Abstract 75TiP
Background
There is an unmet therapeutic need for patients with NSCLC who have disease progression after standard of care treatment. FRα is highly expressed on tumor cells in patients with NSCLC AC. FZEC is an ADC comprised of the humanized anti-FRα monoclonal antibody farletuzumab and the microtubule dynamics inhibitor eribulin. A phase I study in Japan (NCT03386942) demonstrated the antitumor activity of FZEC across multiple tumor types, including NSCLC, and identified interstitial lung disease (ILD) as an adverse event of interest (Shimizu 2021). This global, multicenter, phase II trial across 6 countries aims to evaluate the safety, efficacy, and optimal dose of FZEC in patients with previously treated metastatic NSCLC AC.
Trial design
Approximately 60 adults with advanced/metastatic NSCLC either without genetic alterations who have received ≥ 1 line of platinum-doublet chemotherapy and anti–PD-1/PD-L1 therapy or with genetic alternations who have received 1 targeted therapy and ≤ 3 lines of systemic therapy will be enrolled. Patients will be randomized 1:1 to receive FZEC Q3W at doses of 33 mg/m2 (Arm A) or 25 mg/m2 (Arm B). A pharmacokinetics model demonstrated that body surface area (BSA)–based dosing is predicted to reduce the risk of exposure-driven ILD (Hayato 2022). The primary objectives are to assess incidence of treatment-related adverse events leading to study discontinuation and investigator-assessed objective response rate by RECIST v1.1. Primary analysis will be performed after ≥ 6 months follow-up. Safety follow-up will occur 30 days after last dose, with survival follow-up every 3 months from safety follow-up visit until last participant has completed 2 years of follow-up. Measures to enhance early detection of ILD have been introduced and steps to potentially reduce the occurrence of severe ILD include implementation of BSA–based dosing, lung-specific eligibility criteria, revised and stringent ILD management criteria, and ILD training for relevant study personnel. *Formerly MORAb-202.
Clinical trial identification
NCT05577715.
Editorial acknowledgement
Editorial support was provided by Emily Motola, PharmD, and Richard McDonald of Spark Medica Inc.
Legal entity responsible for the study
Bristol Myers Squibb.
Funding
Bristol Myers Squibb.
Disclosure
D. Planchard: Financial Interests, Personal, Advisory Role, Consultancy fees: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, Roche, Janssen, AbbVie; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, Roche, Janssen, AbbVie; Financial Interests, Personal, Principal Investigator, Principal or Co-investigator: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo, Janssen, AbbVie; Financial Interests, Personal, Other, Travel/accommodation support: AstraZeneca, Roche, Novartis, Pfizer. L. Paz-Ares: Financial Interests, Personal and Institutional, Funding, Grants: MSD, AstraZeneca, Pfizer, and Bristol Myers Squibb and consulting fees from Eli Lilly, MSD, Roche, PharmaMar, Merck KGaA (Darmstadt, Germany), AstraZeneca, Novartis, Servier, Amgen, Pfizer, Sanofi, Bayer, BMS, Mirati, GlaxoSmithKline, Janssen, Takeda; Financial Interests, Personal, Other, Honoraria: Roche/Genentech, Eli Lilly, Pfizer, Bristol Myers Squibb, MSD, AstraZeneca, Merck Serono, PharmaMar, Novartis, Celgene, Amgen, Mirati, AbbVie; Financial Interests, Personal, Other, Meeting attendance/travel: Roche, AstraZeneca, MSD, Bristol Myers Squibb, Eli Lilly, Pfizer; Financial Interests, Personal, Advisory Board, Data safety monitoring, advisory board: Altum Sequencing and Genomica; Financial Interests, Personal, Advisory Board, External board: Genomica; Financial Interests, Personal, Ownership Interest, Founding partner: Altum Sequencing; Financial Interests, Personal, Other, Other financial interests: Novartis, Ipsen, Pfizer, Servier, Sanofi, Roche, Amgen, and Merck. A. Spira: Financial Interests, Personal, Stocks/Shares: Eli Lilly; Financial Interests, Personal, Other, Honoraria: CytomX Therapeutics, AstraZeneca/MedImmune, Merck, Takeda, Amgen, Janssen Oncology, Novartis, Bristol Myers Squibb, Bayer, Inctye, Amgen, Novartis, Mirati Therapeutics, Gritstone Oncology, Gritstone Bio, Jazz Pharmaceuticals, Takeda, Janssen Research & De; Financial Interests, Institutional, Other, Honoraria: Array BioPharma, AstraZeneca/MedImmune, Merck, Bristol Myers Squibb, and Blueprint Medicines; Financial Interests, Personal, Funding: LAM Therapeutics and Regeneron; Financial Interests, Institutional, Funding: Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, LAM Therapeutics, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol Myers Squibb, Loxo, Arch Therap. E. Felip: Financial Interests, Institutional, Funding: Merck; Financial Interests, Personal, Other, Consulting fees: Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Pfizer, Sanofi, Takeda, Bergenbio; Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Janssen, Medica Trends, Medscape, Merck Serono, Merck Sharp & Dohme, Peervoice, Pfizer, Sanofi, Takeda, Touch Oncology; Financial Interests, Personal, Member of the Board of Directors, Independent board member: Grifols. S. McCune: Financial Interests, Personal, Other, Consulting fees, honoraria: Bristol Myers Squibb. T. Cascella: Financial Interests, Personal, Full or part-time Employment: Myers Squibb; Financial Interests, Personal, Stocks/Shares: Myers Squibb; Financial Interests, Personal, Other, Meeting attendance support: Myers Squibb. J. Dennie: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. P. Bhagavatheeswaran: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. C. Dumitru: Financial Interests, Personal, Full or part-time Employment: Eisai Inc. H. Borghaei: Financial Interests, Personal, Funding: Bristol Myers Squibb, Eli Lilly, and Amgen; Financial Interests, Personal, Advisory Board, Also consulting: Bristol Myers Squibb, Eli Lilly, Genentech, Pfizer, Merck, EMD-Serono, Boehringer Ingelheim, AstraZeneca, Novartis, Genmab, Regeneron, BioNTech, Amgen, Axiom, PharmaMar, Takeda, Mirati, Daiichi Sankyo, Guardant, Natera, Oncocyte, BeiGene, iTEO, Jazz Pharmaceuticals, Janssen, Da Vo; Financial Interests, Personal, Other, Honoraria: Amgen, Pfizer, Daiichi Sankyo, and Regeneron; Financial Interests, Personal, Other, Meeting/travel support: Amgen, Bristol Myers Squibb, Merck, Eli Lilly, EMD-Serano, Genentech, and Regenero; Financial Interests, Personal, Advisory Board, Data safety monitoring board: University of Pennsylvania CAR T program, Takeda, Incyte, and Novartis; Financial Interests, Personal, Other, Medical writing support: Bristol Myers Squibb, Amgen, and AstraZeneca; Financial Interests, Personal, Stocks/Shares: Sonnetbio, Inspirna, Rgenix, and Nucleai.