The prognosis of locally-advanced unresectable or metastatic (LA/M) cervical and uterine cancer remains poor, with HER2 alterations occurring in 0.5-21% of cervical cancers and 2-80% of uterine cancers, respectively. Tucatinib (TUC), a highly selective HER2 directed TKI, is approved in combination with trastuzumab (Tras) and capecitabine in multiple regions for HER2+ metastatic breast cancer and is being investigated in other HER2+ cancers, including LA/M cervical and uterine cancer. SGNTUC-019 (NCT04579380) is an open-label, international phase II basket study evaluating TUC and Tras in adult patients (pts) with LA/M HER2+ or HER2-mutated solid tumors.
SGNTUC-019 will evaluate TUC and Tras in pts with previously treated, LA/M solid tumors that display HER2 overexpression/amplification or activating mutations, including HER2+ cervical and uterine cancer cohorts. Pts will receive TUC 300 mg PO BID and Tras 8 mg/kg IV on Cycle 1 Day 1 and 6 mg/kg q21 days from Cycle 2 Day 1. HER2+ cervical and uterine cancer cohorts will enroll 12 pts each with potential for expansion up to 30 pts. Pts with HER2-mutated cervical, uterine, and other gynecologic cancers may enroll in a pooled cohort of 30 pts with HER2-mutated solid tumor types. Eligible pts must have progressed on or after their last systemic therapy, with prior platinum-based chemotherapy ± bevacizumab required in pts with metastatic cervical cancer. Pts must have ECOG PS ≤1, adequate organ function, and have not received HER2-directed therapy; pts with uterine serous carcinoma may have received prior Tras. HER2 alterations can be demonstrated by HER2 overexpression/amplification in tumor tissue by prior IHC/ISH, or by HER2 amplification/mutation in a prior or on-study NGS assay of ctDNA or prior tissue NGS assay. The primary endpoint is confirmed ORR per investigator. DCR, DOR, PFS, OS, safety, and PK are secondary endpoints. Disease assessments per RECIST 1.1 will occur q6 weeks for 24 weeks, then q12 weeks. QoL will be evaluated q2 cycles using EQ-5D-5L. Enrollment is now open in Europe, the US, and Asia Pacific.
NCT04579380.
Seagen Inc., Bothell, WA, USA in collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Ind., Kenilworth, NJ, USA.
Seagen Inc., Bothell, WA, USA in collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Ind., Kenilworth, NJ, USA.
D. O'Malley: Financial Interests, Personal and Institutional, Research Grant, Consultancy: AbbVie; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Agenus; Financial Interests, Personal, Other, Consultancy: Ambry; Financial Interests, Personal, Other, Consultancy: Arquer; Financial Interests, Personal and Institutional, Research Grant, Consultancy: AstraZeneca; Financial Interests, Personal, Other, Consultancy: Celsion; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Clovis; Financial Interests, Personal, Other, Consultancy: Corcept; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Eisai; Financial Interests, Personal, Other, Consultancy: Elevar; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Genentech/Roche; Financial Interests, Personal and Institutional, Research Grant, Consultancy: GOG Fnd; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Immunogen; Financial Interests, Personal and Institutional, Research Grant: Inc. Research; Financial Interests, Personal and Institutional, Research Grant: InVentiv Health; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Iovance; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Janssen; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Johnson & Johnson; Financial Interests, Personal, Other, Consultancy: Merck; Financial Interests, Personal and Institutional, Research Grant, Consultancy: Mersana; Financial Interests, Personal, Other, Consultancy: Myriad; Financial Interests, Personal, Other, Consultancy: Novartis Novocure; Financial Interests, Personal, Other, Consultancy: Regeneron; Financial Interests, Personal, Other, Consultancy: Roche; Financial Interests, Personal, Other, Consultancy: Rubis; Financial Interests, Personal, Other, Consultancy: SDPOnc; Financial Interests, Personal, Other, Consultancy: Seagen Inc.; Financial Interests, Personal, Research Grant, Consultancy: Amgen; Financial Interests, Personal, Other, Consultancy: Inxmed; Financial Interests, Personal and Institutional, Research Grant: Ajinomoto; Financial Interests, Personal and Institutional, Research Grant: Array; Financial Interests, Personal and Institutional, Research Grant: BMS; Financial Interests, Personal and Institutional, Research Grant: Cerulean; Financial Interests, Personal and Institutional, Research Grant: EMD Serono; Financial Interests, Personal and Institutional, Research Grant: Ergomed; Financial Interests, Personal and Institutional, Research Grant: GenMab; Financial Interests, Personal and Institutional, Research Grant: Ludwig Cancer Research; Financial Interests, Personal and Institutional, Research Grant: Merck; Financial Interests, Personal and Institutional, Research Grant: New Mexico CCA; Financial Interests, Personal and Institutional, Research Grant: Novocure; Financial Interests, Personal and Institutional, Research Grant: PRA Int'l; Financial Interests, Personal and Institutional, Research Grant: Regeneron; Financial Interests, Personal and Institutional, Research Grant: SDPOnc; Financial Interests, Personal and Institutional, Research Grant: Seagen Inc.; Financial Interests, Personal and Institutional, Research Grant: Serono; Financial Interests, Personal and Institutional, Research Grant: Stemcentrx; Financial Interests, Personal and Institutional, Research Grant: Tarveda; Financial Interests, Personal and Institutional, Research Grant: Tesaro/GSK; Financial Interests, Personal and Institutional, Research Grant: Tracon Pharma; Financial Interests, Personal and Institutional, Research Grant: VentiRx; Financial Interests, Personal and Institutional, Research Grant: Yale University; Financial Interests, Personal, Invited Speaker: Sorrento; Financial Interests, Personal, Other, Consultancy: Takeda; Financial Interests, Personal, Other, Consultancy: Tesaro/GSK; Financial Interests, Personal, Other, Consultancy: Toray. F.J. Jin: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Ownership Interest: Merck; Financial Interests, Personal, Other, Travel Expenses: Merck. J.D. Ramos: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Ownership Interest: Seagen Inc. Q. Tan: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Ownership Interest: Seagen Inc.; Financial Interests, Personal, Other, Travel Expenses: Seagen Inc. B.J. Monk: Financial Interests, Personal, Other, Consultant: Agenus; Financial Interests, Personal, Other, Consultant: Akeso Bio; Financial Interests, Personal, Other, Consultant: Amgen; Financial Interests, Personal, Other, Consultant: Aravive; Financial Interests, Personal, Other, Speaker/Consultant: AstraZeneca; Financial Interests, Personal, Other, Consultant: Bayer; Financial Interests, Personal, Other, Speaker/Consultant: Clovis; Financial Interests, Personal, Other, Speaker/Consultant: Eisai; Financial Interests, Personal, Other, Consultant: Elevar; Financial Interests, Personal, Other, Consultant: EMD Merck; Financial Interests, Personal, Other, Consultant: Genmab/Seagen; Financial Interests, Personal, Other, Consultant: GOG Foundation; Financial Interests, Personal, Other, Consultant: Gradalis; Financial Interests, Personal, Other, Consultant: ImmunoGen; Financial Interests, Personal, Other, Consultant: Karyopharm; Financial Interests, Personal, Other, Consultant: Iovance; Financial Interests, Personal, Other, Consultant: Macrogenics; Financial Interests, Personal, Other, Speaker/Consultant: Merck; Financial Interests, Personal, Other, Consultant: Mersana; Financial Interests, Personal, Other, Honorarium: Novartis; Financial Interests, Personal, Other, Consultant: Novocure; Financial Interests, Personal, Other, Consultant: Myriad; Financial Interests, Personal, Other, Consultant: OncoC4; Financial Interests, Personal, Other, Consultant: Pieris; Financial Interests, Personal, Other, Consultant: Pfizer; Financial Interests, Personal, Other, Consultant: Puma; Financial Interests, Personal, Other, Consultant: Regeneron; Financial Interests, Personal, Other, Speaker/Consultant: Roche/Genentech; Financial Interests, Personal, Other, Consultant: Sorrento; Financial Interests, Personal, Other, Speaker/Consultant: Tesaro/GSK; Financial Interests, Personal, Other, Consultant & Investigator: US Oncology Research; Financial Interests, Personal, Other, Consultant: VBL.