Abstract 155TiP
Background
SCLC is an aggressive cancer with a high response rate to platinum-based first-line chemotherapy. Disease recurrence is common in limited-stage and inevitable in extensive-stage becoming progressively resistant to subsequent therapies. There is no approved third-line therapy. The Notch ligand, delta-like ligand 3 (DLL3), is a promising target because it is highly expressed on the cell membrane in SCLC and minimally so in normal tissue. Tarlatamab is a DLL3-targeting HLE BiTE® immuno-oncology therapy designed to bind DLL3 on target cancer cells and CD3 on T cells, forming a cytolytic synapse and resulting in T cell activation/expansion and T cell-dependent killing of tumor cells. Interim results of an ongoing first-in-human study in patients with relapsed/refractory SCLC (NCT03319940) show preliminary evidence for tarlatamab efficacy in pretreated patients (objective response rate [ORR]: 20%) with an acceptable safety profile. These findings support further study of tarlatamab in SCLC in this area of unmet clinical need.
Trial design
NCT05060016 is a phase 2, open-label study evaluating tarlatamab in patients with relapsed/refractory SCLC after two or more lines of prior treatment. Part 1 is a dose characterization phase in which subjects will be randomized 1:1 to two active doses of tarlatamab. Part 2 will continue enrollment for the selected target dose only based on interim analysis of Part 1. Key eligibility criteria include adults with histologically or cytologically confirmed SCLC whose disease progressed/recurred following 1 platinum-based regimen (including a PD-L1 inhibitor, if standard of care, with certain exceptions per protocol) and at least 1 other line of therapy, treated brain metastases, and ECOG performance status ≤1. The primary endpoint for the primary analysis is ORR per RECIST 1.1 as assessed by blinded independent central review (BICR). Secondary objectives are to evaluate antitumor activity by additional measures (duration of response, progression-free survival, disease control rate and duration, overall survival), safety and tolerability, immunogenicity, and pharmacokinetics. Enrollment has begun.
Clinical trial identification
NCT05060016.
Editorial acknowledgement
Medical writing support for this poster was provided by Eugene Gillespie, PhD, of Amgen, Inc.
Legal entity responsible for the study
Amgen Inc.
Funding
Amgen Inc.
Disclosure
S.S. Ramalingam: Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: Genmab; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Advaxis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Genmab. M. Ahn: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: ONO; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: YUHAN; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: ONO; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Yuhan; Financial Interests, Personal, Advisory Role: Arcus; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Daichi-Sankyo; Financial Interests, Personal, Advisory Role: Alpha pharmaceutical. H. Akamatsu: Financial Interests, Personal, Invited Speaker: AstraZeneca K.K.; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim Japan Inc.; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: Eli Lilly Japan K.K.; Financial Interests, Personal, Invited Speaker: MSD K.K.; Financial Interests, Personal, Invited Speaker: Novartis Pharma K.K.; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical Co., Ltd.; Financial Interests, Personal, Research Grant: Amgen; Financial Interests, Personal, Research Grant: Chugai Pharmaceutical Co., Ltd.; Financial Interests, Personal, Research Grant: MSD K.K. F. Blackhall: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: AbbVie. H. Borghaei: Financial Interests, Personal, Research Grant: Millenium; Financial Interests, Personal, Research Grant: Merck/Celgene; Financial Interests, Personal, Research Grant: Bristol Myers Squibb/Lilly; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Genentech; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: EMD-Serono; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Genmab; Financial Interests, Personal, Advisory Role: Regeneron; Financial Interests, Personal, Advisory Role: BioNTech; Financial Interests, Personal, Advisory Role: Cantargia AB; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Advisory Role: Axiom; Financial Interests, Personal, Advisory Role: PharmaMar; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: Huya Bio; Financial Interests, Personal, Advisory Role: Mirati; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Guardant; Financial Interests, Personal, Advisory Role: Natera; Financial Interests, Personal, Advisory Role: Oncocyte; Financial Interests, Personal, Stocks/Shares, Scientific advisory board: Sonnetbio; Financial Interests, Personal, Stocks/Shares, Scientific advisory board: Rgenix; Financial Interests, Personal, Stocks/Shares, Scientific advisory board: Nucleai; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo. H. Hummel: Financial Interests, Personal, Invited Speaker: Johnson & Johnson; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: Johnson & Johnson; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Amgen. M. Johnson: Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Institutional, Research Grant: Acerta; Financial Interests, Institutional, Research Grant: Adaptimmune; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Apexigen; Financial Interests, Institutional, Research Grant: Arcus Biosciences; Financial Interests, Institutional, Research Grant: Array Biopharma; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Atreca; Financial Interests, Institutional, Research Grant: Beigene; Financial Interests, Institutional, Research Grant: BerGenBio; Financial Interests, Institutional, Research Grant: BioAtla; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Calithera Biosciences; Financial Interests, Institutional, Research Grant: Checkpoint Therapeutics; Financial Interests, Institutional, Research Grant: Corvus Pharmaceuticals; Financial Interests, Institutional, Research Grant: Curis; Financial Interests, Institutional, Research Grant: CytomX; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Dracen Pharmaceuticals; Financial Interests, Institutional, Research Grant: Dynavax; Financial Interests, Institutional, Research Grant: Eli Lilly; Financial Interests, Institutional, Research Grant: Elicio Therapeutics; Financial Interests, Institutional, Research Grant: EMD Serono; Financial Interests, Institutional, Research Grant: Erasca; Financial Interests, Institutional, Research Grant: Genentech/Roche; Financial Interests, Institutional, Research Grant: Genmab; Financial Interests, Institutional, Research Grant: Genocea Biosciences; Financial Interests, Institutional, Research Grant: GlaxoSmithKlein; Financial Interests, Institutional, Research Grant: Gritstone Oncology; Financial Interests, Institutional, Research Grant: Guardant Health; Financial Interests, Institutional, Research Grant: Harpoon; Financial Interests, Institutional, Research Grant: Helsinn Healthcare; Financial Interests, Institutional, Research Grant: Hengrui Therapeutics; Financial Interests, Institutional, Research Grant: Hutchinson MediPharma; Financial Interests, Institutional, Research Grant: IDEAYA Biosciences; Financial Interests, Institutional, Research Grant: IGM Biosciences; Financial Interests, Institutional, Research Grant: Immunocore; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Jounce Therapeutics; Financial Interests, Institutional, Research Grant: Kadmon Pharmaceuticals; Financial Interests, Institutional, Research Grant: Loxo Oncology; Financial Interests, Institutional, Research Grant: Lycera; Financial Interests, Institutional, Research Grant: Memorial-Sloan Kettering; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Mirati Therapeutics; Financial Interests, Institutional, Research Grant: NeoImmune Tech; Financial Interests, Institutional, Research Grant: Neovia Oncology; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Numab Therapeutics; Financial Interests, Institutional, Research Grant: Nuvalent; Financial Interests, Institutional, Research Grant: OncoMed Pharmaceuticals; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: PMV Pharmaceuticals; Financial Interests, Institutional, Research Grant: Rain Therapeutics; Financial Interests, Institutional, Research Grant: RasCal Therapeutics; Financial Interests, Institutional, Research Grant: Regeneron Pharmaceuticals; Financial Interests, Institutional, Research Grant: Relay Therapeutics; Financial Interests, Institutional, Research Grant: Revolution Medicine; Financial Interests, Institutional, Research Grant: Ribon Therapeutics; Financial Interests, Institutional, Research Grant: Rubius Therapeutics; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Seven and Eight Biopharmaceuticals; Financial Interests, Institutional, Research Grant: Shattuck Labs; Financial Interests, Institutional, Research Grant: Silicon Therapeutics; Financial Interests, Institutional, Research Grant: StemCentRx; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Tarveda; Financial Interests, Institutional, Research Grant: TCR2 Therapeutics; Financial Interests, Institutional, Research Grant: Tempest Therapeutics; Financial Interests, Institutional, Research Grant: Tizona Therapeutics; Financial Interests, Institutional, Research Grant: Tmunity Therapeutics; Financial Interests, Institutional, Research Grant: Turning Point Therapeutics; Financial Interests, Institutional, Research Grant: University of Michigan; Financial Interests, Institutional, Research Grant: Vyriad; Financial Interests, Institutional, Research Grant: WindMIL; Financial Interests, Institutional, Research Grant: Y-mAbs Therapeutics; Financial Interests, Institutional, Other, Consulting: AbbVie; Financial Interests, Institutional, Other, Consulting: Amgen; Financial Interests, Institutional, Other, Consulting: Astellas; Financial Interests, Institutional, Other, Consulting: AstraZeneca; Financial Interests, Institutional, Other, Consulting: Axelia Oncology; Financial Interests, Institutional, Other, Consulting: Black Diamond; Financial Interests, Institutional, Other, Consulting: Boehringer Ingelheim; Financial Interests, Institutional, Other, Consulting: Bristol Myers Squibb; Financial Interests, Institutional, Other, Consulting: Calithera; Financial Interests, Institutional, Other, Consulting: CytomX; Financial Interests, Institutional, Other, Consulting: Daiichi Sankyo; Financial Interests, Institutional, Other, Consulting: EcoR1; Financial Interests, Institutional, Other, Consulting: Editas Medicine; Financial Interests, Institutional, Other, Consulting: Eisai; Financial Interests, Institutional, Other, Consulting: EMD Serono; Financial Interests, Institutional, Other, Consulting: G1 Therapeutics; Financial Interests, Institutional, Other, Consulting: Genentech/Roche; Financial Interests, Institutional, Other, Consulting: Genmab; Financial Interests, Institutional, Other, Consulting: GlaxoSmithKlein; Financial Interests, Institutional, Other, Consulting: Gritstone Oncology; Financial Interests, Institutional, Other, Consulting: Ideaya Biosciences; Financial Interests, Institutional, : iTeos. M. Reck: Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Beigene; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Boehringer-Ingelheim; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Sanofi. Y. Zhang: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. D. Jandial: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. S. Cheng: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. L. Paz-Ares: Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: PharmaMar; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: PharmaMar; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Servier; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Mirati; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Mirati; Financial Interests, Personal, Leadership Role: Genomica; Financial Interests, Personal, Leadership Role: Altum sequency.