L. Walker (Seattle, WA, United States of America)

Seagen Inc

Author Of 2 Presentations

 On-Demand ePoster Display

125TiP - SGNTUC-019: Phase 2 basket study of tucatinib and trastuzumab in previously treated solid tumors with HER2 alterations: HER2-mutated breast cancer cohort (Trial in Progress)

Abstract

Background

Tucatinib (TUC), a highly selective HER2-directed TKI recently approved for HER2 overexpressed/amplified (HER2+) metastatic breast cancer (BC), on the basis of a statistically significant and clinically meaningful PFS, OS, and ORR benefit for the addition of TUC to trastuzumab (Tras) and capecitabine. TUC is being developed as a novel therapy for patients (pts) with metastatic BC, CRC, and gastric cancer. In xenograft models of HER2+ and HER2-mutated (HER2-mut) tumors, dual targeting of HER2 with TUC and Tras showed superior activity to either agent alone. The SGNTUC-019 basket study is evaluating TUC in combination with Tras in pts with HER2+ or HER2-mut solid tumors, including a cohort of pts with locally advanced unresectable or metastatic (LAUM) HER2-mut BC.

Trial design

SGNTUC-019 is a multi-cohort, open-label, international phase II study evaluating pts with previously treated solid tumors displaying HER2 overexpression/amplification or activating mutations. Eligible pts must have HER2+ or HER2-mut LAUM solid tumors, with progression on or after the last systemic therapy for advanced disease, be ≥18 years old, with ECOG PS ≤1, adequate hepatic, hematological, renal, and cardiac function, and no prior HER2-directed therapy. For eligibility, HER2-mut can be demonstrated in a prior or on-study NGS assay of ctDNA or prior tissue NGS assay. The BC cohort will enroll 30 response-evaluable pts with HER2-mut disease. Pts with HER2+ BC will not be enrolled. The primary objective is antitumor activity in each cohort, with confirmed ORR as primary endpoint, and disease control rate, duration of response, PFS, and OS as secondary endpoints. Pts will receive TUC 300 mg PO BID and Tras 8 mg/kg IV on Cycle (C) 1 Day (D) 1 and 6 mg/kg q21 days from C2 D1. Hormone receptor positive BC pts will also receive fulvestrant 500 mg IM every 4 weeks and C1 D15. Disease assessments per RECIST 1.1 are q6 weeks for 24 weeks, then q12 weeks. Pts with brain metastases may be eligible; pts in the BC and lung cancer cohorts will undergo baseline brain MRI. Quality of life will be evaluated q2 cycle using EQ-5D-5L. Sites are open in the US; EU and Asia will be opened. Enrollment began in Dec 2020.

Clinical trial identification

NCT04579380.

Editorial acknowledgement

William Sutherland, freelance, assisted in the preparation of this abstract.

Legal entity responsible for the study

Seagen Inc.

Funding

Seagen Inc.

Disclosure

A. Okines: Research grant/Funding (self): Roche; Advisory/Consultancy: Roche; Travel/Accommodation/Expenses: Leo Pharmaceuticals; Honoraria (self): Seagen; Advisory/Consultancy: Seagen; Research grant/Funding (self): Pfizer; Travel/Accommodation/Expenses: AstraZeneca/Daiichi Sankyo; Honoraria (self): AstraZeneca/Daiichi Sankyo. V. Kang: Full/Part-time employment: Seagen; Shareholder/Stockholder/Stock options: Myovant Sciences. L.N. Walker: Full/Part-time employment: Seagen; Travel/Accommodation/Expenses: Seagen; Licensing/Royalties: Seagen; Shareholder/Stockholder/Stock options: Seagen. P.R. Pohlmann: Advisory/Consultancy, Leadership role, Shareholder/Stockholder/Stock options: Immunonet Biosciences; Advisory/Consultancy: Perthera; Advisory/Consultancy: Sirtex; Advisory/Consultancy: Xcenda; Advisory/Consultancy: CARIS; Advisory/Consultancy: OncoPlex Diagnostics; Advisory/Consultancy: Heron; Advisory/Consultancy: Puma; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): Pieris; Advisory/Consultancy, Research grant/Funding (institution): Seagen; Research grant/Funding (institution): Bolt; Research grant/Funding (institution): Byondis.

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126TiP - HER2CLIMB-02: Tucatinib or placebo with T-DM1 for unresectable locally-advanced or metastatic HER2+ breast cancer

Abstract

Background

Tucatinib (TUC), an oral tyrosine kinase inhibitor (TKI) highly selective for HER2 with minimal inhibition of EGFR, is approved in the US, Canada, Switzerland, Australia, and Singapore for combined treatment with trastuzumab (Tras) and capecitabine for patients with HER2+ metastatic breast cancer (MBC), including patients with brain metastases (BM) who received 1 or more prior anti-HER2-based regimens in the metastatic setting. Ado-Tras emtansine (T-DM1), approved for treatment of HER2+ MBC after Tras and a taxane, has improved progression-free survival (PFS) and overall survival (OS). Further improvements are needed, including in patients with active BM. A phase Ib trial evaluated TUC+T-DM1 in 50 patients with HER2+ MBC who received prior treatment with Tras and a taxane; 60% of patients had BM at baseline (Borges 2018). Common adverse events, mostly Grade 1/2, were nausea (72%), diarrhea (60%), and fatigue (56%). Median PFS was 8.2 months and objective response rate (ORR) in patients with measurable disease (n=34) was 47%. Brain specific response rate (RECIST v1.1) in patients with measurable BM (n=14) was 36%. This encouraging clinical activity, including in patients with BM, provides rationale to evaluate TUC+T-DM1.

Trial design

HER2CLIMB-02 is a randomized, double-blind, placebo-controlled, phase III study enrolling patients with centrally confirmed HER2+ unresectable locally-advanced or MBC previously treated with Tras and taxane. Patients must have ECOG ≤1. Approximately 460 patients will be randomized 1:1 for 21-day cycles of TUC (300 mg PO BID) or placebo with T-DM1 (3.6 mg/kg IV). Prior treatment with investigational anti-HER2 agent, anti-EGFR agent, or HER2 TKI is not permitted. Prior pertuzumab treatment is permitted. Baseline brain MRIs are required; patients with stable, progressing, or untreated BM may be eligible. Treatment response assessments per RECISTv1.1 occur every 6 weeks for the first 24 weeks, and then every 9 weeks. Primary endpoint is PFS per investigator assessment, with OS and ORR as key secondary endpoints. Enrollment is ongoing in the US, Canada, EU, Japan, South Korea, Australia, and Israel, and is planned for Singapore.

Clinical trial identification

NCT03975647.

Editorial acknowledgement

Editorial assistance was provided by Craig Bolte of MMS Holdings.

Legal entity responsible for the study

Seagen Inc.

Funding

Seagen Inc.

Disclosure

S.A. Hurvitz: Research grant/Funding (institution): Ambrx, Amgen; Research grant/Funding (institution): AstraZeneca, Arvinas; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Genentech/Roche, Bayer; Research grant/Funding (institution): Gilead, Immunomedics; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution), Travel/Accommodation/Expenses: Eli Lilly; Research grant/Funding (institution): Macrogenetics, Novartis; Research grant/Funding (institution): Pfizer, Obi Pharma; Research grant/Funding (institution): Pieris, Puma; Research grant/Funding (institution): Radius, Sanofi; Research grant/Funding (institution): Seagen Inc.; Research grant/Funding (institution): Dignitana, Zymeworks; Research grant/Funding (institution): Phoenix Molecular Designs, Ltd.; Shareholder/Stockholder/Stock options: Nk Max. N. Harbeck: Honoraria (self): AstraZeneca; Honoraria (self): Daiichi Sankyo; Honoraria (self): Eli Lilly; Honoraria (self): MSD Pharmaceuticals; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): Sandoz/Hexal; Honoraria (self): Seagen Inc. L. Vahdat: Advisory/Consultancy, Research grant/Funding (institution): Arvinas; Advisory/Consultancy: Roche; Advisory/Consultancy: Berg Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai Co., Ltd.; Advisory/Consultancy, Research grant/Funding (institution): Polyphor Pharma; Advisory/Consultancy, Travel/Accommodation/Expenses: Seagen Inc.; Research grant/Funding (institution): Genentech/Roche; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Oncotherapy Biosciences. S.M. Tolaney: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Daiichi Sankyo, OncoPep; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly, Eisai; Advisory/Consultancy: G1 Therapeutics, Outcomes4Me; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): Immunomedics; Advisory/Consultancy: Kyowa Kirin, Silverback Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): NanoString; Advisory/Consultancy, Research grant/Funding (institution): Nektar, Seagen; Advisory/Consultancy, Research grant/Funding (institution): Novartis, Pfizer; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Cyclacel, Odonate; Advisory/Consultancy: Puma Therapeutics, Sanofi; Advisory/Consultancy: Celldex, Paxman, AbbVie; Advisory/Consultancy: Samsung Bioepsis Inc. S. Loi: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Aduro Biotech; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): Seagen Inc; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Puma Biotech. N. Masuda: Honoraria (self), Research grant/Funding (institution): Chugai Pharma; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Honoraria (self), Research grant/Funding (institution): Eisai; Honoraria (self): Takeda; Research grant/Funding (institution): Kyowa-Kirin; Research grant/Funding (institution): MSD Pharma; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Nippon-Kayaku; Research grant/Funding (institution): Daiichi Sankyo. J. O'Shaughnessy: Advisory/Consultancy: AbbVie, Agendia; Advisory/Consultancy: Amgen Biotech; Advisory/Consultancy: Aptitude Health; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Celgene, Eisai; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy: Genentech; Advisory/Consultancy: Immunomedics; Advisory/Consultancy: Ipsen Biopharma; Advisory/Consultancy: Jounce Therapeutics; Advisory/Consultancy: Eli Lilly, Merck; Advisory/Consultancy: Myriad, Novartis; Advisory/Consultancy: Ondonate Therapeutics; Advisory/Consultancy: Pfizer, Puma Biotech; Advisory/Consultancy: prIME Oncology; Advisory/Consultancy: Roche, Seagen Inc; Advisory/Consultancy: Syndax Pharmaceuticals. D. Xie: Full/Part-time employment: Seagen Inc. L.N. Walker: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Seagen Inc. E. Rustia: Shareholder/Stockholder/Stock options, Full/Part-time employment: Seagen Inc. V. Borges: Advisory/Consultancy, Research grant/Funding (institution): Seagen Inc; Research grant/Funding (institution): Abbot/AbbVie; Research grant/Funding (institution): Millenium. All other authors have declared no conflicts of interest.

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