610O - Preliminary results from a phase I, first-in-human study of DS-9606a, a claudin 6 (CLDN6)-directed antibody-drug conjugate (ADC), in patients (pts) with tumor types known to express CLDN6

Background

CLDN6, a component of cell-to-cell tight junctions, is nearly absent in normal adult tissue but overexpressed and associated with poor prognosis in several tumor types. DS-9606a is the first ADC composed of a humanized anti-CLDN6 antibody, cleavable linker, and pyrrolobenzodiazepine payload. This is the first report from the dose-escalation part of an ongoing Phase 1 trial of DS-9606a in pts with locally advanced/metastatic solid tumors (NCT05394675).

Methods

In dose escalation, adult pts (not selected based on tumor CLDN6 expression) with ECOG PS ≤1 who progressed on/were intolerant to standard therapies, receive DS-9606a IV Q3W at 0.016–0.225 mg/kg. Primary objectives are to evaluate safety and determine the maximum tolerated dose (MTD) and recommended dose(s) for expansion (RDE).

Results

At data cutoff (Feb 24, 2024), 40 pts had been treated and were included in the safety analysis, of whom 15 (38%) remained on treatment. Any-grade treatment-related treatment-emergent adverse events (TRTEAEs) occurred in 21 (53%) pts (Grade ≥3, 5%; two cases of Grade 3 anemia). The most common any-grade TRTEAEs were nausea (18%), fatigue (15%), and anemia (13%). There were no cases of ILD/pneumonitis. TEAEs requiring dose interruption (delay) were reported in 8 (20%) pts. There were no TEAEs requiring dose reduction or treatment withdrawal, or leading to death. Baseline characteristics are presented (Table). Preliminary analyses show confirmed objective responses (per RECIST v1.1) in germ-cell tumors (GCT) and gastric cancer; additional efficacy data will be presented. Table: 610O

^aMedian (range)

Conclusions

DS-9606a had a favorable safety profile, with no dose-limiting toxicity, dose-dependent increase in TEAEs or treatment discontinuations; preliminary efficacy is promising. MTD and RDE are not yet determined. Enrollment is ongoing.

Clinical trial identification

NCT05394675.

Editorial acknowledgement

Medical writing support was provided by David Buist, PhD, of BOLDSCIENCE®, Inc.

Legal entity responsible for the study

Daiichi Sankyo.

Funding

Daiichi Sankyo.

Disclosure

M.R. Patel: Financial Interests, Personal, Advisory Board: Daiichi, Janssen, Accutar; Financial Interests, Institutional, Local PI, research funding: Daiichi. E.P. Hamilton: Financial Interests, Institutional, Other, Consulting/Advisory Role: Genentech/Roche, Novartis, Lilly, Pfizer, Mersana, Olema Pharmaceuticals, Stemline Therapeutics, AstraZeneca, Daiichi Sankyo, Ellipses Pharma, Tubulis, Verascity Science, Theratechnologies; Financial Interests, Institutional, Other, Consulting: Accutar Biotechnology, Entos, Fosun Pharma, Gilead Sciences, Jazz Pharmaceuticals, Jefferies Llc, Medical Pharma Services, Tempus Labs, Zentalis Pharmaceuticals; Financial Interests, Institutional, Research Grant: Oncomed, Genentech/Roche, Zymeworks, Rgenix, Arqule, Clovis, Millennium, Acerta Pharma, Sermonix Pharmaceuticals, Black Diamond, Karyopharm, Curis, Syndax, Novartis, Boehringer Ingelheim, Immunomedics, FujiFilm, Taiho, Deciphera, Molecular Templates, Dana Farber Cancer Inst, Hutchinson MediPharma, MedImmune, SeaGen, Compugen, TapImmune, Lilly, Pfizer, H3 Biomedicine, Merus, Regeneron, Arvinas, StemCentRx, Verastem, eFfector Therapeutics, CytomX, InventisBio, Lycera, Mersana, Radius Health, AbbVie, Nucana, Leap Therapeutics, Zenith Epigenetics, Harpoon, Orinove, AstraZeneca, Tesaro, Macrogenics, EMD Serono, Daiichi Sankyo, Syros, Sutro, G1 Therapeutics, PharmaMar, Olema, Immunogen, Plexxicon, Amgen, Akesobio Australia, Shattuck Labs, ADC Therapeutics, Aravive, Atlas MedX, Ellipses Pharma, Incyte, Jacobio, Mabspace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pionyr Immunotherapeutics, Repertoire Immune Medicine, Treadwell Therapeutics, Accutar Biotechnology, Artios, BeiGene, Bliss BioPharmaceuticals, Cascadian Therapeutics, Context Therapeutics, Cullinan, Dantari, Duality Biologics, Elucida Oncology, Infinity Pharmaceuticals, K-Group Beta, Kind Pharmaceuticals, Loxo Oncology, Oncothyreon, Orum Therapeutics, Prelude Therapeutics, Profound Bio, Relay Therapeutics, Tolmar, Torque Therapeutics; Financial Interests, Institutional, Local PI: Bristol Myers Squibb, Eisai, Fochon Pharmaceuticals, Gilead Sciences, Inspirna, Myriad Genetic Laboratories, Silverback Therapeutics, Stemline Therapeutics. S.A. Piha-Paul: Financial Interests, Institutional, Principal Investigator: AbbVie, ABM Therapeutics, Acepodia, Alkermes, Aminex Therapeutic, BioMarin Pharmaceutical, Inc, Boehringer Ingelheim, Bristol Myers Squibb, Cerulean Pharma, Inc., Chugai Pharmaceutical Co., Ltd., Cullinan Oncology, Inc., Curis, Inc., Cyclacel Pharmaceuticals, Daiichi Sankyo, Inc., Eli Lilly, ENB Therapeutics, Epigenetix Inc., Five Prime Therapeutics, F-Star Beta, Ltd., F-Star Therapeutics, Ltd., GeneQuantum Healthcare, Genmab A/S, Gilead Sciences, Inc., GSK, Helix BioPharma Corp., Hengrui Pharmaceuticals, Co., Ltd., Hibercell, Inc., Immunomedics, Inc., Incyte Corp., Jacobio Pharmaceutical Co., Ltd., Jazz PHarmaceuticals, Jingsu Simcere Pharmaceutical Co., Ltd., Johnson & Johnson, Loxo Oncology, Inc., Lytix Biopharma AS, Medimmune, Llc., Medivation, Inc., Merck Sharp and Dohme Corp., Nectin Therapeutics, Ltd., Novartis Pharmaceuticals, NRG Oncology, Nurix, OncoNano Medicine, Inc., Pieris Pharmaceuticals, Inc., Pfizer, Phanes Therapeutics, Principia Biopharma, Inc., ProfoundBio, US Co., Puma Biotechnology, Inc., Purinomia Biotech, Inc., Rapt Therapeutics, Inc., Replimune, Roche/Blueprint, Seattle Genetics, Shasqi, Inc, Silverback Therapeutics, Synlogic Therapeutics, Taiho Oncology, Tallac Therapeutics, Inc., Tesaro, Inc., Theradex Oncology, Toragen Therapeutics, Inc., TransThera Bio, Xencor, Inc., ZielBio,Inc., NCI/NIH P30CA016672 - Core Grant (CCSG Shared Resources); Financial Interests, Institutional, Sponsor/Funding: AbbVie, ABM Therapeutics, Acepodia Inc, Aminex Therapeutic, Alkermes, BioMarin Pharmaceutical, Inc, Boehringer Ingelheim, Bristol Myers Squibb, Cerulean Pharma, Inc., Chugai Pharmaceutical Co., Ltd., Cullinan Oncology, Inc., Curis, Inc., Cyclacel Pharmaceuticals, Daiichi Sankyo, Inc., Eli Lilly, ENB Therapeutics, Epigenetix Inc., Five Prime Therapeutics, F-Star Beta, Ltd., F-Star Therapeutics, Ltd., GeneQuantum Healthcare, Genmab A/S, Gilead Sciences, Inc., GSK, Helix BioPharma Corp., Hengrui Pharmaceuticals, Co., Ltd., Hibercell, Inc., Immunomedics, Inc., Incyte Corp., Jacobio Pharmaceutical Co., Ltd., Jazz PHarmaceuticals, Jingsu Simcere Pharmaceutical Co., Ltd., Johnson & Johnson, Loxo Oncology, Inc., Lytix Biopharma AS, Medimmune, Llc., Medivation, Inc., Merck Sharp and Dohme Corp., Nectin Therapeutics, Ltd., Novartis Pharmaceuticals, NRG Oncology, Nurix, OncoNano Medicine, Inc., Pieris Pharmaceuticals, Inc., Pfizer, Phanes Therapeutics, Principia Biopharma, Inc., Puma Biotechnology, Inc., Purinomia Biotech, Inc., Rapt Therapeutics, Inc., Replimune, Roche/Blueprint, Seattle Genetics, Shasqi, Inc, Silverback Therapeutics, Synlogic Therapeutics, Taiho Oncology, Tallac Therapeutics, Inc., Tesaro, Inc., Theradex Oncology, Toragen Therapeutics, Inc., TransThera Bio, Xencor, Inc., ZielBio,Inc.; Financial Interests, Institutional, Research Funding: ProfoundBio, US Co.; Financial Interests, Institutional, Funding: NCI/NIH P30CA016672 - Core Grant (CCSG Shared Resources). J. Henry: Financial Interests, Institutional, Local PI: Abbiscko Therapeutics, ABl bio, Accutar Biotech ADC therapeutics, Agenus, Aileron Therapeutics, Amgen Inc, Artios, AstraZeneca, Bayer, Bicycle Therapeutics, BioAlta, BioInvent Pharma, Biomea Fusion, Biosplice Therapeutics, Black Diamond Therapeutics, Boehringer, Centessa Pharmaceuticals, Cyteir, Daiichi Sankyo, Eli Lilly, Epizyme, Erasca, Exelixis, FujiFilm, GSK, HCA, Harbour Biomed, Hutchison MediPharma, ICON Plc, IGM Biosciences, Immuneering Corporation, Immunitas, Immunogen, Incyte, Ingelheim, Jazz Pharmaceuticals, Jacobio Pharmaceuticals, Jounce Pharma, Jubilant Therapeutics, Kineta, Kura Oncology, Loxo Oncology, Merck & Co, Metabomed, Mirati, Molecular Templates, Navire Pharma, Nikang Pharmaceuticals, NGM Bio, Oncorus, Phanes, Poseida, Prelude Therapeutics, PureTech, Pyxis, Pyramid, Rascal Therapeutics, Regeneron, Relay Therapeutics, Rgenix Inc, Roche, Ribon Therapeutics, Sapience, Sarah Cannon Development Innovations, Sarah Cannon Research Institute, Seagen, Simcha Therapeutics, Siranomics, Stingthera, Synthorx Inc, Tachyon Therapeutics, Takeda Pharmaceuticals, Tallac Therapeutics, Tarveda, Tesaro, Turning Point Pharma, Vista Therapeutics, Xencor; Financial Interests, Personal, Full or part-time Employment: Sarah Cannon Research Institute; Other, Personal, Other: Tarus Therapeutics; Financial Interests, Personal, Local PI: Teneothree. U. Banerji: Financial Interests, Personal, Advisory Board Member: Pegasy, Carrick Therapeutics; Financial Interests, Personal, Advisory Board: Pharmenable, Ellipses Pharma; Financial Interests, Personal, Full or part-time Employment, Employed by the Institute of Cancer Research: The Institute of Cancer Research; Financial Interests, Institutional, Research Grant, Investigator Initiated Trial: Carrick Therapeutics, Chugai, Verastem Oncology; Financial Interests, Institutional, Research Grant, Pre clinical grant: Verastem Oncology; Financial Interests, Institutional, Research Grant, Preclinical Research Grant: Avacta; Non-Financial Interests, Principal Investigator: Various pharma companies. H. Okada, N. Said, V. Chatikhine: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo. M. Qian, X. Zhang: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. E. Fontana: Financial Interests, Personal, Invited Speaker: Caris Life Science, Repair Therapeutics; Financial Interests, Personal, Other, Conference attendance: Sapience Pharma; Financial Interests, Personal, Invited Speaker, Conference Attendance: Bicycles Therapeutics; Financial Interests, Personal, Full or part-time Employment: Hospital Corporation of America (HCA) International; Financial Interests, Personal, Officer: EORTC; Financial Interests, Institutional, Coordinating PI: Repair Therapeutics, Amgen, Taiho Pharmaceutical; Financial Interests, Institutional, Local PI: Bicycle Therapeutics, Artios Pharma, Seagen, Nurix Therapeutics, BioNTech SE, Relay Therapeutics, Pfizer, Roche, Daiichi Sankyo, Gilead Science, Basilea Pharmaceutica, Jiangsu Hengrui Medicine, Mereo Biopharma, Hutchmed, Merus, Crescendo Biologics, GSK plc, BeiGene, Turning Point Therapeutics, Sapience Pharma, Arcus Bioscience, Exelixis, Nerviano Medica, Elipsees, Deciphera, Ribon Therapeutics. All other authors have declared no conflicts of interest.