Abstract 1550TiP
Background
ES-SCLC is highly aggressive and despite high response rates to first-line therapy, disease progression often occurs within 6 months. There are limited later-line therapeutic options for relapsed SCLC, indicating a significant unmet need for treatment with durable benefit in second line and beyond. B7 homolog 3 protein (B7-H3), a type 1 transmembrane protein in the B7 family, is overexpressed in many cancers, including SCLC, and correlated with poor prognosis. DS-7300 is a novel, antibody drug conjugate comprising a humanized anti-B7-H3 immunoglobulin G1 monoclonal antibody and potent topoisomerase I inhibitor payload (exatecan derivative, DXd) covalently linked by a stable tetrapeptide-based cleavable linker. DS-7300 (4.8-16.0 mg/kg) demonstrated promising clinical activity in an ongoing phase 1/2 first-in-human study, with 7/9 evaluable, heavily pretreated pts with SCLC achieving a response as of Jan 22, 2022. This study (NCT05280470) will define the recommended phase 2 dose and prospectively investigate efficacy of DS-7300 in ES-SCLC.
Trial design
This global, multicenter, phase 2 study will include pts with ES-SCLC who received 1 to 3 prior lines of therapy. Eighty pts will be randomized 1:1 (8 mg/kg or 12 mg/kg) and treated with DS-7300 intravenously on day 1 of each 21-day cycle until unacceptable toxicity, progressive disease, or consent withdrawal; an additional ∼60 pts may be enrolled at the recommended phase 2 dose after study steering committee consultation. The primary endpoint is objective response rate (ORR) assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. Secondary endpoints are progression-free survival, duration of response, disease control rate, and time to response assessed by the investigator and BICR based on RECIST v1.1; overall survival; ORR by investigator assessment based on RECIST v1.1; treatment-emergent adverse events and other safety parameters; plasma pharmacokinetic parameters for DS-7300, total anti-B7-H3, and DXd; and antidrug antibodies. Exposure-response and biomarkers analyses are exploratory endpoints. Estimated study completion is Jun 2024.
Clinical trial identification
NCT05280470.
Editorial acknowledgement
Medical writing support was provided by Meredith Rogers, MS, CMPP (The Lockwood Group, Stamford, CT, USA).
Legal entity responsible for the study
Daiichi Sankyo, Inc.
Funding
Daiichi Sankyo, Inc.
Disclosure
L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, BeiGene, Daiichii, 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, Invited Speaker: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme corp, BMS, Janssen-cilag international NV, NOvartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Other, Member: AACR, ASCO, ESMO; Financial Interests, Other, Foundation Board Member: AECC; Financial Interests, Other, President ASEICA (Spanish Association of Cancer Research): ASEICA; Financial Interests, Other, Foundation president: ONCOSUR; Financial Interests, Other, member: Small Lung Cancer Group. M.L. Johnson: Financial Interests, Institutional, Research Grant, Paid to Institution: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAtla, Boehringer Ingelheim, Calithera Biosciences, Checkpoint Therapeutics, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Dynavax, Lilly, Elicio Therapeutics, EMD Serono, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Gaurdant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchinson MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Loxo Oncology, Memorial Sloan Kettering, Merck , Merus, Mirati Therapeutics , NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals , Pfizer, PMV Pharmaceuticals, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, 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; Financial Interests, Institutional, Other, Consulting/Paid to Institution: AbbVie, Amgen, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera Biosciences, Checkpoint Therapeutics, Daiichi Sanyko, EcoR1, Editas Medicine, Esai , EMD Serono, G1 Therapeutics, Genentech/Roche, Genmab; Financial Interests, Institutional, : Genocea Biosciences. N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS; Non-Financial Interests, Officer, International Thymic Malignancy Interest Group, President: ITMIG; Other, Family member is an employee: AstraZeneca. C.L. Hann: Financial Interests, Institutional, Funding, Clinical Trial Fundig: AbbVie; Financial Interests, Personal and Institutional, Advisory Board, Clinical Trial Funding: Amgen, AstraZeneca, Genentech/Roche; Financial Interests, Institutional, Funding, Clinical Trial Funding: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker, Educational CME program: Janssen. M. Ahn: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Lilly, Takeda, Merck, MSD, Amgen, Yuhan, Daiichi-Sankyo, Roche, Pfizer; Financial Interests, Personal, Advisory Role, Advisory/Consultancy: AstraZeneca, Lilly, Takeda, Merck, MSD, Amgen, Yuhan, Daiichi-Sankyo, Roche, Pfizer, ARCUS, Alpha-pharmaceuticals. M. Nishio: Other, Personal, Other, Personal Fees: Ono, Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb, Daiichi Sankyo, Lilly, MSD, AbbVie, Boehringer Ingelheim, Nippon Kayaku, Takeda, Novartis, Janssen; Financial Interests, Personal and Institutional, Other, Grants/Personal Fees: AstraZeneca, Pfizer; Other, Personal, Other, Personal Fees/outside the submitted work: Tejin Pharma; Other, Personal, Other, Grants/Personal Fees: Merck. J. Godard: Financial Interests, Institutional, Full or part-time Employment: Daiichi-Sankyo; Financial Interests, Institutional, Stocks/Shares: Daiichi-Sankyo. A. Laadem: Financial Interests, Institutional, Full or part-time Employment: Daiichi-Sankyo; Financial Interests, Institutional, Stocks/Shares: Daiichi-Sankyo. N. Yoshizuka: Financial Interests, Institutional, Stocks/Shares: Daiichi-Sankyo; Financial Interests, Institutional, Full or part-time Employment: Daiichi-Sankyo. M. Qian: Financial Interests, Institutional, Stocks/Shares: Daiichi-Sankyo; Financial Interests, Institutional, Full or part-time Employment: Daiichi-Sankyo. B. Cheng: Financial Interests, Institutional, Full or part-time Employment: Daiichi-Sankyo; Financial Interests, Institutional, Stocks/Shares: Daiichi-Sankyo. C.M. Rudin: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Daiichi Sankyo, Epizyme, Genentech/Roche, Ipsen, Jazz, Kowa, Lilly, Merck, Syros, Bridge Medicines, Earli, Harpoon Therapeutics.