PS3-3 Clinical and biomarker data from a phase 1/2 trial of ifinatamab deruxtecan (I-DXd; DS-7300) in advanced solid tumors

Document Type

Conference Proceeding

Publication Date

10-1-2024

Publication Title

Ann Oncol

Abstract

Background: I-DXd, a novel B7 homolog 3 (B7-H3)–directed antibody–drug conjugate, leverages the clinically validated deruxtecan (DXd) technology with a plasma-stable linker and a potent topoisomerase I inhibitor payload. This analysis of an ongoing global first-in-human phase 1/2 trial (NCT04145622) includes tumor type subset data in small cell lung cancer (SCLC), esophageal squamous cell carcinoma (ESCC), castration-resistant prostate cancer (CRPC), and squamous non-small cell lung cancer (sqNSCLC) in addition to Japanese subset data. Methods: Efficacy was analyzed in patients treated with I-DXd at doses of 4.8–16.0 mg/kg, and safety was analyzed in all patients dosed. Response was evaluated per RECIST v1.1 in patients with ≥2 post-baseline scans or discontinuation for any reason. B7-H3 level was evaluated retrospectively, as patients were not pre-selected by baseline expression. Results: As of Jan 31, 2023, 8/144 patients remained on treatment. Safety data (N=174) were consistent with previous reports. I-DXd showed a promising objective response rate (SCLC: 11/21 [52%]; ESCC: 6/28 [21%]; CRPC: 15/59 [25%]; sqNSCLC: 4/13 [31%]) and durable response (median duration of response [95% CI] in months (SCLC: 5.9 [2.8–7.5]; ESCC: 3.5 [2.4–not estimable (NE)]; CRPC: 6.4 [3.0–10.0]; sqNSCLC: 4.1 [2.8–NE]). Median overall survival to date is encouraging (in months, SCLC: 12.2 [95% CI: 6.4–NE; n=21]; ESCC: 7.0 [95% CI: 4.8–12.2; n=28]; CRPC: 13.0 [95% CI: 10.3–16.0; n=73]; sqNSCLC: not reported). B7-H3 expression was moderate to high in most patients; correlation between response and B7-H3 level will be presented for SCLC and mCRPC cohorts. Analysis of a subset of Japanese patients will also be presented. Conclusions: I-DXd continues to demonstrate a manageable safety profile and promising antitumor activity in these heavily pretreated patients, which warrants further clinical evaluation. Clinical trial identification: NCT04145622. Legal entity responsible for the study: Daiichi Sankyo Co., Ltd. Funding: This study is sponsored by Daiichi Sankyo, Inc. In October 2023, Daiichi Sankyo entered into a global development and commercialization collaboration agreement with Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA for ifinatamab deruxtecan (I-DXd). Disclosure: T. Doi: Dr Doi has received advisory fees from Rakuten Medical, lecturer fees from Daiichi Sankyo, and research expenses from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Taiho Pharmaceutical, Boehringer Ingelheim, Daiichi Sankyo, Pfizer, Bristol Myers Squibb, AbbVie, Eisai, Janssen Pharmaceutical, Chugai Pharmaceutical, PRA Health Science, Ono Pharmaceutical, Shionogi, Amgen, GSK, RIN Institute. M. R Patel: Dr Patel holds a leadership position with ION Pharma, has received honoraria from Jannsen Oncology, serves in a consulting or advisory role for Olema Pharmaceuticas, Daiichi Sankyo, Kura Oncology, and Accutar Biotech, and has received research funding for his institution from Daiichi Sankyo, Acerta Pharma, ADC Therapeutics, Agenus, AstraZeneca, BioNTech AG, Boehringer Ingelheim, Bristol-Myers Sqibb/Celgene, Cyteir Therapeutics, Lilly, Genentech/Roche, Gilead Sciences, GlaxoSmithKline, H3 Biomedicine, Hengrui Therapeutics, Hutchison MediPharma, Janssen, Klus Pharma, Kymab, Loxo, LSK Biopartners, Macrogenics, Merck, Millennium, Moderna Therapeutics, Pfizer, Prelude Therapeutics, Ribon Therapeutics, Seven and Eight Biopharmaceuticals, Syndax, Taiho Pharmaceutical, Tesaro, ORIC, Artios, Mabspace, Puretech, BioTheryX, Novartis, Nurix, TeneoBio, Treadwell Therapeutics, Zymeworks, Olema, Adagene, Astellas, Accutar Biotech, Compugen, Immunogen, Blueprint Pharmaceuticals, Cullinan Oncology, Erasci, In, Immune-Onc Therapeutics, Immunitas, Pionyr, Step Pharma, Incyte, Kineta, Hotspot Therapeutics, Conjupro Biotherapeutics, Allorion Therapeutics, Vividion Therapeutics, Georgiamune, and Kura Oncology. T. Koyama: Dr Koyama has financial interests with Chugai, Sysmex, and Astra Zeneca, Eli Lilly, Pfi er, Janssen Pharma, Daiichi-Sankyo, Takeda, Zymworks, and Novartis and has participated in Speaker's bureau for Chgai, Sysmex, and AstraZeneca. He has received research grants from Chugai, AstraZeneca, Eli Lilly, Pfizer, Janssen Pharma, Daiichi-Sankyo, Takeda, Zymworks, and Novartis. G. S Falchook: Dr Falchook has personal royalties with Wolters Kluwer. Dr Falchook has received advisory fees from AbbVie, Fujifilm, Silicon, Navire, Turning Point, Predicine, Inspirna, Regeneron, Jubilant, BostonGene, Teon, Merck, Sanofi, BridgeBio and speaker fees for Total Health Conferencing, Rocky Mountain Oncology Society. Has received travel grants from Amgen, Bristol-Myers Squibb, EMD Serono, Fujifilm, Millennium, Sarah Cannon Research Institute (employer, at least once yearly), Synthorx/Sanofi and funding from 3-V Biosciences, Abbisko, Abbvie, ABL Bio, ADC Therapeutics, Accutar, Agenus, Aileron, American Society of Clinical Oncology, Amgen, ARMO/Eli Lilly, Artios, AstraZeneca, Bayer, BeiGene, Bioatla, Bioinvent, Biothera, Bicycle, Black Diamond, Boehringer Ingelheim, Celgene, Celldex, Ciclomed, Curegenix, Curis, Cyteir, Daiichi, DelMar, eFFECTOR, Eli Lilly, EMD Serono, Epizyme, Erasca, Exelixis, Freenome, Fujifilm, Genmab, GlaxoSmithKline, Hutchison MediPharma, IGM Biosciences, Ignyta, Immunitas, ImmunoGen/MacroGenics, Incyte, Jacobio, Jazz, Jounce, Jubilant, Kineta, Kolltan, Loxo/Bayer, MedImmune, Merck, Metabomed, Millennium, Mirati, miRNA Therapeutics, Molecular Templates, National Institutes of Health, Navire/BridgeBio, NGM Bio, NiKang, Novartis, OncoMed, Oncorus, Oncothyreon, Poseida, Precision Oncology, Prelude, PureTech, Pyramid, Pyxis, RasCal, Regeneron, Relay, Rgenix, Ribon, Roche, Samumed, Sapience, Seagen, Silicon, Simcha, Sirnaomics, Strategia, Syndax, Synthorx/Sanofi, Taiho, Takeda, Tallac, Tarus, Tarveda, Teneobio, Tesaro, Tocagen, Turning Point, U.T. MD Anderson Cancer Center, Vegenics, Xencor, Zhuhai Yufan. C. Friedman: Dr Friedman has financial interests with Merck, Seagen, Aadi Biosciences, Merdana, Astra Zeneca, Genentech/ Roche, Hotspot Therapeutics and Marengo. S. A Piha-Paul: Dr Piha-Paul has received funding from Abbvie, ABM Therapeutics, Acepodia, Alkermes, Aminex Therapeutics, Amphivena Therapeutics, BioMarin Pharma, Boehringer Ingelheim, Bristol Mysers Squib, Cerulean Pharma, Chugai Pharma Co, Curis, Cyclavel Pharma, Daiichi Sankyo, Eli Lilly, ENB Therapeutics, Epigenetix, Five Prime Therapeutics, F-Star Beta Limited, F-Star Therapeutics, GeneQuantum Healthcare, Genmab A/S, Gilead Sciences, Glaxo Smith Kline, Helix BioPharma Corp, Hengrui Pharma, HiberCell, Immorna Bio-therapeutics, Immunomedics, Incyte Corp, Jacobio Pharma Co, Jiangsu Simcere Pharma Co, Lytix Biopharma, Medimmune LLC, Medivation, Merck Sharp and Dohme Corp, Nectin Therapeutics, Novartis Pharma, Pieris Pharma, Pfizer, Phanes Therapeutics, Principa Biopharma, Purinomia Biotech, Rapt Therapeutics, Replimune, Seatte Genetics, Silverback Therapeutics, Synlogic Therapeutics, Taiho Oncology, CRC Oncology, Tesaro, TransThera Bio, ZielBio. M. Gutierrez: Dr Gutierrez has received consulting fees from Celularity and Guardant. M. Awad: Dr Awad has been a consultant for Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, Blueprint Medicine, Syndax, Ariad, Nektar, Mirati, NextCure, Novartis, EMD Serono, and received research funding from AstraZeneca, Lilly, Genentech, Bristol-Myers Squibb, Amgen, Turning Point Therapeutics. T. Satoh: Dr Satoh has financial interests with Daiichi-Sankyo, Eli-Lilly, Bristol-Myers, Ono Pharmaceutical, Hutch-Med, Amgen, Taiho Pharmaceutical. S. Takahashi: Dr Takahashi has received funding from DaiichiSankyo, and lecture fees from Eisai, MSD, Ono-pharmaceutical. S. Kadowaki: Dr Kadowaki has received funding from Sanofi and research expenses from Bayer. N. Okamoto: Dr Okamoto is employed by Daiichi Sankyo. H. Goto: Dr Goto is employed by Daiichi Sankyo Inc. N. Yoshizuka: Dr Yoshizuka is employed by Daiichi Sankyo Inc. M. Qian: Dr Qian is employed by Daiichi Sankyo Inc. X. Qian: Dr Qian is employed by Daiichi Sankyo Inc. M. J hnson: Dr Johnson has received research funding from AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAtla, Black Diamond, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera Biosciences, Carisma Therapeutics, Checkpoint Therapeutics, City of Hope National Medical Center, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Dynavax, Lilly, Elicio Therapeutics, EMD Serono, EQRx, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchison MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunitas Therapeutics, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Kartos Therapeutics, Loxo Oncology, Lycera, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, Mythic Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Palleon Pharmaceuticals, Pfizer, PMV Pharmaceuticals, Rain Therapeutics, 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 Therapeutics, Y-mAbs Therapeutics. Dr Johnson has received consulting/ advisory fees from AbbVie, Amgen, Arcus Biosciences, Arrivent, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Calithera Biosciences, Daiichi Sankyo, EcoR1, Genentech / Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Ideaya Biosciences, Immunocore, iTeos, Janssen, Jazz Pharmaceuticals, Merck, Mirati Therapeutics, Molecular Axiom, Novartis, Oncorus, Pyramid Biosciences, Regeneron Pharmaceuticals, Revolution Medicines, Sanofi-Aventis, SeaGen, Synthekine, Takeda Pharmaceuticals, Turning Point Therapeutics, VBL Therapeutics: All other authors have declared no conflicts of interest.

Volume

35

First Page

S1315

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