Abstract 1190TiP
Background
Patients (pts) with advanced EGFRm NSCLC have limited treatment options after progression with an EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy (PBC). HER3, a member of the human epidermal growth factor receptor family, is expressed across a variety of solid tumors and in most EGFRm NSCLC. HER3 overexpression has been associated with poor clinical outcomes, including metastatic progression and decreased relapse-free survival. HER3-DXd is a novel antibody-drug conjugate composed of a human anti-HER3 monoclonal antibody (patritumab) linked to a topoisomerase I inhibitor payload via a stable tetrapeptide-based, tumor-selective, cleavable linker. Previously reported results from this phase I trial (U31402-A-U102; NCT03260491) in heavily pretreated pts with EGFRm NSCLC (including EGFR TKI; median of 4 prior lines of therapy) showed that HER3-DXd 5.6 mg/kg every 3 weeks (Q3W) was associated with a manageable safety profile and promising efficacy (confirmed ORR by BICR, 39%; median PFS, 8.2 months [Jänne et al. Cancer Discov. 2022;12:74-89]). To extend these observations, enrollment of pts into a fourth expansion cohort has been initiated to further evaluate the pharmacokinetics (PK), safety, and efficacy of HER3-DXd from commercial manufacturing sites.
Trial design
This is a multicenter, open-label, phase I, dose-escalation/expansion study that has been amended to include cohort 4 (≈45 pts), which enrolls pts with locally advanced or metastatic EGFRm NSCLC progressing after EGFR TKI therapy and ≥1 line of PBC. EGFR-activating mutations from tumor tissue include exon 19 deletion, L858R, G719X, and L861Q; other EGFR mutations may be eligible after discussion with the sponsor. Patients are treated with HER3-DXd 5.6 mg/kg Q3W from commercial manufacturing sites, and treatment continues until disease progression, adverse events, or other discontinuation criteria are met. The primary objective of cohort 4 is to evaluate the PK of this formulation during the first treatment cycle. Secondary objectives include the evaluation of PK, safety, tolerability, immunogenicity, and efficacy.
Clinical trial identification
NCT03260491.
Editorial acknowledgement
Medical writing support was provided by Allison Lytle, PhD of Articulate Science, LLC and was funded by Daiichi Sankyo, Inc. Editorial support was provided in accordance with Good Publication Practice guidelines (ismpp.org/gpp3).
Legal entity responsible for the study
Daiichi Sankyo, Inc.
Funding
Daiichi Sankyo, Inc.
Disclosure
H.A. Yu: Financial Interests, Institutional, Funding, Research funding to my institution only: AstraZeneca, Daiichi Sankyo, Inc, Blueprint, Novartis, Pfizer, Cullinan; Financial Interests, Personal, Advisory Role, Consulting fees: AstraZeneca, Daiichi Sankyo, inc, Cullinan, C4 Therapeutics, Blueprint, Janssen, Black Diamon. F. Cantero: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc. B. Kim: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc., Merck; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo, Inc. M. Lee: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc.; Financial Interests, Personal, Stocks/Shares, Vesting in 2023/24: Daiichi Sankyo, Inc. E. Wu: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc.; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo, Inc; Financial Interests, Personal, Other, Travel, accommodations, expenses: Daiichi Sankyo, Inc. D.W. Sternberg: Financial Interests, Personal, Member of the Board of Directors: Daiichi Sankyo, Inc.; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo, Inc. P.A. Jänne: Financial Interests, Personal, Advisory Board, Consulting or advisory role: Pfizer, Boehringer Ingelheim, AstraZeneca, Merrimack, Chugai Pharma, Roche/Genentech, Loxo, Araxes Pharma, Ignyta, Lilly, Takeda, Novartis, Biocartis, Voronoi, SFJ Pharmaceuticals Group, Sanofi, Daiichi Sankyo, Inc, Silicon Therapeutics, Nuvalent, Inc., Eisai, Bayer, Syndax, AbbVie, Allorion Therapeutics, Accutar Biotech; Financial Interests, Personal, Royalties, I am a co-inventor on a DFCI owned patent on EGFR mutations licensed to Lab Corp. I receive postmarketing royalties from this invention: Labcorp; Financial Interests, Personal, Stocks/Shares, Stock or other ownership interests: Gatekeeper Pharmaceuticals, Loxo Oncology; Financial Interests, Personal, Funding, Research funding: AstraZeneca, Astellas Pharma, Daiichi Sankyo, Inc., Lilly, Boehringer Ingelheim, Puma Biotechnology, Takeda, Revolution Medicines.