453O - DS-7300 (B7-H3 DXd antibody-drug conjugate [ADC]) shows durable antitumor activity in advanced solid tumors: Extended follow-up of a phase I/II study

Background

B7-H3 overexpression correlates with poor prognosis in many cancers. DS-7300 is a B7-H3–directed ADC with a topoisomerase I inhibitor payload (DXd). The DS-7300 dose finding study (NCT04145622) showed that DS-7300 was generally well tolerated with early signs of antitumor activity. We present extended follow-up data for a larger cohort of participants (pt) with selected tumor types.

Methods

This Ph 1/2 first-in-human study of DS-7300 enrolled pts with tumors unselected for B7-H3 expression; 12.0 mg/kg was selected for the ongoing expansion Ph. Efficacy/safety analyses included pts in the 4.8- to 16.0-mg/kg cohorts; efficacy was evaluated in pts with ≥2 postbaseline scans or discontinuation for any reason.

Results

As of Jan 21, 2022, 127 pts (median age of 67 years; n=110 male) received DS-7300 (72 in dose escalation; 55 in dose expansion). Pts had a median 5 prior lines of therapy (range, 1-14). Treatment duration range was 0.1-54 weeks with 51 pts (40%) on treatment. Responses were observed in 30/91 evaluable pts (33%) in total (eg, 7/9 pts with SCLC, 2/5 with sqNSCLC, and 16/42 with mCRPC; Table). Among 6 pts with SCLC and a confirmed PR, median duration of response was 4.4 months (95% CI, 2.8-not reached). The overall safety profile is consistent with previously reported results; treatment-emergent adverse events (TEAEs) occurred in 124 pts (98%); the most common (>30%) were nausea (61%), infusion-related reaction (35%), and vomiting (31%). However, higher rates of serious and grade ≥3 TEAEs within a shorter median treatment duration were noted in the 16.0-mg/kg cohort than the 8.0- and 12.0-mg/kg cohorts. Table: 453O

^aAll tumor types; evaluable patients had ≥2 postbaseline scans or discontinuation for any reason; responses in endometrial cancer, esophageal squamous cell carcinoma, head and neck squamous cell carcinoma, mCRPC, SCLC, sqNSCLC. ^bIncludes 6 unconfirmed PRs; 3 still on treatment. mCRPC, metastatic castration-resistant prostate cancer; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumours; SCLC, small cell lung cancer; SD, stable disease; sqNSCLC, squamous non–small cell lung cancer.

Conclusions

DS-7300 continues to demonstrate evidence of durable antitumor activity in heavily pretreated pts with SCLC, sqNSCLC, and mCRPC. These data support further clinical development of DS-7300, including a Ph 2 dose-optimization study in SCLC (NCT05280470) with starting dose levels of 8 mg/kg and 12.0 mg/kg.

Clinical trial identification

NCT04145622.

Editorial acknowledgement

Medical writing support was provided by Meredith Rogers, MS, CMPP (The Lockwood Group, Stamford, CT, USA) Editorial support was provided in accordance with Good Publication Practice guidelines (ismpp.org/gpp3).

Legal entity responsible for the study

Daiichi Sankyo, Inc.

Funding

Daiichi Sankyo, Inc.

Disclosure

T. Doi: Financial Interests, Institutional, Research Grant, Funding/Principal Investigator: Lilly, MSD, Daiichi Sankyo, Taiho, Novartis, Merck Biopharma, Janssen Pharmaceutical, Boehringer Ingelheim, Pfizer, BMS, AbbVie, Eisai, Chugai Pharma; Financial Interests, Personal, Advisory Role, Consultancy: Janssen Pharmaceutical, Boehringer Ingelheim, Chugai Pharmaceutical, Rakuten Medical , KANEN Pharmaceutical, NanoCarrier , KYOWA KIRIN, Takeda Pharmaceutical , Otsuka Pharmaceutical, SHIONOGI, Sumitomo Pharma, PRA Health Science; Financial Interests, Personal, Invited Speaker: BMS, Ono Pharmaceutical, AstraZeneca, Daiichi Sankyo. M. Patel: Financial Interests, Personal, Speaker’s Bureau: Exelis, Genentech/Roche, Taiho Pharmaceutical, Celgene; Financial Interests, Personal, Advisory Board: Mirati, Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Pharmacyclics/Janssen, Pfizer/EMD Serono; Financial Interests, Personal, Other, Travel, accommodation, expenses: Pfizer, Pharmacyclics, Bayer; Non-Financial Interests, Institutional, Funding: Acerta Pharma, ADC Therapeutics, Agenus, Aileron Therapeutics, AstraZeneca, Bicycle Therapeutics, BioNTech AG, Blueprint, Boehringer Ingelheim, Calithera Biosciences, Celgene, Checkpoint Therapeutics, CicloMed, Clovs Oncology, Curis, Cyteir, Daiichi Sankyo, eFFECTOR Therapeutics, Lilly, EMD Serono, Evelo Therapeutics, FORMA Therapeutics, Genentech/Roche, Gilead, GSK, H3 Biomedicine, Hengrui Therapeutics, Hutchinson MediPharma, Ignyta, Jacobio, Janssen, Jounce Therapeutics, Klus Pharma, Kymab, Loxo, LSK BioPharma, Lycera, Merck, Millenium, Mirato Therapeutics, Pfizer, Phoenix Molecular Designs, Placon, Portola Pharmaceuticals, Prelude Therapeutics, QiLu Pharmaceuticals, PubGene, Revolution Medicines, Ribon Therapeutics, Seven and Eight Biopharmaceuticals, Syndax, Synthorx, Stemline Therapeutics, Taiho Pharmaceutical, Takea, TopAlliance Biosciences Inc, Vedanta Biosciences, Verastem, Vigeo Therapeutics, xencor, Artios, Treadwell Therapeutics, MadSpace Biosciences, IgM Biosciences, Puretech, Erasca Inc. G.S. Falchook: Financial Interests, Institutional, Advisory Board: FujiFilm, Silicon, Navire, Turning Point, Predicine, Inspirna, Regeneron; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Invited Speaker: Total Health Conferencing, Rocky Mountain Oncology Society; Financial Interests, Personal, Other, Travel, for work and/or research related to institution, 2015: Bristol-Myers Squibb; Financial Interests, Personal, Other, Travel, for work and/or research related to institution, 2011, 2012, 2013: EMD Serono; Financial Interests, Personal, Other, Travel, for work and/or research related to institution, 2018: Fujifilm; Financial Interests, Personal, Other, Travel, for work and/or research related to institution, 2013: Millennium; Financial Interests, Personal, Other, Travel, for work and/or research related to institution, at least once yearly: Sarah Cannon Research Institute (employer); Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Institutional, Invited Speaker: 3-V Biosciences, Abbisko, AbbVie, ABL Bio ADC Therapeutics, Accutar, Aileron, American Society of Clinical Oncology, Amgen, ARMO/Eli Lilly, Artios, AstraZeneca, BeiGene, Bioatla, Bioinvent, Biothera, Bicycle, Black Diamond, Boehringer Ingelheim, Celldex, Celgene, Ciclomed, Daiichi, Curegenix, Curis, Cyteir, DelMar, eFFECTOR, Eli Lilly, EMD Serono, Epizyme, Erasca, Exelixis, Freenome, Fujifilm, Genmab, GlaxoSmithKline, Hutchison MediPharma, IGM Biosciences, Ignyta, ImmunoGen/MarcoGenics, Incyte, Jacobio, Loxo/Bayer, Jounce, Jubilant, Kolltan, MedImmune, Millennium, Merck, miRNA Therapeutics, Molecular Templates, National Institutes of Health, Navire, NiKang, Novartis, OncoMed, Oncorus, Oncothyreon, Poseida, Pyramid, Precision Oncology, Prelude, PureTech, RasCal, Regeneron, Relay, Rgenix, Ribon, Samumed, Sapience, Seagen, Silicon, Simcha, Sirnaomics, Strategia, Syndax, Synthorx/Sanofi, Taiho, Takeda, Tarveda, Teneobio, Tesaro, Tocagen, Turning Point, U.T. MD Anderson Cancer Center, Vegenics, Xencor. T. Koyama: Financial Interests, Personal, Speaker’s Bureau: Chugai, Sysmex; Financial Interests, Institutional, Research Grant: PACT Pharma. C.F. Friedman: Non-Financial Interests, Personal, Advisory Board, (LYNK-002), Compensation Waived: Merck; Non-Financial Interests, Personal, Advisory Board, (My Pathway), Compensation Waived: Genentech; Non-Financial Interests, Personal, Principal Investigator: Daiichi Sankyo, Bristol Myers Squibb, Genentech/Roche , Merck, AstraZeneca; Financial Interests, Personal, Other, Personal Fees: Arch Oncology, Bristol Myers Squibb. S. Piha-Paul: Other, Institutional, Other, Clinical Trial Research Support through Institution: AbbVie, Inc., ABM Therapeutics, Inc., Acepodia, Inc, Alkermes, Aminex Therapeutics, Amphivena Therapeutics, Inc., BioMarin Pharmaceutical, Inc, Boehringer Ingelheim, Bristol Myers Squib, Cerulean Pharma, Inc., Chugai Pharmaceutical Co., Ltd, Cyclacel Pharmaceuticals, Daiichi Sankyo, Inc., Eli Lilly, ENB Therapeutics, Five Prime Therapeutics, F-Star Beta Limited, F-Star Therapeutics, Limited, Gene Quantum, Genmab A/S, Genmab A/S, Gilead Sciences, Inc., GlaxoSmithKline, Helix BioPharma Corp., HiberCell, Inc., Immunomedics, Inc., Incyte Corp., Jacobio Pharmaceuticals Co., Ltd., Lytix Biopharma AS, Medimmune, LLC., Medivation, Inc., Merck Sharp and Dohme Corp., Novartis Pharmaceuticals, Pieris Pharmaceuticals, Inc., Pfizer, Phanes Therapeutics, Principia Biopharma, Inc., Puma Biotechnology, Inc., Purinomia Biotech, Inc., Rapt Therapeutics, Inc., Seattle Genetics, Silverback Therapeutics, Synlogic Therapeutics, Taiho Oncology, Tesaro, Inc., TransThera Bio, ZielBio, Inc., NCI/NIH P30CA016672 – Core Grant (CCSG Shared Resources); Non-Financial Interests, Institutional, Other, Clinical Trial Research Support through Institution: Curis, Inc.; Other, Institutional, Other, Consultant: CRC Oncology. M. Awad: Financial Interests, Personal, Advisory Role: Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, Maverick, Blueprint Medicine, Syndax, Ariad, Nektar, ArcherDX, Mirati, NextCure, Novartis, EMD Serono; Financial Interests, Institutional, Funding: AstraZeneca, Lilly, Genentech, Bristol-Myers Squibbb. D.R. Adkins: Financial Interests, Institutional, Funding: Pfizer, Eli Lilly, Merck, Celgene/Bristol-Myers Squibb, Novartis, AstraZeneca, Blueprint Medicines, Kura Oncology, Exelixis, Matrix Biomed, Aduro Biotech, CUE Biopharma, Cofactor Genomics, Shanghai Denovo, Hookipa, Debio, Adlai Nortye, Beigene, Conjupro, Epizyme, Gilead, ISA, Roche, Rubius, Immutep, Tizona, Vaccinex, Genmab, Boehringer Ingelheim; Financial Interests, Institutional, Principal Investigator: Pfizer, Eli Lilly, Merck, Celgene/Bristol-Myers Squibb, Novartis, AstraZeneca, Blueprint Medicines, Kura Oncology, Exelixis, Matrix Biomed, Aduro Biotech, CUE Biopharma, Cofactor Geonomics, Shanghai Denovo, Hookipa, Debio, Adlai Nortye, Beigene, Conjupro, Epizyme, Gilead, ISA, Rocher, Rubius, Immutep, Tizona, Genmab, Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Merck, CUE Biopharma, Blueprint Medicines, Exelixis, Immunitas, Kura Oncology, TargImmune, Therapeutics, TwoXAR, Vaccinex, Xilio Therapeutics, Boehringer Ingelheim. S. Takahashi: Financial Interests, Personal, Invited Speaker: MSD, Eisai, Daiichi Sankyo, Chugai, Ono Pharmaceutical, Taiho, Bristol Myers Squibb, Eli Lilly; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Institutional, Principal Investigator: Tiaho, Daiichi Sankyo, Novartis, Ono Pharmaceutical, Eisai, IQVIA, Bristol Myers Squibb, Bayer, AstraZeneca. S. Kadowaki: Financial Interests, Personal, Invited Speaker: Taiho, Eli Lilly, MSD, Ono, Daichi Sankyo, BMS, Bayer, Merck Serono, Eisai; Financial Interests, Institutional, Funding: Taiho, Eli Lilly, MSD, Ono, Daichi Sankyo, Chugai, Nobelpharma, Yansen. B. Cheng: Financial Interests, Institutional, Stocks/Shares: Daiichi-Sankyo; Financial Interests, Institutional, Funding: Daiichi-Sankyo. N. Ikeda, A. Laadem, N. Yoshizuka: Financial Interests, Institutional, Stocks/Shares: Daiichi-Sankyo; Financial Interests, Institutional, Full or part-time Employment: Daiichi-Sankyo. M. Qian: Financial Interests, Institutional, Full or part-time Employment: Daiichi Sankyo; Financial Interests, Institutional, Stocks/Shares: Daiichi Sankyo. O. Dosunmu: Financial Interests, Institutional, Full or part-time Employment: Sarah Cannon Research Institute; Financial Interests, Institutional, Stocks/Shares, in Parent Company -HCA: Sarah Cannon Research Institute. H. Arkenau: Financial Interests, Personal, Invited Speaker: Servier, Guardant; Financial Interests, Personal, Advisory Board: iOnctura, Beigene; Financial Interests, Institutional, Invited Speaker: multiple small and large Pharma/Biotechs. M.L. Johnson: Financial Interests, Institutional, Research Grant, Funding: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAlta, 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, Gaurdant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchison MediPharma, IDEYA Biosciences, IGM Biosciences, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Loxo Oncology, Lycera, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Pfizer, PMV Pharmaceuticals, RasCal Therapeutics, Regeneron Pharmaceuticals , Rely 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, TMUNITY Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, WindMIL, Y-mAbs Therapeutics; Financial Interests, Personal, Research Grant, Funding: Gritstone Oncology, Tizona Therapeutics; Financial Interests, Institutional, Other, Consulting: Amgen, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera Biosciences, Checkpoint Therapeutics, CytomX Thyerapeutics, Daiichi Sankyo, EcoR1, Editas Medicine, Esai, EMD Serono, G1 Therapeutics, Genentech/Roche; Financial Interests, Institutional, : Genmab. All other authors have declared no conflicts of interest.