Abstract 1434TiP
Background
Tucatinib (TUC), a highly selective HER2-directed TKI with minimal EGFR inhibition approved for HER2+ metastatic breast cancer, is being developed for patients (pts) with metastatic colorectal cancer (mCRC) and other GI tumors. In GEC xenograft models, dual targeting of HER2 with TUC and trastuzumab (Tras) showed superior activity to either agent alone. Interim results from the MOUNTAINEER study have shown promising activity for TUC and Tras in HER2+ mCRC.
Trial design
MOUNTAINEER-02 is a phase II/III study evaluating TUC and Tras with the 2nd-line standard of care, ramucirumab (Ram) and paclitaxel (Pac), in pts with locally-advanced unresectable or metastatic HER2+ GEC. The open-label phase II part will determine the recommended dose of Pac (60 or 80 mg/m2) combined with TUC, Tras, and Ram in 6–18 pts, to evaluate the impact of TUC on Pac metabolism, and assess the safety and activity of the regimen in Cohorts 2A and 2B (30 pts each). The randomized, double-blind, phase III part will compare the efficacy and safety of TUC and Tras (Arm 3A; ∼235 pts) vs placebo (Arm 3B; ∼235 pts), both combined with Ram and Pac, and also evaluate activity of TUC with Ram and Pac (Arm 3C; ∼30 pts). Pts receive TUC 300 mg or placebo PO BID, Tras (6 then 4 mg/kg) or placebo (IV, Days 1 and 15 of each 28-day cycle), Pac (IV, Days 1, 8, 15), and Ram (IV, Days 1 and 15). Eligible pts have received a HER2-directed antibody and 1 prior line of therapy for advanced disease, are ≥18 years, with an ECOG ≤1, and no prior Ram, anti-HER2 or anti-EGFR TKIs, HER2-directed antibody-drug conjugates, or taxanes within 12 months. Pts must be HER2+ by blood-based NGS in Cohort 2A and phase III and HER2+ by tumor tissue IHC/ISH but HER2-negative by blood-based NGS in Cohort 2B; HER2 status must be determined since progression of 1st-line therapy. The dual primary phase III endpoints are OS and PFS per investigator; confirmed ORR is a key secondary endpoint. Disease assessments per RECISTv1.1 occur q6 weeks for 36 weeks, then q9 weeks. The PK of TUC, Pac, and their metabolites will be evaluated in a subset of pts, including a cohort with gastrectomies. Enrollment is ongoing in the US with additional global sites planned.
Clinical trial identification
NCT04499924, 03 May 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
Seagen Inc.
Funding
Seagen Inc.
Disclosure
D.V. Catenacci: Financial Interests, Personal, Advisory Role: Genentech/Roche; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Taiho Pharmaceutical; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Personal, Advisory Role: Seagen; Financial Interests, Personal, Advisory Role: Daiichi Sankyo/UCB Japan; Financial Interests, Personal, Advisory Role: Zymeworks; Financial Interests, Personal, Advisory Role: Guardant Health; Financial Interests, Personal, Speaker’s Bureau: Guardant Health; Financial Interests, Personal, Speaker’s Bureau: Foundation Medicine; Financial Interests, Personal, Speaker’s Bureau: Genentech; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Speaker’s Bureau: Tempus; Financial Interests, Personal, Other, Honoraria: Genentech/Roche; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: Foundation Medicine; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Guardant Health; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb; Financial Interests, Personal, Other, Honoraria: Gritstone Oncology; Financial Interests, Personal, Other, Honoraria: Five Prime Therapeutics; Financial Interests, Personal, Other, Honoraria: Astellas Pharma; Financial Interests, Personal, Other, Honoraria: Seagen; Financial Interests, Personal, Other, Honoraria: Tempus; Financial Interests, Personal, Other, Honoraria: Pieris Pharmaceuticals; Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo/UCB Japan; Financial Interests, Personal, Other, Honoraria: Zymeworks; Financial Interests, Personal, Other, Honoraria: QED Therapeutics; Financial Interests, Personal, Other, Honoraria: Natera; Financial Interests, Personal, Other, Honoraria: Archer. J.H. Strickler: Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: AstraZenca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Other, Consulting: 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; Non-Financial Interests, Institutional, Principal Investigator, Local: AbbVie; Non-Financial Interests, Institutional, Principal Investigator, Coordinating: Amgen; Non-Financial Interests, Institutional, Principal Investigator, Local: AStar D3; Non-Financial Interests, Institutional, Principal Investigator, Local: AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator, Local: Curegenix; Non-Financial Interests, Institutional, Principal Investigator, Local: Daiichi Sankyo; Non-Financial Interests, Institutional, Principal Investigator, Coordinating: Exelixis; Non-Financial Interests, Institutional, Principal Investigator, Local: Leap Therapeutics; Non-Financial Interests, Institutional, Principal Investigator, Local: Nektar; Non-Financial Interests, Institutional, Principal Investigator, Local: Roche Genentech; Non-Financial Interests, Institutional, Principal Investigator, Local: Sanofi; Non-Financial Interests, Institutional, Principal Investigator, Coordinating: SeaGen. K. Shitara: Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Ono Pharmaceutical; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Taiho Pharmaceutical; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: AbbVie; Financial Interests, Personal, Other, Honoraria: Yakult Pharmaceutical; Financial Interests, Institutional, Research Grant: Sumitomo Dainippon Pharma; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: Chugai Pharma; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: Astellas Pharma; Financial Interests, Institutional, Research Grant: Mediscience Planning; Financial Interests, Institutional, Research Grant: Eisai. 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. Y.Y. Janjigian: Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Rgenix; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Imugene; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Zymeworks; Financial Interests, Personal, Advisory Role: Seagen; Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role: Michael J. Hennessy Associates; Financial Interests, Personal, Advisory Role: Jounce Therapeutics; Financial Interests, Personal, Advisory Role: Ono Pharmaceutical; Financial Interests, Personal, Other: Paradigm; Financial Interests, Personal, Other: Clinical Care Options; Financial Interests, Personal, Other: Axis Medical Education; Financial Interests, Personal, Other: Research to Practice; Financial Interests, Personal, Ownership Interest: Rgenix; Financial Interests, Personal, Research Grant: Boehringer Ingelheim; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Rgenix; Financial Interests, Personal, Research Grant: Bristol-Myers Squibb; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Research Grant: Lilly. A. Barzi: Financial Interests, Personal, Advisory Role: Merrion; Financial Interests, Personal, Advisory Role: bioTheranostics; Financial Interests, Personal, Advisory Role: ayer Technology System; Financial Interests, Personal, Leadership Role: Cardiff Oncology; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Merck. 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 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. H.J. Lenz: Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Personal, Other, Travel, accommodation: Merck Serono; Financial Interests, Personal, Other, Travel, accommodation: Bayer; Financial Interests, Personal, Other, Honoraria: Merck Serono; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: Isofol Medical; Financial Interests, Personal, Other, Honoraria: GlaxoSmithKline. H.C. Chung: Financial Interests, Personal, Advisory Role: Taiho Pharmaceutical; Financial Interests, Personal, Advisory Role: Celltrion; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Quintiles; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: Gloria Biosciences; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Zymeworks; Financial Interests, Personal, Advisory Role: Beigene; Financial Interests, Personal, Speaker’s Bureau: Merck Serono; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Speaker’s Bureau: Foundation medicine; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Merck Serono; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Beigene; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: Zymeworks. J. Tabernero: Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Taiho Pharmaceutical; Financial Interests, Personal, Advisory Role: Peptomyc; Financial Interests, Personal, Advisory Role: Chugai Pharma; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Seagen; Financial Interests, Personal, Advisory Role: Array BioPharma; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Genentech; Financial Interests, Personal, Advisory Role: Menarini; Financial Interests, Personal, Advisory Role: Servier; Financial Interests, Personal, Advisory Role: HalioDx; Financial Interests, Personal, Advisory Role: F. Hoffmann LaRoche; Financial Interests, Personal, Advisory Role: Mirati Therapeutics; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Role: Tessa Therapeutics; Financial Interests, Personal, Advisory Role: TheraMyc; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Samsung Bioepis; Financial Interests, Personal, Advisory Role: IQvia; Financial Interests, Personal, Advisory Role: Ikena Oncology; Financial Interests, Personal, Advisory Role: Merus; Financial Interests, Personal, Advisory Role: Neophore; Financial Interests, Personal, Advisory Role: Orion Biotechnology; Financial Interests, Personal, Advisory Role: Hutchison MediPharma; Financial Interests, Personal, Advisory Role: Avvinity; Financial Interests, Personal, Other: Imedex; Financial Interests, Personal, Other: Medscape; Financial Interests, Personal, Other: MJH Life Sciences; Financial Interests, Personal, Other: PeerView Institute for Medical Education; Financial Interests, Personal, Other: Physicans' Education Resource (PER). T. Yoshino: Financial Interests, Personal, Other, Honoraria: Chugai Pharma; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Bayer Yakuhin; Financial Interests, Personal, Other, Honoraria: Ono Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: Chugai Pharma; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Parexel; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Sanofi. S. Siena: Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Roche/Genentech; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Incyte; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Seagen; Financial Interests, Personal, Advisory Role: CheckmAb; Financial Interests, Personal, Other, Travel, accommodation, expenses: Amgen; Financial Interests, Personal, Other, Travel, accommodation, expenses: Bayer; Financial Interests, Personal, Other, Travel, accommodation, expenses: Roche; Financial Interests, Personal, Royalties: Amgen; Financial Interests, Personal, Stocks/Shares: Guardant Health; Financial Interests, Personal, Stocks/Shares: Myriad Genetics; Financial Interests, Institutional, Research Grant: MSD Oncology. J.G. Mayor: Financial Interests, Personal, Full or part-time Employment: Seagen; Financial Interests, Personal, Stocks/Shares: Seagen. M.C. Palanca-Wessels: Financial Interests, Personal, Full or part-time Employment: Seagen; Financial Interests, Personal, Stocks/Shares: Seagen. D. Xie: Financial Interests, Personal, Full or part-time Employment: Seagen; Financial Interests, Personal, Stocks/Shares: Metlife. J.L. Marshall: Financial Interests, Personal, Full or part-time Employment: Caris Life Sciences; Financial Interests, Personal, Full or part-time Employment: Indivumed; Financial Interests, Personal, Advisory Role: Genentech/Roche; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Bayer/Onyx; Financial Interests, Personal, Advisory Role: Taiho Pharmaceutical; Financial Interests, Personal, Advisory Role: Caris Life Science; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Speaker’s Bureau: Bayer/Onyx; Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: Bayer/Onyx; Financial Interests, Personal, Other, Honoraria: Taiho Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Caris Life Sciences; Financial Interests, Personal, Other, Honoraria: Merck.