Abstract 557TiP
Background
Tucatinib (TUC), a highly selective HER2-directed TKI with minimal EGFR inhibition, is approved in combination with trastuzumab (Tras) and capecitabine for adult patients (pts) with HER2 overexpressed/amplified (HER2+) locally-advanced unresectable or metastatic (LAUM) breast cancer (BC). Dual targeting of HER2 with TUC and Tras showed superior activity to either agent alone in HER2+ and HER2-mutated (HER2-mut) xenograft models. Currently, HER2-directed therapies are approved only in HER2+ BC and gastric cancer. The SGNTUC-019 basket study is evaluating TUC and Tras in pts with HER2+ or HER2-mut LAUM solid tumors.
Trial design
SGNTUC-019 is a multi-cohort, open-label, phase 2 study. Cohorts will enroll pts with HER2+ cervical, uterine, biliary tract, and urothelial cancers, non-squamous NSCLC, other HER2+ solid tumors (except GEC, BC, and CRC), HER2-mut non-squamous NSCLC, BC, and other solid tumors. HER2 alterations are demonstrated by prior tissue IHC/ISH, prior or on-study ctDNA NGS, or prior tissue NGS assays. Eligible pts must have progressed on or after the last systemic therapy for advanced disease (metastatic cervical cancer: prior platinum-based chemotherapy ± bevacizumab required; HR+ HER2-mut BC: a prior CDK4/6 inhibitor required). Pts must be ≥18 years, with ECOG PS ≤1, adequate hepatic, hematological, renal, coagulation, and cardiac function, and no prior HER2-directed therapy (exceptions apply). Pts receive TUC 300 mg PO BID and Tras 8 mg/kg IV on C1 D1 then 6 mg/kg q21 days. HR+ BC pts also receive fulvestrant 500 mg IM q4 weeks. Twelve response-evaluable pts will be enrolled in each cohort. If ≥2 responses are observed, the cohort will be expanded to 30 pts. The other solid tumor and HER2-mut BC cohorts will enroll 30 pts in a single stage. Other disease-specific cohorts may be opened. Approximately 162-270 pts are planned. Primary objective is antitumor activity. Confirmed ORR per investigator is primary endpoint; secondary endpoints are disease control rate, DOR, PFS, and OS. Disease assessments per RECIST 1.1 will occur q6 weeks for 24 weeks, then q12 weeks. EQ-5D-5L QoL is evaluated q2 cycles. Enrollment in US sites began in Dec 2020; EU and Asia sites will be opened.
Clinical trial identification
NCT04579380; April 28, 2021.
Editorial acknowledgement
The authors wish to thank William Sutherland, freelance, for assistance in the preparation of this abstract.
Legal entity responsible for the study
The authors wish to thank William Sutherland, freelance, for assistance in the preparation of this abstract.
Funding
Seagen Inc.
Disclosure
M. Reck: Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: MSD Oncology; Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Roche/Genentech; Financial Interests, Personal, Advisory Role: Abbvie; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Mirati Therapeutics; Financial Interests, Personal, Advisory Role: Samsung Bioepis; Financial Interests, Personal, Speaker’s Bureau: Roche/Genentech; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Speaker’s Bureau: MSD Oncology; Financial Interests, Personal, Speaker’s Bureau: Merck Serono; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Bristol-Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Celgene; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Speaker’s Bureau: Mirati Therapeutics. A. Okines: Financial Interests, Personal, Advisory Role: Roche/Genentech; Financial Interests, Personal, Advisory Role: Seagen; Financial Interests, Personal, Speaker’s Bureau: Seagen; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Leo Pharma; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Daiichi Sankyo Europe GmbH; Financial Interests, Personal, Stocks/Shares: AstraZeneca; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Roche/Genentech. P.R. Pohlmann: Financial Interests, Personal, Advisory Role: Personalized Cancer Therapy; Financial Interests, Personal, Advisory Role: OncoPlex Diagnostics; Financial Interests, Personal, Advisory Role: Immunonet BioSciences; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: HERON; Financial Interests, Personal, Advisory Role: Puma Biotechnology; Financial Interests, Personal, Advisory Role: Sirtex Medical; Financial Interests, Personal, Advisory Role: Caris Life Sciences; Financial Interests, Personal, Advisory Role: Juniper Pharmaceuticals; Financial Interests, Personal, Leadership Role: Immunonet BioSciences; Financial Interests, Personal, Speaker’s Bureau: Genentech/Roche; Financial Interests, Personal, Stocks/Shares: Immunonet BioSciences; Financial Interests, Personal, Other, Honoraria: Dava Oncology; Financial Interests, Personal, Other, Honoraria: OncLive/MJH Life Sciences; Financial Interests, Personal, Other, Honoraria: Frontiers - Publisher; Financial Interests, Institutional, Research Grant: Genentech/Roche; Financial Interests, Institutional, Research Grant: Fabre-Kramer; Financial Interests, Institutional, Research Grant: Advanced Cancer Therapeutics; Financial Interests, Institutional, Research Grant: Caris Centers of Excellence; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Pieris Pharmaceuticals; Financial Interests, Institutional, Research Grant: Cascadian Therapeutics; Financial Interests, Institutional, Research Grant: Bolt Biotherapeutics; Financial Interests, Institutional, Research Grant: Byondis; Financial Interests, Institutional, Research Grant: Seagen. E. Yu: Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Clovis; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Abbvie; Financial Interests, Personal, Advisory Role: Advanced Accelerator Applications; Financial Interests, Personal, Advisory Role: Exelixis; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Dendreon; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Pharmacyclics; Financial Interests, Institutional, Research Grant: Seagen; Financial Interests, Institutional, Research Grant: Advanced Accelerator Applications; Financial Interests, Institutional, Research Grant: Daiichi-Sankyo; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: Blue Earth. T. Bekaii-Saab: Financial Interests, Institutional, Advisory Role: Amgen; Financial Interests, Institutional, Advisory Role: Ipsen; Financial Interests, Institutional, Advisory Role: Lilly; Financial Interests, Institutional, Advisory Role: Bayer; Financial Interests, Institutional, Advisory Role: Roche/Genentech; Financial Interests, Personal, Advisory Role: Abbvie; Financial Interests, Institutional, Advisory Role: Incyte; Financial Interests, Personal, Advisory Role: Immuneering; Financial Interests, Institutional, Advisory Role: Seagen; Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Boehringer IngelheimBoehringer Ingelheim; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Daiichi Sankyo/UCB Japan; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Exact Sciences; Financial Interests, Personal, Advisory Role: Natera; Financial Interests, Personal, Advisory Role: Treos Bio; Financial Interests, Personal, Advisory Role: Celularity; Financial Interests, Personal, Advisory Role: SOBI; Financial Interests, Personal, Advisory Role: BeiGene; Financial Interests, Personal, Advisory Role: Foundation Medicine; Financial Interests, Personal, Other: Exelixis; Financial Interests, Institutional, Other: Merck; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Lilly; Financial Interests, Personal, Other: Pancreatic Cancer Action Network. Y. Nakamura: Financial Interests, Institutional, Research Grant: Genomedia; Financial Interests, Institutional, Research Grant: Guardant Health; Financial Interests, Institutional, Research Grant: Daiichi-Sankyo; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: Chugai. B.J. Monk: Financial Interests, Personal, Advisory Role: Abbvie; Financial Interests, Personal, Advisory Role: Advaxis; Financial Interests, Personal, Advisory Role: Agenus; Financial Interests, Personal, Advisory Role: Akeso Biopharma; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Aravive; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Asymmetric Therapeutics; Financial Interests, Personal, Advisory Role: Boston Biomedical; Financial Interests, Personal, Advisory Role: ChemoCare; Financial Interests, Personal, Advisory Role: ChemoID; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: Deciphera Pharmaceuticals; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Geistlich Pharma; Financial Interests, Personal, Advisory Role: Genmab/Seagen; Financial Interests, Personal, Advisory Role: GOG Foundation; Financial Interests, Personal, Advisory Role: ImmunoGen; Financial Interests, Personal, Advisory Role: Immunomedics; Financial Interests, Personal, Advisory Role: Incyte; Financial Interests, Personal, Advisory Role: Iovance Biotherapeutics; Financial Interests, Personal, Advisory Role: Laekna Health Care; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Mersana; Financial Interests, Personal, Advisory Role: Myriad Pharmaceuticals; Financial Interests, Personal, Advisory Role: Nucana; Financial Interests, Personal, Advisory Role: Oncomed; Financial Interests, Personal, Advisory Role: Oncoquest; Financial Interests, Personal, Advisory Role: Oncosec; Financial Interests, Personal, Advisory Role: Perthera; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Puma Biotechnology; Financial Interests, Personal, Advisory Role: Regeneron; Financial Interests, Personal, Advisory Role: Roche/Genentech; Financial Interests, Personal, Advisory Role: Senti Biosciences; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: Tarveda Therapeutics; Financial Interests, Personal, Advisory Role: Tesaro/GSK; Financial Interests, Personal, Advisory Role: Vavotar Life Sciences; Financial Interests, Personal, Advisory Role: Vascular Biogenics; Financial Interests, Personal, Advisory Role: Vigeo Therapeutics; Financial Interests, Personal, Advisory Role: Gradalis; Financial Interests, Personal, Advisory Role: Karyopharm Therapeutics; Financial Interests, Personal, Advisory Role: Sorrento Therapeutics; Financial Interests, Personal, Advisory Role: Novocure; Financial Interests, Personal, Advisory Role: Chemocare; Financial Interests, Personal, Leadership Role: US Oncology; Financial Interests, Personal, Speaker’s Bureau: Roche/Genentech; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Clovis Oncology; Financial Interests, Personal, Speaker’s Bureau: Eisai; Financial Interests, Personal, Speaker’s Bureau: Tesaro/GSK; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Other, Honoraria: Abbvie; Financial Interests, Personal, Other, Honoraria: Advaxis; Financial Interests, Personal, Other, Honoraria: Agenus; Financial Interests, Personal, Other, Honoraria: Akeso Biopharma; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: Aravive; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Asymmetric Therapeutics; Financial Interests, Personal, Other, Honoraria: Boston Biomedical; Financial Interests, Personal, Other, Honoraria: ChemoID; Financial Interests, Personal, Other, Honoraria: Clovis Oncology; Financial Interests, Personal, Other, Honoraria: Deciphera Pharmaceuticals; Financial Interests, Personal, Other, Honoraria: Eisai; Financial Interests, Personal, Other, Honoraria: Geistlich Pharma; Financial Interests, Personal, Other, Honoraria: Genmab/Seattle Genetics; Financial Interests, Personal, Other, Honoraria: ImmunoGen; Financial Interests, Personal, Other, Honoraria: Immunomedics; Financial Interests, Personal, Other, Honoraria: Incyte; Financial Interests, Personal, Other, Honoraria: Iovance Biotherapeutics; Financial Interests, Personal, Other, Honoraria: Laekna Health Care; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Mersana; Financial Interests, Personal, Other, Honoraria: Myriad Pharmaceuticals; Financial Interests, Personal, Other, Honoraria: Nucana; Financial Interests, Personal, Other, Honoraria: Oncomed; Financial Interests, Personal, Other, Honoraria: Oncoquest; Financial Interests, Personal, Other, Honoraria: Oncosec; Financial Interests, Personal, Other, Honoraria: Perthera; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Puma Biotechnology; Financial Interests, Personal, Other, Honoraria: Regeneron; Financial Interests, Personal, Other, Honoraria: Roche/Genentech; Financial Interests, Personal, Other, Honoraria: Senti Biosciences; Financial Interests, Personal, Other, Honoraria: Takeda; Financial Interests, Personal, Other, Honoraria: arveda Therapeutics; Financial Interests, Personal, Other, Honoraria: Tesaro/GSK; Financial Interests, Personal, Other, Honoraria: Vavotar Life Sciences; Financial Interests, Personal, Other, Honoraria: Vascular Biogenics; Financial Interests, Personal, Other, Honoraria: Vigeo Therapeutics; Financial Interests, Personal, Other, Honoraria: GOG Foundation; Financial Interests, Personal, Other, Honoraria: Starton Therapeutics; Financial Interests, Personal, Other, Honoraria: Elevar Therapeutics; Financial Interests, Personal, Other, Honoraria: Novocure; Financial Interests, Personal, Other, Honoraria: Iovance Biotherapeutics; Financial Interests, Personal, Other, Honoraria: Gradalis; Financial Interests, Personal, Other, Honoraria: Karyopharm Therapeutics; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Array BioPharma; Financial Interests, Institutional, Research Grant: Tesaro; Financial Interests, Institutional, Research Grant: Morphotek; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Advaxis; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Immunogen; Financial Interests, Institutional, Research Grant: Regeneron; Financial Interests, Institutional, Research Grant: Nucana. D. O'Malley: Financial Interests, Personal, Advisory Role: Janssen Oncology; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: Tesaro; Financial Interests, Personal, Advisory Role: Novocure; Financial Interests, Personal, Advisory Role: Abbvie; Financial Interests, Personal, Advisory Role: Genentech/Roche; Financial Interests, Personal, Advisory Role: OncoQuest; Financial Interests, Personal, Advisory Role: Immunogen; Financial Interests, Personal, Advisory Role: GOG Foundation; Financial Interests, Personal, Advisory Role: Translational Genomics Research; Financial Interests, Personal, Advisory Role: Agenus; Financial Interests, Personal, Advisory Role: Marker Therapeutics; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Genelux; Financial Interests, Personal, Advisory Role: Iovance Biotherapeutics; Financial Interests, Personal, Advisory Role: Ambry Genetics; Financial Interests, Personal, Advisory Role: Tarveda Therapeutics; Financial Interests, Personal, Advisory Role: Leap Therapeutics; Financial Interests, Personal, Advisory Role: Myriad Genetics; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: Regeneron; Financial Interests, Personal, Advisory Role: Sorrento Therapeutics; Financial Interests, Personal, Advisory Role: Rubius Therapeutics; Financial Interests, Personal, Advisory Role: Elevar Therapeutics; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Seagen; Financial Interests, Personal, Advisory Role: BBI Healthcare; Financial Interests, Personal, Advisory Role: Arquer Diagnostics; Financial Interests, Personal, Advisory Role: Toray Medical; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Genentech/Roche; Financial Interests, Institutional, Research Grant: Regeneron; Financial Interests, Institutional, Research Grant: Immunogen; Financial Interests, Institutional, Research Grant: Janssen Research & Development; Financial Interests, Institutional, Research Grant: Clovis Oncology; Financial Interests, Institutional, Research Grant: EMD Serono; Financial Interests, Institutional, Research Grant: Ergomed; Financial Interests, Institutional, Research Grant: Ajinomoto; Financial Interests, Institutional, Research Grant: Immunogen; Financial Interests, Institutional, Research Grant: Cerulean Pharma; Financial Interests, Institutional, Research Grant: PharmaMar; Financial Interests, Institutional, Research Grant: Array BioPharma; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Agenus; Financial Interests, Institutional, Research Grant: Tesaro; Financial Interests, Institutional, Research Grant: Tracon Pharma; Financial Interests, Institutional, Research Grant: Genmab; Financial Interests, Institutional, Research Grant: Seagen; Financial Interests, Institutional, Research Grant: Iovance Biotherapeutics; Financial Interests, Institutional, Research Grant: Leap Therapeutics; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Abbvie/Stemcentrx; Financial Interests, Institutional, Research Grant: Mersana; Financial Interests, Institutional, Research Grant: Eisai. V. Kang: Financial Interests, Personal, Full or part-time Employment: Seagen; Financial Interests, Personal, Stocks/Shares: Myovant Sciences. L.N. Walker: Financial Interests, Personal, Full or part-time Employment: Seagen; Financial Interests, Personal, Other, 39 Travel, Accommodations, Expenses: Seagen; Financial Interests, Personal, Royalties: Seagen; Financial Interests, Personal, Stocks/Shares: Seagen. T. Stinchcombe: Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Genentech/Roche; Financial Interests, Personal, Advisory Role: Foundation Medicine; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: EMD Serono; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Medtronic; Financial Interests, Personal, Advisory Role: Puma Biotechnology; Financial Interests, Personal, Advisory Role: Janssen Oncology; Financial Interests, Personal, Advisory Role: Regeneron; Financial Interests, Institutional, Research Grant: Genentech/Roche; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Advaxis; Financial Interests, Institutional, Research Grant: Regeneron; Financial Interests, Institutional, Research Grant: Seagen.