195MO - Tarlatamab in previously treated small cell lung cancer (SCLC): DeLLphi-300 phase I study long-term outcomes and intracranial activity

Background

Tarlatamab, a bispecific T cell engager (BiTE®) immunotherapy targeting delta-like ligand 3 (DLL3), showed durable antitumor activity and manageable safety in previously treated SCLC. Here we report long-term outcomes and intracranial activity from the DeLLphi-300 phase I study.

Methods

Tarlatamab was evaluated in patients (pts) with previously treated SCLC. Pts with treated, stable brain metastases were eligible. Primary endpoint was safety. Secondary endpoints included objective response rate (ORR) per mRECIST 1.1 by investigator, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). In retrospective exploratory analyses, CNS tumor sum of diameters (SOD) was assessed per mRANO-BM by BICR in pts with ≥ 1 brain lesion at baseline. This report, with data cutoff (DCO) 14.5 months (mos) beyond Paz-Ares, J Clin Oncol 2023, includes fully enrolled cohorts of pts treated with clinically relevant doses (≥ 10 mg) of tarlatamab.

Results

152 pts were treated with tarlatamab ≥ 10 mg (follow-up range 0.2–34.3 mos; median 12.1 mos). Across cohorts, ORR was 25.0% with mDOR of 11.2 mos (table). 25 pts had treatment duration ≥ 52 weeks (range 52–150), including 8 pts treated ≥ 104 weeks. mPFS and mOS were 3.5 mos and 17.5 mos, respectively, with PFS and OS estimates at 12 mos of 16.7% and 57.9%. Of 16 pts with a baseline CNS lesion ≥ 10 mm, CNS tumor SOD decreased ≥ 30% in 10 pts (62.5%). Of 8 pts who completed brain radiotherapy (RT) ≥ 50 days before tarlatamab initiation, 3 pts (37.5%) had ≥ 30% decrease in CNS tumor SOD. No new safety signals were identified.

Table: 195MO

^aDCO 2 Oct 2023 ^b1-step dosing: 1 mg (Day 1); target dose: Days 8, 15, then Q2W ^cCohorts: 30 mg eIV → 100 mg Q2W; 100 mg eIV → 100 mg Q2W ^dCohorts: 1 → 25 → 100 mg Q2W; 1 → 100 → 200 mg Q3W; 1 → 100 mg D1/D8 eIV, extended IV; NE, not estimable

Conclusions

In longer follow-up of DeLLphi-300, tarlatamab demonstrated durable responses and unprecedented survival outcomes in previously treated SCLC. While limited to analyses of treated, stable brain metastases, CNS tumor shrinkage following tarlatamab therapy and long after RT supports further study of intracranial efficacy of tarlatamab.

Clinical trial identification

NCT03319940.

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

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. S. .champiat: Financial Interests, Personal, Invited Speaker: Amgen Inc, Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Genmab, Janssen, Merck KGaA, Merck, Novartis, Roche, Servier; Non-Financial Interests, Personal, Principal Investigator: AbbVie, Amgen, Boehringer Ingelheim, Bolt Biotherapeutics, Centessa Pharmaceuticals, Cytovation, Eisai, GSK, Imcheck Therapeutics, Immunocore, Molecular Partners Ag, Merck, Ose Immunotherapeutics, Pierre Fabre, Replimune, Roche, Sanofi Aventis, Seagen, Sotio A.S, Transgene; Financial Interests, Personal, Other, Advisory Board/Consulting: Alderaan Biotechnology, Amgen, AstraZeneca, Avacta, BioNTech, Celanese, Domain Therapeutics, Ellipses Pharma, Genmab, Immunicom Inc., Mariana Oncology, Nanobiotix, Nextcure, Oncovita, Pierre Fabre, Seagen, Takeda, Tatum Bioscience, Tollys, UltraHuman8, Amgen; Financial Interests, Personal, Other, Support for meeting attendance and/or travel: AstraZeneca, Bristol Myers Squibb, MSD, Ose Immunotherapeutics, Roche, Sotio. M.E. Olmedo Garcia: Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Roche/Genentech, Eli Lilly and Company, Janssen, Novartis, Merck Sharp & Dohme, Bristol Myers Squibb; Financial Interests, Personal, Expert Testimony: AstraZeneca, Pfizer, Roche/Genentech, Eli Lilly and Company, Janssen, Novartis, Merck Sharp & Dohme, Bristol Myers Squibb; Other, Institutional, Sponsor/Funding: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role: AstraZeneca, Pfizer, Roche/Genentech, li Lilly and Company, Janssen, Novartis, Merck Sharp & Dohme, Bristol Myers Squibb. M. Boyer: Non-Financial Interests, Personal, Principal Investigator: Imugene, Eli Lilly, Amgen, Janssen, Pfizer, Daiichi Sankyo, Gilead, Mythic Therapeutics, Merck Sharpe and Dohme, AstraZeneca; Financial Interests, Personal, Advisory Role: Amgen. K. He: Other, Personal, Other, Consultant: Mirati Therapeutics, Perthera, Bristol Myers Squibb, Iovance Biotherapeutics, Lyell Immunopharma, AstraZeneca, BeiGene, ONCOC4, BioNTech, Obsidian, Amgen; Financial Interests, Institutional, Principal Investigator: Mirati Therapeutics, Bristol Myers Squibb, Iovance Biotherapeutics, Lyell Immunopharma, AstraZeneca, BeiGene, ONCOC4, AbbVie, Amgen, Genentech, MSK. N. Steeghs: Financial Interests, Institutional, Other, Consultation or attended advisory boards: Boehringer Ingelheim, Ellipses Pharma, GSK, Incyte, Luszana; Financial Interests, Institutional, Research Grant: AbbVie, Actuate Therapeutics, Amgen, Array, Ascendis Pharma, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Cantargia, CellCentric, Cogent Biosciences, Cresecendo Biologics, Cytovation, Deciphera, Dragonfly, Eli Lilly, Exelixis, Genentech, GSK, IDRx, Immunocore, Incyte, InteRNA, Janssen, Kinnate Biopharma, Kling Biotherapeutics, Lixte, Luszana, Merck, Merck Sharp & Dohme, Merus, Molecular Partners, Navire Pharma, Novartis, Numab Therapeutics, Pfizer, Relay Pharmaceuticals, Revolution Medicin, Roche, Sanofi, Seattle Genetics, Taiho, Takeda. 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. M.L. Johnson: Financial Interests, Institutional, Other, Support for this study: Amgen Inc; Financial Interests, Institutional, Principal Investigator: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAtla, Boehringer Ingeheim, Calithera Biosciences, Corvus Pharmaceuticals, Curis, Cytomx, Daiichi Sankyo, Dracen Pharmaceuticals, Dynavax, Lilly, EMD Serono, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare, Hengrui Therapeutics, Hutchison MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunocore, Incyte, Janssen, Kadmon Pharmaceuticals, Loxo Oncology, Lycera, Memorial Sloan-Kettering, Merck, Merus, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Pfizer, PMV Pharmaceuticals, Regneron Pharmaceuticals, Relay Therapeutics, Revolution Medicine, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals / Birdie Biopharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, TMUNITY Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, WindMIL, Y-mAbs Therapeutics, Black Diamond, Carisma Therapeutics, Elicio Therapeutics, EQRx, Immunitas Therapeutics, Kartos Therapeutics, Mirati Therapeutics, Palleon Pharmaceuticals, Rain Therapeutics; Financial Interests, Institutional, Other, Consulting work: AbbVie, Amgen, Astellas, AstraZeneca, Axelia oncology, Black Diamond, Calithera Biosciences, Checkpoint Therapeutics, CytomX Therapeutics, Daiichi Sankyo, EcoR1, Editas Medicine, Eisai, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Ideaya Biosciences, iTeos, Janssen, Lilly, Merck, Mirati Therapeutics, Molecular Axiom, Novartis, Oncorus, Regeneron Pharmaceuticals, Ribon Therapeutics, Sanofi-Aventis, Turning Point Therapeutics, VBL Therapeutics, Takeda Pharmaceuticals, Arrivant, Pyramid Biosciences, Revolution Medicines, SeaGen. T. Yoshida: Financial Interests, Personal, Invited Speaker: AstraZeneca, Daiichi Sankyo, Bristol Myers Squibb, MSD, Novartis, Merck, Chugai, Takeda, Pfizer; Financial Interests, Institutional, Research Grant: AstraZeneca, Amgen, Daiichi Sankyo, Bristol Myers Squibb, MSD, Novartis, Merck, Chugai; Financial Interests, Institutional, Principal Investigator: AstraZeneca, Amgen, Daiichi Sankyo, Bristol Myers Squibb, MSD, Novartis, Merck, Chugai; Financial Interests, Personal, Advisory Role: Pfizer, Amgen, Boehringer Ingelheim. H. Bouchaab: Financial Interests, Institutional, Advisory Role: Amgen Inc, AstraZeneca, Bristol Myers Squibb, Janssen, MSD, Roche, Takeda; Financial Interests, Institutional, Speaker’s Bureau: Amgen Inc., Bristol Myers Squibb, Janssen, MSD, Roche, Takeda; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Institutional, Other, Travel, Accommodations, Expenses: Amgen, AstraZeneca, Bristol Myers Squibb, MSD, Roche, Sanofi. A. Dowlati: Financial Interests, Personal, Advisory Role: AbbVie/Stemcentrx, AstraZeneca, Bristol Myers Squibb, Ipsen, Merck, Tempus; Financial Interests, Institutional, Research Grant: AbbVie/Stemcentrx, Amgen, Astellas Pharma, Bayer, Bicycle Therapeutics, Bristol Myers Squibb, Coordination Pharmaceuticals, Gilead Sciences, Ipsen, Lilly/ImClone, Mirati Therapeutics, Pionyr, Seagen, Takeda, Tesaro. H. Borghaei: Financial Interests, Institutional, Research Grant: BMS, Lilly, Amgen Inc.; Financial Interests, Personal, Advisory Board: BMS, Lilly, Genentech, Pfizer, Merck, EMD-Serono, Boehringer Ingelheim, AstraZeneca, Novartis, GenMab, Regeneron, BioNTech, Amgen Inc., Axiom, PharmaMar, Takeda, Mirati Therapeutics, Daiichi Sankyo, Guardant, Natera, Oncocyte, BeiGene, iTEO, Jazz Pharmaceuticals, Janssen, Puma Biotechnology, BerGenBio, Bayer, IO Biotech, Grid Therapeutics; Financial Interests, Personal, Other, Data and Safety Monitoring Board: University of Pennsylvania: CAR T Program, Takeda, Incyte, Novartis, SpringWorks Therapeutics; Financial Interests, Personal, Full or part-time Employment: Fox Chase Cancer Center; Financial Interests, Personal, Stocks/Shares: Sonnet BioTherapeutics, Inspirna, Inc., Nucleai; Financial Interests, Personal, Other, Honoraria: Amgen, Pfizer, Daiichi Sankyo, Regeneron; Financial Interests, Personal, Other, Support for travel: Amgen Inc., BMS, Merck, Lilly, EMD- Serono, Genentech, Regeneron, Mirati Therapeutics. E. Felip: Financial Interests, Personal, Invited Speaker: Amgen Inc, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffman-La Roche, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, Merck Sharp & Dohme, Peervoice, Pfizer, Sanofi, Takeda, Touch Oncology; Financial Interests, Personal, Advisory Board: AbbVie, Amgen Inc., AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffman-La Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Pfizer, Regeneron, Sanofi, Takeda, Turning Point, Daiichi Sankyo; Financial Interests, Personal, Member of Board of Directors, Independent Member of the Board: Grifols. P.J. Jost: Financial Interests, Personal, Invited Speaker: Bayer, Boehringer, Novartis, Pfizer, Servier, Roche, BMS, Celgene, Pierre Fabre, Janssen/Johnson&Johnson, MSD, Merck, Sanofi/Aventis, Ipsen, Amgen Inc.; Financial Interests, Personal, Expert Testimony: Bayer, Boehringer, Novartis, Pfizer, Servier, Roche, BMS, Celgene, Pierre Fabre, Janssen/Johnson&Johnson, MSD, Merck, Sanofi/Aventis, Ipsen, Amgen Inc.; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo; Financial Interests, Personal, Royalties: Venetoclax and MLKL, WEHI; Financial Interests, Institutional, Research Grant: Boehringer, Novartis, Roche, Pierre Fabre, Stemline; Financial Interests, Institutional, Funding: Boehringer, Novartis, Roche, Pierre Fabre, Stemline; Non-Financial Interests, Institutional, Principal Investigator: Boehringer, Novartis, Pierre Fabre, Stemline; Financial Interests, Personal, Advisory Role: Bayer, Boehringer, Novartis, Pfizer, Servier, Roche, BMS, Celgene, Janssen / Johnson&Johnson, MSD, Merck, Sanofi/Aventis, Ipsen, Amgen. S. Gadgeel: Financial Interests, Personal, Expert Testimony: AstraZeneca, Pfizer, Takeda, BMS, Gilead, Boehringer Ingelheim, Arcus, Blueprint, Mirati Therapeutics, Novartis, Daiichi Sankyo, AbbVie, Regeneron, Janssen, Eisai, Merck; Financial Interests, Personal, Other, Serves on Independent Data Monitoring Board: AstraZeneca; Financial Interests, Personal, Other, Travel support: Merck; Financial Interests, Personal, Other, Travel Support: Mirati Therapeutics. X. Chen: Financial Interests, Personal, Full or part-time Employment: Amgen Inc; Financial Interests, Personal, Stocks/Shares: Amgen Inc. Y. Yu: Financial Interests, Personal, Full or part-time Employment: Amgen Inc; Financial Interests, Personal, Stocks/Shares: Amgen Inc. P. Martinez: Financial Interests, Personal, Full or part-time Employment: Amgen Inc; Financial Interests, Personal, Stocks/Shares: Amgen Inc. A. Parkes: Financial Interests, Personal, Full or part-time Employment: Amgen Inc; Financial Interests, Personal, Stocks/Shares: Amgen Inc. L. Paz-Ares: Financial Interests, Personal, Leadership Role: ALTUM Sequencing, Genomica; Financial Interests, Personal, Other, Honoraria: Amgen Inc., AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Daiichi Sankyo, Janssen, Lilly, Medscape, Merck Serono, Mirati Therapeutics, MSD, Novartis, Pfizer, PharmaMar, Regeneron, Roche/Genentech, Sanofi, Takeda, GSK; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, BMS, Lilly, Merck Serono, MSD Oncology, Pfizer, Roche/Genentech; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Kura Oncology, MSD, Pfizer, PharmaMar; Other, Personal, Other: Amgen Inc., Ipsen, Merck, Novartis, Pfizer, Roche, Sanofi, Servier.