Abstract 147P
Background
Tarlatamab (AMG 757) binds DLL3 on SCLC cells and CD3 on T cells leading to T cell-mediated tumor lysis. Updated phase 1 tarlatamab data in relapsed/refractory SCLC showed an ORR of 23%, median DOR of 13 months, and an acceptable safety profile with cytokine release syndrome (CRS) as the most common treatment-related (TRAE).1 Here, we describe clinical CRS seen with tarlatamab and explore associations between cytokine levels and CRS in cycle 1 (C1)-where CRS mostly occurs.
Methods
Tarlatamab (0.003–100.0 mg) was given intravenously every 2 weeks ± step dosing in patients (pts) with SCLC progressing after ≥1 platinum-based regimen. Safety/efficacy were evaluated as previously described.1 Serum was drawn at time points up to 24 hours (hrs) after first dose from pts receiving ≥1 mg initial dose and up to 100 mg in subsequent doses in C1. Peak level and elevation speed were evaluated for a panel of soluble factors in pts with CRS vs no CRS in C1.
Results
By 15 June 2022, 106 pts had received ≥1 dose tarlatamab with median follow-up time of 8.5 months (range, 0.2–30.7). Median treatment duration was 11.6 weeks (range, 0.1–80.0). TRAEs occurred in 97 pts (92%) and grade (gr) ≥ 3 in 33 pts (31%). CRS occurred in 56 pts (53%) with maximum gr1 in 41 pts and gr3 in 1 (1.0%), and 8 pts received tocilizumab for CRS. Most CRS events were in C1 (55 pts in C1, 5 pts in C2+). CRS had median onset of 17.5 hrs (in pts with both date and hr of onset data), was transient (median duration, 3 days), and resolved in all cases. While initial tarlatamab infusion is characterized by immune activation and inflammatory cytokine induction, among biomarker-evaluable pts (N=86), those with any grade CRS in C1 (n=45 or 46) showed trends in increased peak levels of IL-6, IL-8, IL-10, and TNF-α by 24 hrs after first dose vs those without (n=40).
Conclusions
Prior results from this study show manageable safety and promising efficacy of tarlatamab in pts with heavily pretreated SCLC. CRS is not unexpected based on tarlatamab’s mechanism of action, is associated with rises in some cytokines yet remains generally low-grade, reversible, and confined to C1. Further characterization of tarlatamab’s safety is ongoing. References 1. Borghaei H, et al. OA12.05. WCLC 2022. Aug 8, 2022.
Clinical trial identification
NCT03319940.
Editorial acknowledgement
Medical writing support was provided by Eugene Gillespie, PhD of Amgen Inc.
Legal entity responsible for the study
Amgen Inc.
Funding
Amgen Inc.
Disclosure
S. Champiat: Financial Interests, Personal, Invited Speaker: Amgen, Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Genmab, Janssen, Merck, Novartis and Roche; Financial Interests, Personal, Other, Principal Investigator of Clinical Trials: AbbVie, Amgen, Cytovation, Eisai, Imcheck Therapeutics, Molecular Partners Ag, Merck, Ose Pharma, Pierre Fabre, Sanofi Aventis, Sotio A.S, Transgene; Financial Interests, Personal, Advisory Board: Alderaan Biotechnology, Amgen, AstraZeneca, Avacta, Celanese, Ellipses Pharma, Immunicom, Inc., Nanobiotix, Oncovita, Pierre Fabre, Seagen, Tatum Bioscience, Tollys SAS, UltraHuman8; Financial Interests, Personal, Other, Travel and congress: Amgen, AstraZeneca, Bristol Myers Squibb, Merck, Ose Pharma, Roche, Sotio; Financial Interests, Institutional, Other, As part of the Drug Development Department (DITEP) =Principal/sub-Investigator of Clinical Trials: AbbVie, Adaptimmune, Adlai Nortye USA Inc, Aduro Biotech, Agios Pharmaceuticals, Amgen, Astex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, BicycleTx Ltd, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Ca, Casi Pharmaceuticals, Inc, Celgene Corporation, Cellcentric, Chugai Pharmaceutical Co, Cullinan-Apollo, Curevarc, Daiichi Sankyo, Debiopharm, Eisai, Eisai Limited, Eli Lilly, Exelixis, Faron Pharmaceuticals Ltd, Forma Tharapeutics, Gamamabs, Genentech, Glaxosmithkline, H3 Biomedicine, Hoffmann La Roche Ag, Imcheck Therapeutics, Incyte Corporation, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Iteos Belgium SA, Janssen Cilag, Janssen Research Foundation, Janssen R&D Llc, Kura Oncology, Kyowa Kirin Pharm. Dev, Lilly France, Loxo Oncology, MedImmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Molecular Partners Ag, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology Nv, Oncoethix, Oncopeptides, Orion Pharma, Genomics, Ose Pharma, Pfizer, Pharma Mar, Pierre Fabre Medicament, Relay Therapeutics, Inc, Roche, Sanofi Aventis, Seattle Genetics, Sotio A.S, Syros Pharmaceuticals, Taiho Pharma, Tesaro, Transgene S.A, Turning Point Therapeutics, Xencor; Financial Interests, Institutional, Research Grant, As part of the Drug Development Department (DITEP) =Research Grants: AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Pfizer, Roche, Sanofi; Non-Financial Interests, Institutional, Product Samples, As part of the Drug Development Department (DITEP) =Non-financial support (drug supplied): AstraZeneca, BMS, Boringher Ingelheim, GSK, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. M. Boyer: Financial Interests, Personal, Invited Speaker: AstraZeneca, Merck Sharpe & Dohme; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Merck Sharpe & Dohme, Amgen, Janssen, Eli Lilly, EARLI, Immugene, Dizal; Non-Financial Interests, Personal, Leadership Role: Thoracic Oncology Group Australasia. L. 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Carlisle: Financial Interests, Institutional, Invited Speaker: AstraZeneca, Amgen, Hutchmed. H. 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M.L. Johnson: Financial Interests, Institutional, Research Grant: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array Biopharma, Artios Pharma, AstraZeneca, Atreca, Beigene, Bergenbio, BioAtla, Boehringer Ingelheim, Calithera Biosciences, Checkpoint Therapeutics, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Dynavax, Lilly, Elicio Therapeutics, EMD Serono, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Harpoon , Helsinn Healthcare SA, Hengrui Therapeutics, Hutchison MediPharma, Ideaya Biosciences, IGM Biosciences, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals , Loxo Oncology, Lycera, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, Oncomed Pharmaceuticals, Pfizer, PMV Pharmaceuticals, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals/Birdie Pharmaceuticals, Shattuck Labs, Silicon Therapeutics, StemCentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, Tmunity Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, WindMIL, Y-mAbs Therapeutics; Financial Interests, Institutional, Advisory Role: AbbVie, Amgen, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Checkpoint Therapeutics, CytomX Therapeutics, Daiichi Sankyo, EcoR1, Editas Medicine, Eisai, EMD Serono, G1 Therapeutics; Financial Interests, Institutional, Other: Genentech/Roche. 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Ju: Financial Interests, Personal, Stocks/Shares: Amgen; Financial Interests, Personal, Full or part-time Employment: Amgen. S. Mukherjee: Financial Interests, Personal, Stocks/Shares: Amgen; Financial Interests, Personal, Full or part-time Employment: Amgen. X. Chen: Financial Interests, Personal, Full or part-time Employment: Amgen. N. Hashemi Sadraei: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. H. Hummel: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Invited Speaker: Amgen, Bristol Myers Squibb, Amgen; Financial Interests, Institutional, Invited Speaker: Amgen, Amgen, Revolution Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Merck, Novartis, AstraZeneca, Drachen, Daiichi Sankyo, AvenCell Europe GmbH, Celgene; Non-Financial Interests, Personal, Principal Investigator: AIO-Studien-gGmbH, Lung Cancer Group Cologne.