Abstract LBA92
Background
Tarlatamab, a bispecific T-cell engager (BiTE), represents a new immunotherapeutic approach for SCLC. It binds to both delta-like ligand 3 (DLL3) on SCLC cells and CD3 on T cells, resulting in T-cell mediated tumor lysis. A phase 1 study demonstrated encouraging safety and efficacy (median duration of response (mDoR): 12.3 mo; median overall survival (mOS): 13.2 mo) in previously treated SCLC. Here, the phase 2 data from the DeLLphi-301 study are presented.
Methods
Pts with SCLC who relapsed after 1 platinum-based regimen (± checkpoint inhibitor) and at least 1 other prior line of therapy received 10 mg or 100 mg tarlatamab Q2W. The primary endpoint was objective response rate (ORR) by blinded independent central review (RECIST 1.1). Other endpoints were DoR, progression-free survival (PFS), OS, and treatment-emergent adverse events (TEAEs).
Results
Overall, 220 pts received tarlatamab. The median follow-up was 10.6 mo for efficacy outcomes (Table). At the 10 mg dose, ORR was 40.0%, mPFS was 4.9 mo, mOS was 14.3 mo, and mDoR was not reached, with 57.5% of responders experiencing ≥ 6 mo of response and 55.0% still with an ongoing response. The most common TEAE was cytokine release syndrome (CRS; 51.1%, 10 mg; 60.9%, 100 mg), primarily occurring in cycle 1, and was mostly grade 1 or 2. Incidence of grade 3 CRS (0.8%, 10 mg; 5.7%, 100 mg) and grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS) and associated neurologic events was low (0%, 10 mg; 4.6%, 100 mg), with no grade 4 or 5 events. Discontinuations due to treatment-related AEs were infrequent (3.0%, 10 mg; 3.4%, 100 mg). Similar safety profiles were seen with 24h or 48h inpatient monitoring. Table: LBA92
10 mg (n = 100)* | 100 mg (n = 88)* | |
ORR, % (97.5% CI) | 40.0 (29.1–51.7) | 31.8 (21.1–44.1) |
Complete response, n (%) | 1 (1.0) | 7 (8.0) |
Partial response, n (%) | 39 (39.0) | 21 (23.9) |
Stable disease, n (%) | 30 (30.0) | 27 (30.7) |
Progressive disease, n (%) | 20 (20.0) | 13 (14.8) |
Not evaluable, n (%) | 2 (2.0) | 4 (4.5) |
Death before post-baseline scan, n (%) | 6 (6.0) | 13 (14.8) |
No post-baseline scan, n (%) | 2 (2.0) | 3 (3.4) |
mDoR, mo (95% CI) | NE (5.9–NE) | NE (6.6–NE) |
Disease control rate % (95% CI) | 70.0 (60.0, 78.8) | 62.5 (51.5, 72.6) |
mOS, mo (95% CI) | 14.3 (10.8–NE) | NE (12.4–NE) |
mPFS, mo (95% CI) | 4.9 (2.9–6.7) | 3.9 (2.6–4.4) |
*Efficacy analysis set per intention-to-treat (ITT) analysis (Pts in safety substudy (n = 34) not included as data immature). NE = not estimable
Conclusions
Tarlatamab demonstrated impressive antitumor activity with durable responses and promising survival. Tarlatamab showed a favorable benefit-risk profile with no new safety signals, supporting the use of tarlatamab in pts with previously treated SCLC.
Clinical trial identification
NCT05060016.
Editorial acknowledgement
Medical writing support for the development of this abstract was provided by Liz Leight, PhD, an employee of Amgen Inc. and Sukanya Raghuraman, PhD, of Cactus Life Sciences, part of Cactus Communications, and was funded by Amgen Inc.
Legal entity responsible for the study
Amgen Inc.
Funding
Amgen Inc.
Disclosure
L. Paz-Ares: Financial Interests, Personal, Invited Speaker: MSD, Lilly, Janssen Pharmaceuticals, Mirati Therapeutics, Bristol Myers Squibb, AstraZeneca, PharmaMar, GSK, Sanofi; Financial Interests, Personal, Member of Board of Directors: STAb Therapeutics, Altum sequencing; Non-Financial Interests, Personal, Member: IASLC, ESMO, SEOM, ASEICA, CNIO, ONCOSUR, AECC, CRIS; Financial Interests, Personal, Advisory Role: Lilly, MSD, Roche, PharmaMar, Merck, AstraZeneca, Novartis, Servier, Amgen, Pfizer, Sanofi, Bayer, Bristol Myers Squibb, Mirati Therapeutics, GSK, Janssen, Takeda, Daiichi Sankyo. M. Ahn: Financial Interests, Personal, Invited Speaker: AstraZeneca, Yuhan, Takeda, Amgen, MSD, Merck, Daiichi Sankyo; Financial Interests, Personal, Other, Consultancy (including expert testimony): AstraZeneca, Yuhan, Arcus, Takeda, Amgen, MSD, Merck, Daiichi Sankyo, Alpha Pharmaceuticals, Pfizer, Voronoi, Eutilex; Financial Interests, Personal, Advisory Role: AstraZeneca, Yuhan, Arcus, Takeda, Amgen, MSD, Merck, Daiichi Sankyo, Alpha Pharmaceuticals, Pfizer, Voronoi, Eutilex. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, Sanofi, Takeda, Touch Oncology, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Local PI, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, BeiGene, Boehringer Ingelheim GmbH, Bristol-Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Non-Financial Interests, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Member, Member of the Scientific Advisory Committee: CAC Hospital Universitari Parc Taulí. S. Handzhiev: Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Non-Financial Interests, Institutional, Principal Investigator: Boehringer Ingelheim, Amgen. I. Korantzis: Financial Interests, Personal, Principal Investigator: Amgen Inc.; Financial Interests, Personal, Sponsor/Funding: Amgen Inc.. H. Izumi: Financial Interests, Personal, Invited Speaker: Takeda, Merck, Ono Pharmaceutical, MSD, Chugai, Bristol Myers Squibb, Japan; Financial Interests, Institutional, Principal Investigator: AbbVie, AstraZeneca, Amgen, Takeda, Eisai, Ono Pharmaceutical; Financial Interests, Personal, Advisory Role: Amgen. K. Ohashi: Financial Interests, Personal, Invited Speaker: Eli Lilly Japan, Kyowa-Kirin, Chugai Pharmaceutical Co., Ltd., Novartis Japan; Financial Interests, Institutional, Local PI: BeiGene, Daiichi-Sakyo, Amgen, Eli Lilly; Financial Interests, Personal, Research Grant: Daiichi Sankyo, Eli Lilly Japan, Chugai Pharmaceutical Co., Ltd.. M. Majem: Financial Interests, Personal, Advisory Board: Amgen, Roche, AstraZeneca, Takeda, Janssen, Cassen Recordati, BMS; Financial Interests, Personal, Invited Speaker: Amgen, Roche, AstraZeneca, Pfizer, Takeda, Helsinn; Financial Interests, Institutional, Funding: BMS, AstraZeneca, Roche. J. Wolf: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Blueprint, BMS, Boehringer-Ingelheim, Daiichi Sankyo, Ignyta, Janssen, Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda; Financial Interests, Personal, Invited Speaker: Bayer, Chugai; Financial Interests, Institutional, Research Grant: BMS, Janssen, Novartis, Pfizer. M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, BMS, Boehringer-Ingelheim, Lilly, MSD, Merck, Novartis, Regeneron, Roche, Sanofi; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, Biontech, Boehringer-Ingelheim, Daiichi Sankyo, Gilead, MSD, Mirati, Pfizer, Regeneron, Sanofi, Roche; Financial Interests, Personal, Other, Member of DMSB: Daiichi Sankyo. H. Hummel: Non-Financial Interests, Institutional, Principal Investigator: Amgen Inc., Revolution Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Merck, Novartis, AstraZeneca, Dracen Pharmaceutical, Daiichi Sankyo, AvenCell, Celgene; Financial Interests, Institutional, Sponsor/Funding: Amgen Inc., Boehringer Ingelheim, Bristol Myers Squibb, Johnson & Johnson, Revolution Medicines, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Amgen Inc., Boehringer Ingelheim, Bristol Myers Squibb, Johnson & Johnson; Financial Interests, Personal, Steering Committee Member: Amgen Inc.. F. Blackhall: Financial Interests, Personal, Invited Speaker, Educational Symposium lecture: AstraZeneca; Financial Interests, Personal, Advisory Board, NTRK Advisory Board and guidelines for diagnosis: Bayer; Financial Interests, Personal, Other, IDMC Chair: AstraZeneca; Financial Interests, Personal, Advisory Board, Small cell Advisory Board Oct 2020: Amgen; Financial Interests, Personal, Invited Speaker, ESMO Satellite Symposium November 2020: Takeda; Financial Interests, Personal, Other, Consultancy for RETinhibitor development: Blueprint; Financial Interests, Personal, Other, Real world evidence research study design and analysis (EGFR): Janssen; Financial Interests, Institutional, Coordinating PI, Institutional payment for clinical trial activities: Amgen, Pfizer; Financial Interests, Institutional, Coordinating PI, Payment for clinical trial activities: Mirati; Financial Interests, Institutional, Coordinating PI, Clinical trial activities: BMS; Financial Interests, Institutional, Funding, Real world evidence research programme: Roche; Non-Financial Interests, Advisory Role, Application of genotyping platforms in lung cancer: Guardant Health; Non-Financial Interests, Advisory Role, Clinical trials of IMPs in lung cancer and translational lung cancer biomarkers: Astra-Zeneca. A.C. Dingemans: Financial Interests, Institutional, Advisory Board: Roche, Sanofi, Amgen, Bayer, Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker: Takeda, Lilly, Jansen, Pfizer, AstraZeneca; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Local PI: Lilly, Amgen, Daiichi, JNJ, Mirati; Financial Interests, Institutional, Coordinating PI: Roche; Financial Interests, Institutional, Steering Committee Member: Roche; Non-Financial Interests, Other, Chair EORTC lung cancer group: EORTC; Non-Financial Interests, Member: IASCL, ASCO, AACR. T.K. Owonikoko: Financial Interests, Institutional, Research Funding: Novartis, Bayer, Regeneron, AstraZeneca, G1 Therapeutics, Bristol-Myers, United Therapeutics, Amgen, Loxo/Lilly, Fujifilm, Pfizer, Aeglea Biotherapeutics, Incyte, Merck, Mersana, Turning Point, Oncorus, Ipsen, Eisai, Roche/Genentech, Cardiff Oncology, Ymabs; Financial Interests, Personal, Advisory Board, Consulting/Advisory Board: Novartis, Lilly, AbbVie, Eisai, G1 Therapeutics, Bristol Myers Squibb, Amgen, AstraZeneca, PharmaMar, Boehringer Ingelheim, EMD Serono, XCovery, Bayer, Merck, Oncocyte, Takeda, Jazz, Zentalis, Ipsen, Daiichi Sankyo, Janssen, BeiGene, Genentech, Exelixis, Coherus, GenCART, Heat Biologics, Meryx; Financial Interests, Personal, Other, Independent Review Committees/Data and Safety Monitoring Board: EMD Serono, Roche/Genentech, Takeda; Financial Interests, Personal, Stocks or ownership: Cambium Oncology, Taobob LLC, Coherus Biosciences, GenCART. S.S. Ramalingam: Financial Interests, Personal, Other, Editor in Chief, CANCER journal: American Cancer Society; Financial Interests, Research Grant: Merck, AstraZeneca, Advaxis, BMS, Amgen, Takeda, Genmab, GSK. J. Sands: Financial Interests, Personal, Speaker, Consultant, Advisor: Arcus, Amgen Inc., AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, PharmaMar, Guardant Health, Sanofi, Takeda; Non-Financial Interests, Personal and Institutional, Principal Investigator: Amgen Inc., Lilly, Merck, Genentech, Daiichi Sankyo, PharmaMar, Phanes Therapeutics, Inc, Legend Biotech; Financial Interests, Personal, Advisory Role: Curadev Pharma. T. Jiang, S. Mukherjee, E. Anderson: Financial Interests, Personal, Full or part-time Employment: Amgen Inc.; Financial Interests, Personal, Stocks/Shares: Amgen Inc.. B.C. Cho: Financial Interests, Personal, Other, Consulting role: Abion, BeiGene, Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Janssen; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc; Financial Interests, Personal, Other, Advisory role: Medpacto, Blueprint medicines, RandBio, Hanmi; Financial Interests, Personal, Member of Board of Directors: Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Royalties: Champions Oncology, Crown Bioscience, Imagen; Financial Interests, Institutional, Research Grant: MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine., Janssen, Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, Therapex, JINTSbio, Hanmi, CHA Bundang Medical Center; Other, Founder: DAAN Biotherapeutics.
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