508MO - Tarlatamab for patients (pts) with previously treated small cell lung cancer (SCLC): Primary analysis of the phase II DeLLphi-301 study

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% 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: 508MO

*Efficacy analysis set per intension-to-treat (ITT) analysis (Pts in safety substudy (n=34) not included as data immature).

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, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, Pharmamar, BeiGene, Daiichi Sankyo, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Institutional, Coordinating PI: Daiichi Sankyo, AstraZeneca, Novartis, Merck Sharp & Dohme corp, BMS, Janssen-cilag international NV, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, Pharmamar; Financial Interests, Personal, Coordinating PI: Amgen; Financial Interests, Personal, Other, Member: AACR, ASCO, ESMO; Financial Interests, Personal, Other, Foundation Board Member: AECC; Financial Interests, Personal, Other, President. ASEICA( Spanish Association of Cancer Research ): ASEICA; Financial Interests, Personal, Other, Foundation president: ONCOSUR; Financial Interests, Personal, Other, member: Small Lung Cancer Group. M. Ahn: Financial Interests, Personal, Advisory Board: AstraZeneca, TAKEDA, MSD, YUHAN, Amgen, ALPHA Pharmaceutical, Janssen, BMS, Roche, Daichi Sankyo, Merck, BOROnoI. 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, Personal, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Personal, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Personal, Member, Member of the Scientiffic Advisory Committee: CAC Hospital Universitari Parc Taulí. S. Handzhiev: Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim; Non-Financial Interests, Institutional, Principal Investigator: Boehringer Ingelheim, Amgen. I. Korantzis: Financial Interests, Personal, Principal Investigator: Amgen; Financial Interests, Personal, Sponsor/Funding: Amgen. H. Izumi: Financial Interests, Institutional, Local PI: Amgen Inc, Eisai, AbbVie; Financial Interests, Personal and Institutional, Local PI, Invited Speaker: Ono Pharmaceutical Company, AstraZeneca; Financial Interests, Personal, Other, Invited Speaker: Chugai Pharmaceutical Co., Merck Biopharma Co., Takeda Pharmaceutical Co.; Financial Interests, Personal, Other, Advisory board: 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 Tarruella: 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, Regeneron, Novartis, Roche, Sanofi; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, Biontech, Boehringer Ingelheim, Daiichi Sankyo, MSD, Gilead, Mirati, Pfizer, Regeneron, Sanofi, Roche; Financial Interests, Personal, Other, Member of DMSB: Daiichi Sankyo. H. Hummel: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Invited Speaker: Amgen, Bristol Myers Squibb, Boehringer Ingelheim; Financial Interests, Institutional, Coordinating PI: Amgen; Financial Interests, Institutional, Local PI: Amgen, Revolution Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Merck, Novartis, AstraZeneca, Dracen, Daiichi Sankyo, AvenCell Europe GmbH, Celgene; Financial Interests, Personal, Steering Committee Member: Amgen; Non-Financial Interests, Personal, Principal Investigator: AIO-Studien-gGmbH, Lung Cancer Group Cologne. 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, Personal, Advisory Role, Application of genotyping platforms in lung cancer: Guardant Health; Non-Financial Interests, Personal, Advisory Role, Clinical trials of IMPs in lung cancer and translational lung cancer biomarkers: AstraZeneca. 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, Personal, Other, Chair EORTC lung cancer group: EORTC; Non-Financial Interests, Personal, 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, Yma; Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis, Lilly, AbbVie, Eisai, G1 Therapeutics, Bristol Myers Squibb, illy, Amgen, AstraZeneca, PharmaMar, Boehringer Ingelheim, EMD Serono, XCovery, Bayer, Merck, Oncocyte, Takeda, Bayer, Jazz, Zentalis, Ipsen, Daichi, Janssen, BeiGene, Genentech, Exeli; Financial Interests, Personal, Other, IRC/DSMB: 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, Personal, Research Grant: Merck, AstraZeneca, Advaxis, BMS, Amgen, Takeda, Genmab, GSK. J. Sands: Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy: Arcus, Amgen, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Pharma Mar, Guardant, Sanofi, Takeda; Non-Financial Interests, Personal and Institutional, Principal Investigator: Amgen, Lilly, Merck, Genentech, Daiichi Sankyo, Pharma Mar, Phanes, Legend; Financial Interests, Personal, Advisory Role: Curadev. T. Jiang: Financial Interests, Personal, Full or part-time Employment, Employee: Amgen; Financial Interests, Personal, Stocks or ownership, Stockholder: Amgen. S. Mukherjee: Financial Interests, Personal, Full or part-time Employment, Employee: Amgen; Financial Interests, Personal, Stocks or ownership, Stockholder: Amgen. E. Anderson: Financial Interests, Personal, Full or part-time Employment, Employee: Amgen; Financial Interests, Personal, Stocks or ownership, Stockholder: Amgen. 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, Personal, Other, Founder: DAAN Biotherapeutics.