Abstract 214TiP
Background
SCLC is an aggressive disease with poor survival. Despite initial response to chemoradiation, most patients with LS-SCLC relapse. Between 85-96% of patients with SCLC have tumor expression of Delta-like ligand 3 (DLL3), a Notch ligand aberrantly expressed on the surface of SCLC cells with minimal expression in healthy cells, making DLL3 an attractive therapeutic target. In the phase II DeLLphi-301 study, tarlatamab, a bispecific T cell engager (BiTE®) immunotherapy targeting DLL3 and T cell co-receptor CD3, demonstrated antitumor activity and a manageable safety profile in patients with previously treated extensive stage-SCLC: 40% objective response and a 6-month overall survival (OS) rate (KM estimate) of 73% at 10 mg Q2W (NEJM 2023;389:2063).
Trial design
DeLLphi-306 is a randomized (1:1), double-blind, placebo-controlled Phase 3 trial examining tarlatamab (10 mg Q2W in 28-day cycles) clinical activity and safety in ≈ 400 patients with LS-SCLC following concurrent chemoradiation. Key patient inclusion criteria include age ≥ 18 years, histologically/cytologically confirmed LS-SCLC, completion of platinum-based chemotherapy with concurrent radiotherapy without progression, ECOG PS ≤ 1, chemoradiotherapy-attributed toxicities resolved to grade ≤ 1 excluding alopecia, and life expectancy ≥ 12 weeks. Key exclusion criteria include transformed NSCLC; interstitial lung disease; active pneumonitis; non-concurrent chemotherapy and thoracic radiotherapy during chemoradiation; prior DLL3 pathway-selective inhibitor therapy; and history of severe/life-threatening events from immune-mediated therapy. Primary endpoint is progression-free survival (PFS) per blinded independent central review (RECIST 1.1) with OS as a key secondary endpoint. Additional secondary endpoints include investigator-assessed PFS, objective response, disease control, duration of response, time to progression, pharmacokinetics, tarlatamab immunogenicity, and safety/tolerability.
Clinical trial identification
NCT06117774.
Editorial acknowledgement
Medical writing support was provided by William W Stark, Jr, PhD, Amgen Inc.
Legal entity responsible for the study
Amgen.
Funding
Amgen.
Disclosure
H. Hummel: Financial Interests, Personal, Invited Speaker: Amgen Inc, Bristol Myers Squibb, Boehringer Ingelheim; Financial Interests, Personal, Other, Consultancy (including expert testimony): Amgen Inc, Boehringer Ingelheim; Financial Interests, Institutional, Principal Investigator: Amgen Inc, Boehringer Ingelheim, Bristol Myers Squibb, AstraZeneca, Celgene, Merck, Novartis, Revolution Medicines, Daiichi Sankyo, Dracen; Financial Interests, Personal, Advisory Role: Amgen Inc, Boehringer Ingelheim, Bristol Myers Squibb, Roche. L. Paz-Ares: Financial Interests, Personal, Leadership Role: ALTUM Sequencing, Genomica; Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Daiichi Sankyo, GSK, Janssen, Lilly, Medscape, Merck Serono, Mirati Therapeutics, MSD, Novartis, Pfizer, PharmaMar, Regeneron, Roche/Genentech, Sanofi, Takeda; Financial Interests, Personal, Other: AstraZeneca, Amgen, Ipsen, Merck, Novartis, Pfizer, Roche, Sanofi, Servier; Financial Interests, Personal, Speaker’s Bureau: BMS, Lilly, Merck Serono, MSD Oncology, Pfizer, Roche/Genentech; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Kura Oncology, MSD, Pfizer, PharmaMar. F. Blackhall: Financial Interests, Personal, Other, Scientific Advisory Board: AbbVie, Amgen Inc., Boehringer Ingelheim. A.C. Chiang: Financial Interests, Personal, Other, Consultant: AstraZeneca; Financial Interests, Personal, Other, Advisory Board: AstraZeneca, Daiichi Sankyo, Janssen; Financial Interests, Institutional, Leadership Role: SWOG executive Officer; Financial Interests, Institutional, Principal Investigator: BMS, AbbVie, Amgen Inc., GNE, AstraZeneca. A. Dowlati: Financial Interests, Personal, Advisory Role: Ipsen, AstraZeneca, Amgen. J.W. Goldman: Financial Interests, Personal, Invited Speaker: AstraZeneca, AbbVie; Financial Interests, Personal, Other, Consultancy (including expert testimony): AbbVie; Financial Interests, Institutional, Research Grant: AstraZeneca, AbbVie, BMS, Genentech, Amgen Inc.; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Personal, Advisory Role: Amgen, Daiichi Sankyo. H. Izumi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly, Takeda, MSD; Financial Interests, Institutional, Principal Investigator: Amgen, AstraZeneca, AbbVie, Takeda, Ono, Bristol Myers Squibb, Eisai; Financial Interests, Personal, Advisory Role: Amgen. T.S.K. Mok: Financial Interests, Personal, Invited Speaker: ACEA Pharma, Alpha Biopharma Co. Ltd, Amgen Inc., Amoy Diagnostics Co. Ltd, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Daz Group, Fishawack Facilitate Ltd, InMed Medical Communication, Janssen Pharmaceutica NV, Jiahui Holdings Co. Ltd, LiangYiHui Healthcare, Lilly, Lucence Health Inc, MD Health Brazil, Medscape LLC, Merck Pharmaceutical HK Ltd, Merck Sharp & Dohme, MIRXES, Novartis, OrigiMed Co. Ltd, P. Permanyer SL, PeerVoice, Physicians'Education Resource (PER), Pfizer, PrIME Oncology, Research to Practice, Roche Pharmaceuticals/Diagnostics/Foundation One, Sanofi-Aventis, Shanghai BeBirds Translation & Consulting Co., Ltd, Shanghai Promedican Pharmaceuticals Co., Ltd, Taiho Pharmaceutical Co. LTd, Takeda Oncology, Touch Independent Medical Education Ltd.; Financial Interests, Personal, Other, Consultancy (including expert testimony): AbbVie Inc, ACEA Pharma, Adagene, Alpha Biopharma Co., Ltd, Amgen Inc., Amoy Diagnostics Co. Ltd, AnHeart Therapeutics, AstraZeneca, Aveo Pharmaceuticals, Inc., Bayer Healthcare Pharmaceuticals Ltd., BeiGene, BerGenBio ASA, Berry Oncology, Boehringer Ingelheim, Blueprint Medicines Corporation, BMS, Bowtie Life Insurance Company Limited, Bridge Biotherapeutics Inc, Covidien LP, C4 Therapeutics Inc., Cirina Ltd, CStone Pharmaceuticals, Curio Science, D3 Bio Ltd, Da Volterra, Daiichi Sankyo, Eisai, Elevation Oncology, F. Hofffman-La Roche Ltd, Genentech, GLG's Healthcare, Fishawack Facilitate Ltd, G1 Therapeutics Inc., geneDecode Co., Ltd, Gilead Sciences, Inc., Gritstone Oncology, Inc., Guardant Health, Hengrui Therapeutics Inc, Hutch Med, Ignyta, Inc., Illumina, Inc., Incyte Corporation, Iniviata, IQVIA, Janssen, Lakeshore Biotech Ltd, Lilly, Lunit USA, Inc., Loxo Oncology, Lucence Health Inc, Medscape LLC/WebMD, Medtronic, Merck Serono, MSD, Mirati Therapeutics Inc., MiRXES, MoreHealth, Novartis, Novocure GmbH, Omega Therapeutics Inc, OrigiMed, OSE Immuotherapeutics, PeerVoice, Pfizer, PriME Oncology, Prenetics, Puma Biotechnology Inc, Roche Pharmaceuticals/Diagnostics/Foundation Once, Sanofi-Aventis, SFJ Pharmaceutical Ltd, Simcere of America Inc, Summit Therapeutics Sub, Inc, Synergy Research, Takeda Pharmaceuticals HK Ltd, Tigermed, Vertex Pharmaceuticals, Virtus Medical Group, XENCOR, Inc, Yuhan Corporation; Financial Interests, Personal, Invited Speaker, Consultancy (including expert testimony): Qiming Development (HK) Ltd, Regeneron Pharmaceuticals Inc; Financial Interests, Personal, Officer: AstraZeneca PLC, HutchMEd, Aurora; Financial Interests, Personal, Member of Board of Directors: AstraZeneca PLC, HutchMEd, Aurora; Financial Interests, Personal, Stocks/Shares: Alentis Therapeutics AG, AstraZeneca, Aurora Tele-Oncology Ltd, Biolidics Ltd, HutchMEd, Prenetics, D3 Bio, Lunit Inc; Financial Interests, Institutional, Research Grant: straZeneca, BMS, G1 Therapeutics, MSD, Merck Serono, Novartis, Pfizer, Roche, SFJ, Takeda, XCovery; Financial Interests, Personal, Sponsor/Funding: AstraZeneca, MiRXES, Daiichi Sankyo, Novartis, Roche, AbbVie, Pfizer, Liangyihui, Zai Lab; Financial Interests, Personal, Advisory Role: AbbVie Inc, ACEA Pharma, Amgen, AstraZeneca, Berry Oncology, Blueprint Medicines Corporation, Boehringer Ingelheim, Bowtie Life Insurance Co Ltd, Bristol Myers Squibb, C4 Therapeutics Inc, Covidien LP, CStone Pharmaceuticals, Curio Science, D3 Bio Ltd. J. Sands: Financial Interests, Personal, Other, Consultancy (including expert testimony): AstraZeneca, Amgen Inc., AbbVie, Boehringer Ingelheim, Daiichi Sankyo, G1 Therapeutics, Medtronic, PharmaMar; Financial Interests, Personal and Institutional, Research Grant: Amgen, Harpoon; Financial Interests, Institutional, Principal Investigator: Amgen, Daiichi Sankyo, PharmaMar, Genentech, Merck, Phanes, Legend, Loxo, Shenzhen, Chipscreen Biosciences; Financial Interests, Personal, Advisory Role: Curadev. P. Martinez, E. Anderson, P. Bharania, B. Yu, Y. Yu: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. M. Provencio Pulla: Financial Interests, Personal and Institutional, Invited Speaker: Bristol Myers Squibb, Roche, MSD, AstraZeneca, Takeda, Eli Lilly, F. Hoffman La Roche, Janssen, Pfizer; Financial Interests, Personal and Institutional, Other, Consulting fees: Bristol Myers Squibb, Roche, MSD, AstraZeneca, Takeda, Eli Lilly, F Hoffman-La Roche, Janssen, Pfizer, Takeda; Financial Interests, Personal and Institutional, Research Grant: MSD, AstraZeneca, Roche, Boehringer Ingelheim, Takeda; Financial Interests, Personal and Institutional, Other, Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Bristol Myers Squibb, Roche, MSD, AstraZeneca, Takeda, Eli Lilly, F Hoffman-La Roche, Janssen, Pfizer; Financial Interests, Personal and Institutional, Other, Support for attending meetings and/or travel: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F Hoffman-La Roche, Pierre Fabre Pharmaceuticals, Takeda.