progress during maintenance therapy with T+P. Tucatinib is a tyrosine kinase inhibitor (TKI) approved in combination with T and capecitabine for adults with HER2+ MBC, with and without brain metastases (BM). In HER2CLIMB, the addition of tucatinib significantly prolonged progression-free survival (PFS) and overall survival (OS) in pts with HER2+ MBC and was well tolerated. Adding tucatinib also reduced the risk of disease progression or death in pts with untreated and/or active BM (Murthy et al. 2020, Curigliano et al. 2021). HER2CLIMB-05 investigates whether adding tucatinib to 1L SOC as maintenance therapy will extend PFS while maintaining quality of life (QOL).
Trial design
HER2CLIMB-05 (NCT05132582) is a phase 3, randomized, double-blind study evaluating tucatinib plus T+P as maintenance therapy for HER2+ MBC. Approximately 650 pts will be enrolled. Eligible pts will have advanced HER2+ disease, no progression on 4–8 cycles of prior 1L SOC, ECOG Performance Status of 0 or 1, and no or asymptomatic BM. Exclusion criteria include prior treatment with anti-HER2 and/or anti-epidermal growth factor receptor TKI (prior SOC for early BC is permitted) or inability to undergo contrast magnetic resonance imaging of the brain. Pts will be randomized 1:1 to receive either tucatinib or placebo twice daily, with T+P once every 21 days. Pts with HR+ disease may receive endocrine therapy. The primary endpoint is investigator-assessed PFS. Secondary endpoints include OS (key endpoint), time to deterioration of health-related QOL, central nervous system PFS, safety, and pharmacokinetic (PK) parameters. PFS and OS will be compared using a 2-sided stratified log-rank test between treatment groups. Time-to-event endpoints will be summarized using the Kaplan–Meier method. PK and safety data will be summarized using descriptive statistics. Enrollment is ongoing in the US, with additional sites planned.
Clinical trial identification
NCT05132582.
Legal entity responsible for the study
Seagen Inc.
Funding
Seagen Inc.
Disclosure
V.C. Dieras: Financial Interests, Personal, Other, Travel Expenses: Roche, Novartis, Pfizer, Lilly, AstraZeneca, Daiichi Sankyo, Seagen, Gilead; Financial Interests, Personal, Advisory Board, Consultant/Advisory Board: Roche/Genentech, Novartis, Lilly, Pfizer, AstraZeneca, AbbVie, MSD, Daiichi Sankyo, Seagen, Gilead, Eisai, Pierre Fabre Oncologie; Financial Interests, Personal, Other, Symposia: Roche, Novartis, Pfizer, Lilly, AstraZeneca, Daiichi Sankyo, Seagen, Gilead. M. Martin Jimenez: Financial Interests, Personal, Advisory Board: Roche, Lilly, Novartis, Pierre Fabre, Pfizer, Daiichi Sankyo, Seagen; Financial Interests, Personal, Other, Honoraria: Roche, Lilly, Novartis, Pierre Fabre, Pfizer, Daiichi Sankyo, Seagen; Financial Interests, Personal, Funding, Research Funding/Grants: Puma, Roche, Novartis. C.C.M. O'Sullivan: Financial Interests, Personal, Full or part-time Employment: Mayo Clinic Rochester; Financial Interests, Personal, Funding, Research Funding/Grants: Lilly, Seattle Genetics, Bavarian Nordic, Minnemarita Therapeutics, Biovica. J. Sohn: Financial Interests, Personal, Funding: Seagen Inc. K. Tryfonidis: Financial Interests, Personal, Full or part-time Employment: Merck. L. Santarpia, S. Yang: Financial Interests, Personal, Full or part-time Employment: Seagen Inc. E.P. Hamilton: Financial Interests, Institutional, Other, Consulting/Advisory Role: Genentech/Roche, Boehringer Ingelheim, Novartis, Dantari, Lilly, Merck, Puma Biotechnology, Silverback Therapeutics, CytomX, Pfizer, Mersana, Black Diamond, H3 Biomedicine, Daiichi Sankyo, AstraZeneca, Arvinas, Deciphera Pharmaceuticals, Eisai, Seagen, Arcus, iTeos, Janssen, Loxo, Relay Therapeutics; Financial Interests, Institutional, Research Grant: Oncomed, Genentech/Roche, Zymeworks, Rgenix, Arqule, Clovis, Silverback Therapeutics, Millenium, Acerta Pharma, Sermonix Pharmaceuticals, Black Diamond, Karyopharm, Curis, Syndax, Novartis, Boehringer Ingelheim, Immunomedics, FujiFilm, Taiho, Deciphera, Fochon, Molecular Templates, Onconova Therapeutics, Dana Farber Cancer Hospital, Hutchinson MediPharma, MedImmune, Seagen, Compugen, TapImmune, Lilly, Pfizer, H3 Biomedicine, Merus, Regeneron, Arvinas, StemCentRx, Verastem, eFFECTOR Therapeutics, CytomX, InventisBio, Lycera, Mersana, Radius Health, AbbVie, Nucana, Orinove, Leap Therapeutics, Zenith Epigenetics, Harpoon, AstraZeneca, Tesaro, Macrogenics, EMD Serono, Daiichi Sankyo, Syros, Sutro, G1 Therapeutics, Merck, PharmaMar, Olema, Immunogen, Plexxicon, Amgen, Akesobio Australia, Shattuck Labs, ADC Therapeutics, Aravive, Atlas MedX, Ellipses, Incyte, Jacobio, Mabspace Biosciences, Myraid Genetic Labs, ORIC Pharmaceuticals, Pieris Pharmaceuticals; Financial Interests, Institutional: Pionyr Immunotherapeutics.