S. Loi (Melbourne, VI, Australia)
Peter MacCallum Cancer CentreAuthor Of 2 Presentations
Future of PD-1 blockade for ER+ and HER2+ mBC (ID 18)
Stories in breast cancer immunology and genomics (ID 383)
Presenter Of 2 Presentations
Future of PD-1 blockade for ER+ and HER2+ mBC (ID 18)
Stories in breast cancer immunology and genomics (ID 383)
Moderator Of 1 Session
Author Of 1 Presentation
- S. Hurvitz (Santa Monica, CA, United States of America)
- N. Harbeck (Munich, Germany)
- L. Vahdat (New York, NY, United States of America)
- A. Wolff (Baltimore, MD, United States of America)
- S. Tolaney (Boston, MA, United States of America)
- S. Loi (Melbourne, VI, Australia)
- N. Masuda (Osaka, Japan)
- J. O'Shaughnessy (Dallas, TX, United States of America)
- D. Xie (Bothell, WA, United States of America)
- L. Walker (Seattle, WA, United States of America)
- E. Rustia (Bothell, WA, United States of America)
- V. Borges (Lone Tree, CO, United States of America)
126TiP - HER2CLIMB-02: Tucatinib or placebo with T-DM1 for unresectable locally-advanced or metastatic HER2+ breast cancer
Abstract
Background
Tucatinib (TUC), an oral tyrosine kinase inhibitor (TKI) highly selective for HER2 with minimal inhibition of EGFR, is approved in the US, Canada, Switzerland, Australia, and Singapore for combined treatment with trastuzumab (Tras) and capecitabine for patients with HER2+ metastatic breast cancer (MBC), including patients with brain metastases (BM) who received 1 or more prior anti-HER2-based regimens in the metastatic setting. Ado-Tras emtansine (T-DM1), approved for treatment of HER2+ MBC after Tras and a taxane, has improved progression-free survival (PFS) and overall survival (OS). Further improvements are needed, including in patients with active BM. A phase Ib trial evaluated TUC+T-DM1 in 50 patients with HER2+ MBC who received prior treatment with Tras and a taxane; 60% of patients had BM at baseline (Borges 2018). Common adverse events, mostly Grade 1/2, were nausea (72%), diarrhea (60%), and fatigue (56%). Median PFS was 8.2 months and objective response rate (ORR) in patients with measurable disease (n=34) was 47%. Brain specific response rate (RECIST v1.1) in patients with measurable BM (n=14) was 36%. This encouraging clinical activity, including in patients with BM, provides rationale to evaluate TUC+T-DM1.
Trial design
HER2CLIMB-02 is a randomized, double-blind, placebo-controlled, phase III study enrolling patients with centrally confirmed HER2+ unresectable locally-advanced or MBC previously treated with Tras and taxane. Patients must have ECOG ≤1. Approximately 460 patients will be randomized 1:1 for 21-day cycles of TUC (300 mg PO BID) or placebo with T-DM1 (3.6 mg/kg IV). Prior treatment with investigational anti-HER2 agent, anti-EGFR agent, or HER2 TKI is not permitted. Prior pertuzumab treatment is permitted. Baseline brain MRIs are required; patients with stable, progressing, or untreated BM may be eligible. Treatment response assessments per RECISTv1.1 occur every 6 weeks for the first 24 weeks, and then every 9 weeks. Primary endpoint is PFS per investigator assessment, with OS and ORR as key secondary endpoints. Enrollment is ongoing in the US, Canada, EU, Japan, South Korea, Australia, and Israel, and is planned for Singapore.
Clinical trial identification
NCT03975647.
Editorial acknowledgement
Editorial assistance was provided by Craig Bolte of MMS Holdings.
Legal entity responsible for the study
Seagen Inc.
Funding
Seagen Inc.
Disclosure
S.A. Hurvitz: Research grant/Funding (institution): Ambrx, Amgen; Research grant/Funding (institution): AstraZeneca, Arvinas; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Genentech/Roche, Bayer; Research grant/Funding (institution): Gilead, Immunomedics; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution), Travel/Accommodation/Expenses: Eli Lilly; Research grant/Funding (institution): Macrogenetics, Novartis; Research grant/Funding (institution): Pfizer, Obi Pharma; Research grant/Funding (institution): Pieris, Puma; Research grant/Funding (institution): Radius, Sanofi; Research grant/Funding (institution): Seagen Inc.; Research grant/Funding (institution): Dignitana, Zymeworks; Research grant/Funding (institution): Phoenix Molecular Designs, Ltd.; Shareholder/Stockholder/Stock options: Nk Max. N. Harbeck: Honoraria (self): AstraZeneca; Honoraria (self): Daiichi Sankyo; Honoraria (self): Eli Lilly; Honoraria (self): MSD Pharmaceuticals; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): Sandoz/Hexal; Honoraria (self): Seagen Inc. L. Vahdat: Advisory/Consultancy, Research grant/Funding (institution): Arvinas; Advisory/Consultancy: Roche; Advisory/Consultancy: Berg Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai Co., Ltd.; Advisory/Consultancy, Research grant/Funding (institution): Polyphor Pharma; Advisory/Consultancy, Travel/Accommodation/Expenses: Seagen Inc.; Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Oncotherapy Biosciences. S.M. Tolaney: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Daiichi Sankyo, OncoPep; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly, Eisai; Advisory/Consultancy: G1 Therapeutics, Outcomes4Me; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): Immunomedics; Advisory/Consultancy: Kyowa Kirin, Silverback Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): NanoString; Advisory/Consultancy, Research grant/Funding (institution): Nektar, Seagen; Advisory/Consultancy, Research grant/Funding (institution): Novartis, Pfizer; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Cyclacel, Odonate; Advisory/Consultancy: Puma Therapeutics, Sanofi; Advisory/Consultancy: Celldex, Paxman, AbbVie; Advisory/Consultancy: Samsung Bioepsis Inc. S. Loi: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Aduro Biotech; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): Seagen Inc; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Puma Biotech. N. Masuda: Honoraria (self), Research grant/Funding (institution): Chugai Pharma; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Honoraria (self), Research grant/Funding (institution): Eisai; Honoraria (self): Takeda; Research grant/Funding (institution): Kyowa-Kirin; Research grant/Funding (institution): MSD Pharma; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Nippon-Kayaku; Research grant/Funding (institution): Daiichi Sankyo. J. O'Shaughnessy: Advisory/Consultancy: AbbVie, Agendia; Advisory/Consultancy: Amgen Biotech; Advisory/Consultancy: Aptitude Health; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Celgene, Eisai; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy: Genentech; Advisory/Consultancy: Immunomedics; Advisory/Consultancy: Ipsen Biopharma; Advisory/Consultancy: Jounce Therapeutics; Advisory/Consultancy: Eli Lilly, Merck; Advisory/Consultancy: Myriad, Novartis; Advisory/Consultancy: Ondonate Therapeutics; Advisory/Consultancy: Pfizer, Puma Biotech; Advisory/Consultancy: prIME Oncology; Advisory/Consultancy: Roche, Seagen Inc; Advisory/Consultancy: Syndax Pharmaceuticals. D. Xie: Full/Part-time employment: Seagen Inc. L.N. Walker: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Seagen Inc. E. Rustia: Shareholder/Stockholder/Stock options, Full/Part-time employment: Seagen Inc. V. Borges: Advisory/Consultancy, Research grant/Funding (institution): Seagen Inc; Research grant/Funding (institution): Abbot/AbbVie; Research grant/Funding (institution): Millenium. All other authors have declared no conflicts of interest.