Abstract 1437TiP
Background
Human epidermal growth factor receptor 2 (HER2) gene amplification or protein overexpression (HER2+) occurs in many gastrointestinal (GI) cancers, and HER2-targeting strategies are improving outcomes. Tucatinib (TUC), approved in multiple regions for HER2+ metastatic breast cancer, is a highly selective HER2-directed tyrosine kinase inhibitor with minimal EGFR inhibition. In patient (pt) derived xenograft models of HER2+ tumors, TUC + trastuzumab (T) showed superior anti-tumor activity compared with either agent alone (Kulukian 2020). Interim results from the MOUNTAINEER study showed promising activity for TUC + T in HER2+ metastatic colorectal cancer (CRC). In 23 response-evaluable pts, an objective response rate of 52.2% (12 partial responses), median duration of response of 10.4 months, median progression-free survival of 8.1 months, and median overall survival of 18.7 months was observed. The SGNTUC-024 (NCT04430738) study will evaluate TUC + T + oxaliplatin-based chemotherapy (OX) in pts with unresectable or metastatic GI cancers.
Trial design
SGNTUC-024 is an open-label, dose escalation and expansion phase Ib/II trial. The initial phase Ib cohort enrolled pts with gastric, esophageal, and gastroesophageal junction (GEJ) adenocarcinoma, cholangiocarcinoma, gallbladder carcinoma, and CRC to receive TUC (150 mg oral [PO] twice daily [BID]) + T + FOLFOX (fluorouracil, leucovorin, oxaliplatin). Subsequent phase Ib cohorts will receive TUC (300 mg PO BID) + T + either FOLFOX or CAPOX (capecitabine, oxaliplatin). Once a safe dose is defined in phase Ib, phase II will enroll pts with gastric, esophageal, and GEJ adenocarcinomas (TUC + T + either FOLFOX or CAPOX) and pts with CRC (TUC + T + FOLFOX). Phase II will expand the assessment of safety and tolerability and assess efficacy of TUC + T + OX. Pts must be eligible for an OX regimen as standard-of-care. Pts with irradiated or resected central nervous system (CNS) lesions may enroll. Pts with known active CNS lesions may be eligible for phase II. The phase Ib portion of the trial (300 mg TUC PO BID) is currently enrolling in the US.
Clinical trial identification
NCT04430738.
Editorial acknowledgement
Editorial/writing assistance was provided by Michelle Ubowski and Aulma Parker of Seagen Inc.
Legal entity responsible for the study
Seagen Inc.
Funding
Seagen Inc.
Disclosure
H. Park: Financial Interests, Institutional, Principal Investigator: Ambryx; Financial Interests, Institutional, Principal Investigator: Amgen; Financial Interests, Institutional, Principal Investigator: Aprea Therapeutics AB; Financial Interests, Institutional, Principal Investigator: Array BioPharma; Financial Interests, Institutional, Principal Investigator: Bayer; Financial Interests, Institutional, Principal Investigator: BeiGene; Financial Interests, Institutional, Principal Investigator: BJ Bioscience; Financial Interests, Institutional, Principal Investigator: Bristol-Myers Squibb; Financial Interests, Institutional, Principal Investigator: Daiichi Pharmaceuticals; Financial Interests, Institutional, Principal Investigator: Eli Lilly; Financial Interests, Institutional, Principal Investigator: Elicio Therapeutics; Financial Interests, Institutional, Principal Investigator: EMD Serono; Financial Interests, Institutional, Principal Investigator: Genentech; Financial Interests, Institutional, Principal Investigator: Gilead Sciences; Financial Interests, Institutional, Principal Investigator: GlaxoSmithKline; Financial Interests, Institutional, Principal Investigator: Gossamer Bio; Financial Interests, Institutional, Principal Investigator: Hoffman-LaRoche; Financial Interests, Institutional, Principal Investigator: Hutchison MediPharma; Financial Interests, Institutional, Principal Investigator: ImmuneOncia Therpeutics; Financial Interests, Institutional, Principal Investigator: Incyte; Financial Interests, Institutional, Principal Investigator: Jounce Therapeutics; Financial Interests, Institutional, Principal Investigator: Mabspace Biosciences; Financial Interests, Institutional, Principal Investigator: MacroGenics; Financial Interests, Institutional, Principal Investigator: Medimmune; Financial Interests, Institutional, Principal Investigator: Medivation; Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Institutional, Principal Investigator: Millennium; Financial Interests, Institutional, Principal Investigator: Mirati Therapeutics; Financial Interests, Institutional, Principal Investigator: Novartis Pharmaceuticals; Financial Interests, Institutional, Principal Investigator: Oncologie; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Principal Investigator: PsiOxus Therapeutics; Financial Interests, Institutional, Principal Investigator: Puma Biotechnology; Financial Interests, Institutional, Principal Investigator: Regeneron Pharmaceuticals; Financial Interests, Institutional, Principal Investigator: Seagen Inc.; Financial Interests, Institutional, Principal Investigator: Synermore Biologics; Financial Interests, Institutional, Principal Investigator: Taiho Pharmaceutical; Financial Interests, Institutional, Principal Investigator: TopAlliance Biosciences; Financial Interests, Institutional, Principal Investigator: Turning Point Therapeutics; Financial Interests, Institutional, Principal Investigator: Vedanta Bioscience; Financial Interests, Institutional, Principal Investigator: Vertex Pharmaceuticals; Financial Interests, Institutional, Principal Investigator: Xencor Inc. T. Bekaii-Saab: Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Other, DSMB: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Beigene; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Celularity; Financial Interests, Personal, Advisory Board: Daichi Sankyo; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Exact Science; Financial Interests, Personal, Other, DSMB: Exelixis; Financial Interests, Personal, Advisory Board: Foundation Medicine; Financial Interests, Institutional, Advisory Board: Genentech; Financial Interests, Institutional, Advisory Board: Incyte; Financial Interests, Institutional, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Other, DSMB: Lilly; Financial Interests, Institutional, Other, DSMB: Merck; Financial Interests, Personal, Advisory Board: Natera; Financial Interests, Personal, Other, DSMC: PanCAN; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: Seagen Inc.; Financial Interests, Personal, Advisory Board: Sobi; Financial Interests, Personal, Advisory Board: Xilis; Financial Interests, Institutional, Research Grant: Abgenomics; Financial Interests, Institutional, Research Grant: Agios; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Arcus; Financial Interests, Institutional, Research Grant: Arys; Financial Interests, Institutional, Research Grant: Atreca; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Principal Investigator: Boston Biomedical; Financial Interests, Institutional, Research Grant: Celgene; Financial Interests, Institutional, Research Grant: Clovis; Financial Interests, Institutional, Principal Investigator: Incyte; Financial Interests, Institutional, Research Grant: Ipsen; Financial Interests, Institutional, Research Grant: Merus; Financial Interests, Institutional, Research Grant: Mirati; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Other, Steering Committee Member: Seagen Inc.; Financial Interests, Personal and Institutional, Advisory Role: Imugene; Financial Interests, Personal and Institutional, Advisory Role: Sun Biopharma. S.S. Kim: Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Advisory Board: Merck; Non-Financial Interests, Personal and Institutional, Sponsor/Funding: GSK; Non-Financial Interests, Personal and Institutional, Sponsor/Funding, Clinical trial funding: Merck. S. Kamath: Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Role: Tempus. M.J. Pishvaian: Financial Interests, Personal, Advisory Board, Ad hoc advisory boards: AstraZeneca; Financial Interests, Personal, Advisory Board, Ad hoc advisory boards: Merck; Financial Interests, Personal, Stocks/Shares: Perthera; Financial Interests, Institutional, Principal Investigator, Local PI of Sponsored trial; funding to institution only: Seagen Inc.; Non-Financial Interests, Institutional, Principal Investigator, Study co-chair of SWOG/Alliance trial of olaparib + pembrolizumab: Merck; Non-Financial Interests, Institutional, Principal Investigator, Study co-chair of an ACCRU trial of encorafenib + binimetinib for BRAF mutated pancreatic cancer: Pfizer; Non-Financial Interests, Personal, Other, Consultant, and co-author on papers: Perthera, Inc. J. Ford: Non-Financial Interests, Institutional, Principal Investigator, Stanford PI on POLO trial: AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator, Stanford PI on MyPathway trial: Genetech; Non-Financial Interests, Institutional, Principal Investigator, Stanford PI on Talozoparib trial: Pfizer; Non-Financial Interests, Institutional, Principal Investigator, Stanford PI on Summit trial: PUMA; Non-Financial Interests, Institutional, Principal Investigator, Stanford PI on Tucatinib trials: Seagen Inc. D.B. Zhen: Financial Interests, Personal, Advisory Board: QED Therapeutics. J. Mayor: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Stocks/Shares: Seagen Inc. C. Lux: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Stocks/Shares: Seagen Inc. Q. Tan: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Stocks/Shares: Seagen Inc. J.H. Strickler: Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Other: Mereo; Financial Interests, Personal, Advisory Board: Natera; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Advisory Board: Viatris; Financial Interests, Institutional, Principal Investigator: AbbVie; Financial Interests, Institutional, Principal Investigator: Amgen; Financial Interests, Institutional, Principal Investigator: AStar D3; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Curegenix; Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo; Financial Interests, Institutional, Principal Investigator: Exelixis; Financial Interests, Institutional, Principal Investigator: Leap Therapeutics; Financial Interests, Institutional, Principal Investigator: Nektar Therapeutics; Financial Interests, Institutional, Principal Investigator: Roche Genentech; Financial Interests, Institutional, Principal Investigator: Sanofi; Financial Interests, Institutional, Principal Investigator: Seagen.