690P - Ifinatamab deruxtecan (I-DXd; DS-7300) in patients with advanced solid tumors: Updated clinical and biomarker results from a phase I/II study

Background

I-DXd is a novel B7-H3–directed antibody–drug conjugate that leverages the clinically validated deruxtecan (DXd) technology with a plasma-stable linker and potent topoisomerase I inhibitor payload. Here we present a follow-up analysis (7 mo since last report) of an ongoing phase 1/2 trial that includes heavily pretreated patients with castration-resistant prostate cancer (CRPC), esophageal squamous cell carcinoma (ESCC), squamous non-small cell lung cancer (sqNSCLC), and small cell lung cancer (SCLC). DOR, OS, and B7-H3 correlations with response are reported for the first time for CRPC, ESCC, and sqNSCLC.

Methods

Efficacy and safety were analyzed in patients treated with I-DXd at 4.8 to 16.0 mg/kg. Response was evaluated in patients with ≥2 postbaseline scans or discontinuation for any reason. Fourteen patients with CRPC lacked measurable target lesions at baseline (BL) and were excluded from ORR analysis. B7-H3 level was evaluated retrospectively as patients were not pre-selected by BL expression.

Results

As of 31 Jan 2023, 8 patients remained on treatment. Safety data were consistent with previous reports. I-DXd still demonstrated promising ORR results, including in an updated sample size for sqNSCLC (Table). Even in this heavily pretreated population, I-DXd exhibited durable response and encouraging early OS (Table), although further follow-up is needed. B7-H3 expression was moderate to high in most patients; no correlation was observed between response and B7-H3 level, and an update will be presented at the congress. Table: 690P

Efficacy

DOR, duration of response; NE, not estimable; NR, not reported; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; RECIST, Response Evaluation Criteria In Solid Tumors.

Conclusions

I-DXd continues to demonstrate a manageable safety profile and promising antitumor activity with encouraging DOR and OS in these heavily pretreated patients, which warrants further clinical evaluation across multiple indications.

Clinical trial identification

NCT04145622.

Editorial acknowledgement

Editorial assistance was provided by Matthew Simons, PhD, of BOLDSCIENCE.

Legal entity responsible for the study

Daiichi Sankyo, Inc.

Funding

Daiichi Sankyo, Inc.

Disclosure

M.R. Patel: Other, Personal, Leadership Role: ION Pharma; Financial Interests, Personal, Speaker, Consultant, Advisor: Janssen Oncology; Other, Personal, Advisory Role: Olema Pharmaceuticals; Financial Interests, Institutional, Research Funding: Acerta Pharma, ADC Therapeutics, Agenus, Aileron Therapeutics, AstraZeneca, BioNTech AG, Boehringer Ingelheim, Celgene, CicloMed, Clovis Oncology, Cyteir Therapeutics, Daiichi Sankyo, Lilly, Evelo Therapeutics, Genentech/Roche, Gilead Sciences, GSK, H3 Biomedicine, Hengrui Therapeutics, Hutchison MediPharma, Jacobio, Janssen, Klus Pharma, Kymab, Loxo, LSK Biopartners, Lycera, Macrogenics, Merck, Millennium, Mirati Therapeutics, Moderna Therapeutics, Pfizer, Prelude Therapeutics, Ribon Therapeutics, Seven and Eight Biopharmaceuticals, Syndax, Taiho Pharmaceutical, Tesaro, TopAlliance BioSciences Inc., Vigeo, ORIC Pharmaceuticals, Artios, Treadwell Therapeutics, MabSpace Biosciences, IgM Biosciences, Puretech, BioTheryX, Black Diamond Therapeutics, IgM Biosciences, NGM Biopharmaceuticals, Novartis, nurix, PureTech, Relay Therapeutics, Samumed, Silicon Therapeutics, TeneoBio, Zymeworks, Olema, Adagene, Astellas, NGM, Accutar Biotech, Nurix, Novartis, Compugen, Black Diamond Therapeutics, Relay Therapeutics, Artios, Immunogen, Blueprint Pharmaceuticals, Accutar, Bayer, Bicycle Therapeutics, BioTheryX, Compugen, Cullinan Oncology, Erasca, Inc., Immune-Onc Therapeutics, Immunitas, Jazz Pharmaceuticals, NGM Biopharmaceuticals, Novartis, Pionyr, Revolution Medicines, Ribon Therapeutics, Step Pharma, Syndax, Synthorx, Xencor. T. Doi: Other, Personal, Advisory Role: A2 Healthcare, Boehringer Ingelheim, Chugai Pharmaceutical, Gilead, Kaken Pharmaceutical, Kyowa Kirin, Nano Carrier, Noile-Immune Biotech, Oncolys BioPharma, Otsuka Pharmaceutical, PRA Health Sciences, Rakuten Medical, Shionogi, Sumitomo Pharma, Takeda; Other, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: AbbVie, Amgen, Bristol Myers Squibb, Boehringer Ingelheim, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, GSK, Janssen Pharmaceuticals, MSD, ONO Pharma, Pfizer, PRA Health Sciences, RIN Institute, Shionogi, Taiho. T. Koyama: Financial Interests, Personal, Speaker’s Bureau: Chugai, Sysmex, AstraZeneca; Financial Interests, Institutional, Research Grant: Chugai, AstraZeneca, Eli Lilly, Pfizer, Janssen Pharmaceuticals, Daiichi Sankyo, Takeda, Zymeworks, Novartis. G.S. Falchook: Financial Interests, Institutional, Advisory Board, 2018 : FujiFilm; Financial Interests, Institutional, Advisory Board, 7/24/2020, 9/17/2021: Silicon; Financial Interests, Institutional, Advisory Board, 3/10/21: Navire; Financial Interests, Institutional, Advisory Board, 4/22/21: Turning Point; Financial Interests, Institutional, Advisory Board, 10/2/21: Predicine; Financial Interests, Institutional, Advisory Board, 10/26/21: Inspirna; Financial Interests, Institutional, Advisory Board, 10/28/21: Regeneron; Financial Interests, Personal, Advisory Board, 6/2010, 3/2011: EMD Serono; Financial Interests, Institutional, Advisory Board, 1/18/22 and 8/17/22: Jubilant; Financial Interests, Institutional, Advisory Board, 6/4/22: BostonGene; Financial Interests, Institutional, Advisory Board, 9/30/22: AbbVie; Financial Interests, Personal, Invited Speaker, 2019 : Total Health Conferencing; Financial Interests, Personal, Invited Speaker, 2020 : 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, to present research at a conference (Cholangiocarcinoma Foundation meeting), 2018: Fujifilm; Financial Interests, Personal, Other, Travel, to present research at a conference (ESGO), 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, Other, Travel, to present research at a conference (WCLC), 2022: Amgen; Financial Interests, Personal, Other, Travel, to present research at a conference (ESMO), 2022: Synthorx / Sanofi; Financial Interests, Institutional, Advisory Board, Scientific advisory board 11/18/22: Teon Therapeutics; Financial Interests, Institutional, Advisory Board, 12/8/22: Merck; Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Institutional, Local PI: 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, Boehringer Ingelheim, Celldex, Celgene, Ciclomed, Curegenix, Curis, Cyteir, Daiichi Sankyo, DelMar, eFFECTOR, Eli Lilly, EMD Serono, Epizyme, Erasca, Exelixis, GSK, Freenome, Fujifilm, Genmab, Hutchison MediPharma, IGM Biosciences, Ignyta, ImmunoGen/MarcoGenics, Incyte, Jacobio, Jounce, Kolltan, Loxo/Bayer, MedImmune, Millennium, Merck, miRNA Therapeutics, Molecular Templates, National Institutes of Health, Navire, NiKang, Novartis, OncoMed, Oncorus, Oncothyreon, Poseida, Precision Oncology, Prelude, PureTech, Pyramid, RasCal, Regeneron, Rgenix, Ribon, Samumed, Sapience, Silicon, Simcha, Strategia, Syndax, Synthorx/Sanofi, Taiho, Takeda, Tarveda, Teneobio, Tesaro, Tocagen, Turning Point, U.T. MD Anderson Cancer Center, Vegenics, Xencor; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial: Black Diamond, Jubilant, Relay, Seagen, Sirnaomics, Metabomed, Agenus, Tallac, Zhuhai Yufan, Mirati, Immunitas, Jazz Pharmaceuticals, Bayer. C.F. Friedman: Financial Interests, Personal and Institutional, Principal Investigator, Both financial and non-financial interests: Merck, Genentech/Roche; Financial Interests, Personal and Institutional, Advisory Role, Both financial and non-financial interests: Merck, Genentech/Roche; Financial Interests, Personal and Institutional, Advisory Board: Seagen, Aadi Biosciences; Financial Interests, Personal and Institutional, Principal Investigator: Seagen; Financial Interests, Personal and Institutional, Advisory Board, Scientific advisory board; both financial and non-financial interests: Merck, Genentech/Roche; Financial Interests, Institutional, Principal Investigator: Mersana, AstraZeneca, Hotspot Therapeutics, Marengo. S.A. Piha-Paul: Financial Interests, Institutional, Funding: AbbVie, Inc., ABM Therapeutics, Inc., Acepodia, Inc., Alkermes, Aminex Therapeutics, Amphivena Therapeutics, Inc., BioMarin Pharmaceutical, Inc., Boehringer Ingelheim, Bristol Myers Squibb, Cerulean Pharma, Inc., Chugai Pharmaceutical Co., Ltd., Curis, Inc., Cyclacel Pharma, Daiichi Sankyo, Inc., Eli Lilly, ENB Therapeutics, Epigenetix, Inc., Five Prime Therapeutics, F-Star Beta Limited, F-Star Therapeutics, Limited, GeneQuantum Healthcare, Genmab A/S, Gilead Sciences, Inc., GSK, Helix BioPharma Corp., Hengrui Pharma, Co., Ltd., HiberCell, Inc., Immorna Bio-therapeutics, Inc., Immuno-medics, Inc., Incyte Corp., Jacobio Pharma Co., Ltd., Jiangsu Simcere Pharma Co., Ltd., Lytix Biopharma AS, Medimmune, LLC., Medivation, Inc., Merck Sharp and Dohme Corp., Nectin Therapeutics, Ltd., Novartis Pharmaceuticals, Pieris Pharma, Inc., Pfizer, Phanes Therapeutics, Principia Biopharma, Inc., Puma Biotechnology, Inc., Purinomia Biotech, Inc., Rapt Therapeutics, Inc., Replimune, Seattle Genetics, Silverback Therapeutics, Synlogic Therapeutics, Taiho Oncology, Tesaro, Inc., TransThera Bio, ZielBio, Inc., NCI/NIH P30CA016672-Core Grant; Financial Interests, Institutional, Advisory Role: CRC Oncology. M. Gutierrez: Financial Interests, Personal, Invited Speaker: Guardant Health; Financial Interests, Personal, Other, Consultant: MERCK; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Stocks/Shares: COTA Healthcare; Financial Interests, Institutional, Local PI: Merck, BMS, Incyte, NexCure, Pfizer, Roche/Genentech, Boehringer Ingelheim, GSB Pharma, Moderna, Eisai, Silenseed, Seattle Genetics, Regeneron, Sanofi, Johnson & Johnson, MedImmune, Checkpoint Therapeutics, Acerta Pharmaceuticals, Arcus Biosciences, Array BioPharma, Bayer, Celgene, Compass Therapeutics, Constellation Pharmaceuticals, Cyter, EMD Sereno, Fate Therapeutics, GSK, Infinity, Pharmacyclics, Synlogic, Tesaro, Vedanta. M.M. Awad: Financial Interests, Personal, Speaker, Consultant, Advisor: Genentech, Bristol Myers Squibb, Merck, AstraZeneca, Blueprint Medicine, Syndax, Ariad, Nektar, Mirati, NextCure, Novartis, EMD Serono; Financial Interests, Institutional, Research Funding: AstraZeneca, Lilly, Genentech, Bristol Myers Squibb, Amgen, Turning Point Therapeutics. T. Satoh: Financial Interests, Personal and Institutional, Invited Speaker: Daiichi Sankyo, Eli Lilly, Bristol Myers Squibb, Ono Pharmaceutical; Financial Interests, Personal and Institutional, Research Grant: Daiichi Sankyo, Eli Lilly, Bristol Myers Squibb, Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: HUTCHMED, Amgen, Taiho Pharmaceutical. J. Singh: Financial Interests, Personal and Institutional, Full or part-time Employment: Daiichi Sankyo Inc.; Financial Interests, Personal and Institutional, Stocks/Shares: Daiichi Sankyo Inc. N. Yoshizuka: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo Inc.; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo Inc. M. Qian: Financial Interests, Institutional, Member: Daiichi Sankyo. X. Qian: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo Inc.; Financial Interests, Personal, Stocks or ownership: Daiichi Sankyo Inc. B.P. Tran: Financial Interests, Institutional, Full or part-time Employment: Daiichi Sankyo, Inc. M.L. Johnson: Financial Interests, Institutional, Other, Consulting: AbbVie, Amgen, Arcus Biosciences, Arrivent, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Calithera Biosciences, Daiichi Sankyo, EcoR1, Genentech/Roche, Genmab, Genocea Biosciences, GSK, 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, VBL Therapeutics, Synthekine, Takeda Pharmaceuticals, Turning Point Therapeutics; Financial Interests, Institutional, Research Grant: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, Black Diamond, BeiGene, BerGenBio, BioAtla, 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, GSK, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchinson MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunitas Therapeutics, Jounce Therapeutics, Immunocore, Incyte, Janssen, Kadmon Pharmaceuticals, Kartos Therapeutics, Loxo Oncology, Lycera, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, Mythic Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent; Financial Interests, Institutional: OncoMed Pharmaceuticals. All other authors have declared no conflicts of interest.