Abstract 1668TiP
Background
Delta-like ligand 3 (DLL3) is a promising therapeutic target highly expressed in SCLC and minimally expressed in normal tissues. AMG 757 is an HLE BiTE therapy that binds DLL3 on cancer cells and CD3 on T cells, resulting in redirected T cell-dependent killing of tumor cells. In phase I, AMG 757 every 2 wk was tolerable with encouraging efficacy up to 100 mg in SCLC.1,2 In early trials, programmed cell death-1 (PD-1) or ligand (PD-L1) antibodies provided efficacy in relapsed/refractory (RR) SCLC.3,4 AMG 404 is a monoclonal antibody targeting PD-1. In vitro, AMG 757 and AMG 404 increased T cell mediated lysis of tumor cells compared to AMG 757 alone (Amgen data on file); hence, the combination may increase antitumor activity.
Trial design
This multicenter, open-label, phase Ib study is evaluating AMG 757 with AMG 404. Dose exploration will estimate the phase II dose (RP2D) of AMG 757 with AMG 404, followed by dose expansion to confirm safety and tolerability. Key eligibility criteria: adults with confirmed RR SCLC whose disease progressed/recurred after ≥1 platinum-based chemotherapy regimen, ECOG performance status 0–1, measurable lesions per modified RECIST 1.1, and no untreated or symptomatic brain metastases. Prior therapy, including anti-PD-1 or PD-L1 therapy, is permitted ≥28 days before the first AMG 757 dose. Primary objectives: evaluate safety/tolerability and determine the RP2D of AMG 757 with AMG 404. Secondary objectives: evaluate preliminary antitumor activity and characterize pharmacokinetics of AMG 757 in combination. Exploratory objectives: assess immunogenicity and changes in blood and tumor biomarkers. During dose exploration, a modified toxicity probability interval design will be used for decision rules. The study (NCT04885998) is open and recruiting patients. References 1: Owonikoko T, et al. J Thorac Oncol. 2021;16:S126. 2. Owonikoko TK, et al. Abstract 8510. Presented at: ASCO Annual Meeting, June 4e8, 2021; Virtual. 3. Chung HC, et al. J Thorac Oncol. 2020;15(4):618-627. 4. Ready N, et al. J Thorac Oncol. 2019;14(2):237-244.
Clinical trial identification
EudraCT 2020-005957-26; NCT04885998.
Editorial acknowledgement
Editorial support was provided by Erin P. O’Keefe, PhD, and Lee Hohaia, PharmD, CMPP (ICON, North Wales, PA, USA).
Legal entity responsible for the study
Amgen Inc.
Funding
Amgen Inc.
Disclosure
A. Dowlati: Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Speaker’s Bureau: Loxo; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Speaker’s Bureau: Incuron; Financial Interests, Personal, Speaker’s Bureau: Takeda; Financial Interests, Personal, Speaker’s Bureau: Regeneron; Financial Interests, Personal, Speaker’s Bureau: Tesaro; Financial Interests, Personal, Speaker’s Bureau: Seattle Genetics; Financial Interests, Personal, Speaker’s Bureau: Symphogen; Financial Interests, Personal, Speaker’s Bureau: AbbVie; Financial Interests, Personal, Speaker’s Bureau: Ipsen. L.A. Byers: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: GenMab; Financial Interests, Personal, Advisory Role: Sierra Oncology; Financial Interests, Personal, Advisory Role: PharmaMar; Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Alethia; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Jazz Pharmaceuticals; Financial Interests, Personal, Advisory Role: Genentech; Financial Interests, Personal, Advisory Role: Debiopharm Group; Financial Interests, Research Grant: AstraZeneca; Financial Interests, Research Grant: GenMab; Financial Interests, Research Grant: Sierra Oncology; Financial Interests, Research Grant: Tolero Pharmaceuticals; Financial Interests, Institutional, Advisory Board, Chair of MDACC-Amgen Alliance: Amgen. M.L. Johnson: Financial Interests, Personal, Advisory Role: Otsuka; Financial Interests, Personal, Advisory Role: Genentech/Roche; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Calithera Biosciences; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Loxo; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Mirati Therapeutics; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Mersana; Financial Interests, Personal, Advisory Role: BeiGene; Financial Interests, Personal, Advisory Role: Incyte; Financial Interests, Personal, Advisory Role: Guardant Health; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Ribon Therapeutics; Financial Interests, Personal, Advisory Role: Achilles Therapeutics; Financial Interests, Personal, Advisory Role: Atreca; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: Gristone Oncology; Financial Interests, Personal, Advisory Role: Janssen Oncology; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Association of Community Cancer Centers (ACCC); Financial Interests, Personal, Other, Travel, accommodations, expenses: AbbVie; Financial Interests, Personal, Other, Travel, accommodations, expenses: Astellas Pharma; Financial Interests, Personal, Other, Travel, accommodations, expenses: AstraZeneca; Financial Interests, Personal, Other, Travel, accommodations, expenses: Boehringer Ingelheim; Financial Interests, Personal, Other, Travel, accommodations, expenses: Clovis Oncology; Financial Interests, Personal, Other, Travel, accommodations, expenses: Daiichi Sankyo; Financial Interests, Personal, Other, Travel, accommodations, expenses: EMD Serono; Financial Interests, Personal, Other, Travel, accommodations, expenses: BMS; Financial Interests, Personal, Other, Travel, accommodations, expenses: Exelixis; Financial Interests, Personal, Other, Travel, accommodations, expenses: Genentech; Financial Interests, Personal, Other, Travel, accommodations, expenses: Incyte; Financial Interests, Personal, Other, Travel, accommodations, expenses: Merck; Financial Interests, Personal, Other, Travel, accommodations, expenses: Pfizer; Financial Interests, Personal, Other, Travel, accommodations, expenses: Sysmex; Financial Interests, Personal, Other, Travel, accommodations, expenses: Vapotherm; Financial Interests, Personal, Other, Travel, accommodations, expenses: Janssen Oncology; Financial Interests, Personal, Other, Travel, accommodations, expenses: Lilly; Financial Interests, Personal, Other, Travel, accommodations, expenses: Novartis; Financial Interests, Personal, Other, Travel, accommodations, expenses: Sanofi; Financial Interests, Research Grant: EMD Serono; Financial Interests, Research Grant: Kadmon; Financial Interests, Research Grant: Janssen; Financial Interests, Research Grant: Mirati Therapeutics; Financial Interests, Research Grant: Genmab; Financial Interests, Research Grant: Pfizer; Financial Interests, Research Grant: AstraZeneca; Financial Interests, Research Grant: Stem CentRx; Financial Interests, Research Grant: Novartis; Financial Interests, Research Grant: Checkpoint Therapeutics; Financial Interests, Research Grant: Array BioPharma; Financial Interests, Research Grant: Regeneron; Financial Interests, Research Grant: Merck; Financial Interests, Research Grant: Hengrui Pharmaceutical; Financial Interests, Research Grant: Lycera; Financial Interests, Research Grant: BeiGene; Financial Interests, Research Grant: Tarveda Therapeutics; Financial Interests, Research Grant: Loxo; Financial Interests, Research Grant: AbbVie; Financial Interests, Research Grant: Boehringer Ingelheim; Financial Interests, Research Grant: Guardant Health; Financial Interests, Research Grant: Daiichi Sankyo; Financial Interests, Research Grant: Sanofi; Financial Interests, Research Grant: CytomX Therapeutics; Financial Interests, Research Grant: Dynavax; Financial Interests, Research Grant: Birdie; Financial Interests, Research Grant: Corvus Pharmaceuticals; Financial Interests, Research Grant: Incyte; Financial Interests, Research Grant: Genocea Biosciences; Financial Interests, Research Grant: Gritstone Oncology; Financial Interests, Research Grant: Amgen; Financial Interests, Research Grant: Genentech/Roche; Financial Interests, Research Grant: Adaptimmune; Financial Interests, Research Grant: Syndax; Financial Interests, Research Grant: Neovia Oncology; Financial Interests, Research Grant: Acerta Pharma; Financial Interests, Research Grant: Takeda; Financial Interests, Research Grant: Shattuck Labs; Financial Interests, Research Grant: GlaxoSmithKline; Financial Interests, Research Grant: Apexigen; Financial Interests, Research Grant: Atreca; Financial Interests, Research Grant: OncoMed; Financial Interests, Research Grant: Lilly; Financial Interests, Research Grant: Immunocore; Financial Interests, Research Grant: Jounce Therapeutics; Financial Interests, Research Grant: University of Michigan; Financial Interests, Research Grant: WindMIL; Financial Interests, Research Grant: TCR2 Therapeutics; Financial Interests, Research Grant: Arcus Biosciences; Financial Interests, Research Grant: Ribon Therapeutics. R. Aljumaily: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Regeneron. H. Prenen: Financial Interests, Personal, Other, Honoraria and/or travel grants: Bayer; Financial Interests, Personal, Other, Honoraria and/or travel grants: Roche; Financial Interests, Personal, Other, Honoraria and/or travel grants: Amgen; Financial Interests, Personal, Other, Honoraria and/or travel grants: Ipsen; Financial Interests, Personal, Other, Honoraria and/or travel grants: Merck; Financial Interests, Personal, Other, Honoraria and/or travel grants: Novartis; Financial Interests, Personal, Other, Honoraria and/or travel grants: Sanofi. A. Zhang: Financial Interests, Personal, Full or part-time Employment: Amgen Inc.; Financial Interests, Personal, Stocks/Shares: Amgen Inc. M. Minocha: Financial Interests, Personal, Full or part-time Employment: Amgen Inc.; Financial Interests, Personal, Stocks/Shares: Amgen Inc. A. Shetty: Financial Interests, Personal, Full or part-time Employment: Amgen Inc.; Financial Interests, Personal, Stocks/Shares: Amgen Inc. N. Hashemi Sadraei: Financial Interests, Personal, Full or part-time Employment: Amgen Inc.; Financial Interests, Personal, Stocks/Shares: Amgen Inc.