Abstract 331TiP
Background
Tucatinib (TUC) is an oral, reversible, small-molecule tyrosine kinase inhibitor highly selective for human epidermal growth factor receptor 2 (HER2). TUC + trastuzumab (T) + capecitabine (C) is approved for patients (pts) with locally advanced or metastatic breast cancer (MBC) after ≥2 prior anti-HER2 treatment regimens based on statistically significant, clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) in pts with and without brain metastases (BM) in the randomized HER2CLIMB trial (NCT02614794). Trastuzumab deruxtecan (T-DXd) is an antibody–drug conjugate composed of T and a topoisomerase I inhibitor payload. T-DXd was approved for pts with unresectable or MBC after ≥2 prior anti-HER2 treatment regimens, based on the confirmed objective response rate (cORR) in the single-arm DESTINY-Breast01 trial (NCT03248492). Despite these advances, HER2+ MBC remains incurable and pts will ultimately progress on currently available therapies. Combining TUC and T-DXd may enhance the efficacy as compared with that of the individual agents.
Trial design
HER2CLIMB-04 (NCT04539938) is a single-arm, open-label phase 2 trial evaluating the efficacy and safety of TUC + T-DXd in pts with HER2+ unresectable, locally advanced or MBC with ≥2 prior HER2-based regimens in the metastatic setting in the US. Pts with BM, including active BM, may be included. A safety lead-in portion of the trial will enroll 10 patients who will be followed for ≥1 cycle. If safety of TUC + T-DXd is acceptable, the trial will enroll ∼60 response-evaluable pts, evenly distributed between pts with and without BM. The primary endpoint is cORR by investigator (INV) assessment per RECIST v1.1. Secondary endpoints are PFS, duration of response (DOR), disease control rate (DCR), OS, and safety. Exploratory endpoints will include cORR, PFS, DCR, and DOR by independent central review per RECIST v1.1, pharmacokinetic and biomarker analyses, and changes in patient-reported outcomes (European Quality of Life 5-Dimension 5-Level). Enrollment began in late 2020.
Clinical trial identification
NCT04539938.
Editorial acknowledgement
Medical writing support was provided by Elliot Piper-Brown, PhD, and editorial support by Travis Taylor, BA, all of Scion, London, supported by Seagen Inc.
Legal entity responsible for the study
Seagen Inc.
Funding
Seagen Inc.
Disclosure
L.A. Carey: Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: G1 Therapeutics; Financial Interests, Institutional, Research Grant: Genentech/Roche; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Innocrin Pharma; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Immunomedics; Financial Interests, Institutional, Royalties, Institutional financial interests with commercial entity: Falcon Therapeutics; Financial Interests, Institutional, Research Grant, Research funding/grants: AbbVie; Financial Interests, Institutional, Research Grant, Research funding/grants: Immunomedics; Financial Interests, Institutional, Research Grant, Research funding/grants: Innocrin Pharma; Financial Interests, Institutional, Research Grant, Research funding/grants: NanoString; Financial Interests, Institutional, Research Grant, Research funding/grants: Novartis; Financial Interests, Institutional, Research Grant, Research funding/grants: Seagen; Financial Interests, Institutional, Research Grant, Research funding/grants: Syndax; Non-Financial Interests, Institutional, Invited Speaker, Uncompensated relationship: Aptitude Health; Non-Financial Interests, Institutional, Other, Uncompensated relationship: AstraZeneca/Daiichi Sankyo; Non-Financial Interests, Institutional, Other, Uncompensated relationship: Exact Sciences; Non-Financial Interests, Institutional, Other, Uncompensated relationship: G1 Therapeutics; Non-Financial Interests, Institutional, Other, Uncompensated relationship: Genentech/Roche; Non-Financial Interests, Institutional, Other, Uncompensated relationship: GlaxoSmithKline; Non-Financial Interests, Institutional, Other, Uncompensated relationship: Novartis; Non-Financial Interests, Institutional, Other, Uncompensated relationship: Sanofi. I. Krop: Financial Interests, Personal, Other, Consultancy: Daiichi Sankyo; Financial Interests, Personal, Other, Consultancy: Genentech/Roche; Financial Interests, Personal, Other, Consultancy: Ionis Pharma; Financial Interests, Personal, Other, Consultancy: Macrogenics; Financial Interests, Personal, Other, Consultancy: Merck; Financial Interests, Personal, Other, Consultancy: Novartis; Financial Interests, Personal, Other, Consultancy: Seagen; Financial Interests, Personal, Other, Honoraria: Celltrion; Financial Interests, Institutional, Other, Research grant/Funding: Genentech; Financial Interests, Institutional, Other, Research grant/Funding: Pfizer; Financial Interests, Personal, Other, Consultancy: Taiho Pharma; Financial Interests, Personal, Other, Consultancy: Bristol Myers Squibb; Financial Interests, Personal, Other, Consultancy: Context Therapeutics; Financial Interests, Personal and Institutional, Full or part-time Employment: AMAG Pharma; Financial Interests, Personal and Institutional, Full or part-time Employment: Freeline Therapeutics; Financial Interests, Personal and Institutional, Full or part-time Employment: AMAG Pharma; Financial Interests, Personal and Institutional, Full or part-time Employment: Freeline Therapeutics; Financial Interests, Personal and Institutional, Full or part-time Employment: Vertex; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Genentech/Roche. J. Ramos: Financial Interests, Institutional, Stocks/Shares, Employee and equity ownership: Seagen Inc. W. Feng: Financial Interests, Institutional, Ownership Interest, Institutional financial interests with commercial entity: Employee and equity ownership. E. Hamilton: Financial Interests, Personal, Other, Consultancy: Arvinas; Financial Interests, Personal, Other, Consultancy: AstraZeneca; Financial Interests, Personal, Other, Consultancy: Black Diamond Therapeutics; Financial Interests, Personal, Other, Consultancy: Boehringer Ingelheim; Financial Interests, Personal, Other, Consultancy: CytomX Therapeutics; Financial Interests, Personal, Other, Consultancy: Daiichi Sankyo; Financial Interests, Personal, Other, Consultancy: Dantari; Financial Interests, Personal, Other, Consultancy: Deciphera; Financial Interests, Personal, Other, Consultancy: Eisai; Financial Interests, Personal, Other, Consultancy: Genentech/Roche; Financial Interests, Personal, Other, Consultancy: H3 Biomed; Financial Interests, Personal, Other, Consultancy: Lilly; Financial Interests, Personal, Other, Consultancy: Merck; Financial Interests, Personal, Other, Consultancy: Mersana; Financial Interests, Personal, Other, Consultancy: Novartis; Financial Interests, Personal, Other, Consultancy: Pfizer; Financial Interests, Personal, Other, Consultancy: Puma Biotech; Financial Interests, Personal, Other, Consultancy: Seagen; Financial Interests, Personal, Other, Consultancy: Silverback Therapeutics; Financial Interests, Institutional, Other, Research Funding/Grants: AbbVie; Financial Interests, Institutional, Other, Research Funding/Grants: Acerta; Financial Interests, Institutional, Other, Research Funding/Grants: Amgen; Financial Interests, Institutional, Other, Research Funding/Grants: ArQule; Financial Interests, Institutional, Other, Research Funding/Grants: Arvinas; Financial Interests, Institutional, Other, Research Funding/Grants: Black Diamond; Financial Interests, Institutional, Other, Research Funding/Grants: Boehringer Ingelheim; Financial Interests, Institutional, Other, Research Funding/Grants: Clovis; Financial Interests, Institutional, Other, Research Funding/Grants: Compugen; Financial Interests, Institutional, Other, Research Funding/Grants: Curis; Financial Interests, Institutional, Other, Research Funding/Grants: Daiichi Sankyo; Financial Interests, Institutional, Other, Research Funding/Grants: Dana Farber; Financial Interests, Institutional, Other, Research Funding/Grants: Deciphera; Financial Interests, Institutional, Other, Research Funding/Grants: Effector; Financial Interests, Institutional, Other, Research Funding/Grants: EMD Serono; Financial Interests, Institutional, Other, Research Funding/Grants: Fochon; Financial Interests, Institutional, Other, Research Funding/Grants: Fosun; Financial Interests, Institutional, Other, Research Funding/Grants: Fujifilm; Financial Interests, Institutional, Other, Research Funding/Grants: G1; Financial Interests, Institutional, Other, Research Funding/Grants: Genentech/Roche; Financial Interests, Institutional, Other, Research Funding/Grants: H3; Financial Interests, Institutional, Other, Research Funding/Grants: Harpoon; Financial Interests, Institutional, Other, Research Funding/Grants: Hutchison Medicpharma; Financial Interests, Institutional, Other, Research Funding/Grants: Immunogen; Financial Interests, Institutional, Other, Research Funding/Grants: Immunomedics; Financial Interests, Institutional, Other, Research Funding/Grants: Infinity; Financial Interests, Institutional, Other, Research Funding/Grants: InventisBio; Financial Interests, Institutional, Other, Research Funding/Grants: Karyopharm; Financial Interests, Institutional, Other, Research Funding/Grants: Leap; Financial Interests, Institutional, Other, Research Funding/Grants: Lilly; Financial Interests, Institutional, Other, Research Funding/Grants: Lycera; Financial Interests, Institutional, Other, Research Funding/Grants: Macrogenics; Financial Interests, Institutional, Other, Research Funding/Grants: MedImmune; Financial Interests, Institutional, Other, Research Funding/Grants: Merck; Financial Interests, Institutional, Other, Research Funding/Grants: Mersana; Financial Interests, Institutional, Other, Research Funding/Grants: Merus; Financial Interests, Institutional, Other, Research Funding/Grants: Millennium; Financial Interests, Institutional, Other, Research Funding/Grants: Molecular Templates; Financial Interests, Institutional, Other, Research Funding/Grants: Novartis; Financial Interests, Institutional, Other, Research Funding/Grants: Nucana; Financial Interests, Institutional, Other, Research Funding/Grants: Olema; Financial Interests, Institutional, Other, Research Funding/Grants: OncoMed; Financial Interests, Institutional, Other, Research Funding/Grants: Onconova; Financial Interests, Institutional, Other, Research Funding/Grants: Pfizer; Financial Interests, Institutional, Other, Research Funding/Grants: PharmaMar; Financial Interests, Institutional, Other, Research Funding/Grants: Plexxikon; Financial Interests, Institutional, Other, Research Funding/Grants: Polyphor; Financial Interests, Institutional, Other, Research Funding/Grants: Puma; Financial Interests, Institutional, Other, Research Funding/Grants: Radius.