PO.CTP01.01 · 进行中的临床试验
A Phase 1a/1b, first-in-human study of an ADC targeting ADAM9 (DB-1317) in participants with selected advanced or metastatic solid tumors
作者与单位
摘要 Abstract
Background: A disintegrin and a metalloprotease 9 (ADAM9) is highly expressed in several cancer types and its expression level correlates with a suppressive tumor microenvironment, metastasis, and poor prognosis, making it a promising therapeutic target. DB-1317 is an antibody-drug conjugate (ADC) comprised of an anti-ADAM9 antibody linked to a topoisomerase I inhibitor via a cleavable tetrapeptide linker, with a drug-to-antibody ratio of approximately 8. Preclinical studies demonstrated that DB-1317 induced ADAM9-dependent cytotoxicity, exhibited both by-stander killing effect and antibody-dependent cellular cytotoxicity. In addition, DB-1317 is well-tolerated at a dose of up to 80 mg/kg in cynomolgus monkeys. These findings warrant clinical development of DB-1317 (Shengchao Lin, AACR 2025).
Methods: The first-in-human phase 1a/1b study (NCT07141706) aims to assess the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activities of DB-1317 in participants with selected unresectable advanced/metastatic solid tumors, without mandatory requirement for a minimum ADAM9 expression level. The study is planned to enroll approximately 223 participants from the United States, Australia, and China (up to 63 in phase 1a and approximately 160 in phase 1b).In phase 1a (dose escalation part), participants who have progressed on/after or are intolerant to standard treatments for advanced/unresectable or metastatic selected solid tumors will be enrolled to identify the maximum tolerated dose or maximum administered dose of DB-1317. Selected solid tumors include gastric cancer (GC), colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), cholangiocarcinoma, non-small cell lung cancer, and castrate-resistant prostate cancer. Approximately five ascending dose levels of DB-1317 (accelerated titration design for the first dose level and a BOIN design for subsequent dose levels) will be administered by intravenous infusion. The dose-limiting toxicities (DLT) will be assessed. When a dose level is confirmed to be safe by the Safety Monitoring Committee (SMC), backfill participants may be enrolled to further evaluate DB-1317. Phase 1b (dose expansion part) will include one randomized expansion cohort in GC and two single-arm expansion cohorts in CRC and PDAC, if preliminary anti-tumor activities in these tumor types are observed in phase 1a part. Dose levels used in phase 1b part will be determined by sponsor and SMC based on phase 1a data. As of Dec 24, 2025, 7 participants have been enrolled in Australia and the United States.
利益披露 Disclosure
C. Lemech, None..
A. Spira, None.
D. Sommerhalder,
IQVIA Stock Option.
Texas Oncology Employment.
Guidepoint; Nimbus Therapeutics; Revolution Medicines; Abbvie; Cartography Bio Independent Contractor.
Abbvie; Acrivon Therapeutics; ADC therapeutics; Alentis Therapeutics; Aprea Therapeutics; Ascentage Pharma; Astellas; AstraZeneca; Avenzo Therapeutics; Axion Bio Inc; Biomea Fusion; BioNTech ).
BJ Bioscience; Boehringer Ingelheim; Bristol Myers Squibb; Compugen; Day One Biopharmaceuticals; Dewpoint Therapeutics Inc; Dicerna Pharmaceuticals/Novo Nordisk; Exelixis; Fate Therapeutics ).
Gilead Sciences; GSK; Haihe Pharmaceutical; IconOvir Bio; Ideaya Biosciences; Immuneering; IMPACT Therapeutics; Incendia Therapeutics; Ipsen; Kura Oncology; Medlink Therapeutics ).
Mirati Therapeutics/Bristol Myers Squibb; ModeX Therapeutics; Monopteros Therapeutics; Navire Pharma;NGM Bio; Nimbus Therapeutics; Normunity Inc; OncoResponse; OBI Pharma ).
ProteinQure; Pfizer;ProteinQure;Revolution Medicines;Step Pharma;Sutro Biopharma ).
Symphogen; Systimmune; Tachyon Therapeutics; Teon Therapeutics; ).
Tyligand Bioscience;VelaVigo Pharma Co;Vincerx Pharma; Vividion Therapeutics ).
ZielBio;Zymeworks ).
S. Fu,
Abbisko; Antengene; BeiGene; BeyongSpring Pharmaceuticals, Inc.; LLC.; Biotheus Inc; Boehringer Ingelheim; Coherent Biopharma, LLC; Crossignal Therapeutics, Inc.; CUE Biopharma, Inc. ).
DEKA Biosciences; Eli Lilly & Co.; Exelixis; Fore Biotherapeutics; Greenfire Bio, Inc.; Hookipa Biotech; IMV, Inc.; Innovent Biologics, Co., Ltd.; Jazz Pharmaceuticlals; K-Group Beta; ).
Lantern Pharma Inc.; Lyvgen Biopharm, Co., Ltd.; MacroGenics; MediLink Therapeutics, Co. Ltd.; Millennium Pharmaceuticals, Inc.; Nerviano Medical Sciences; NeuPharma, Inc. ).
NextCure, Inc.; Ningbo NewBay Technology Development Co., Ltd.; Novartis; NovoCure; Nykode Therapeutics AS.; Parexel International, LLC; PharmaMar USA, Inc.; Pionyr Immunotherapeutics, Inc.; ).
PureTech Health, LLC; Qurgen, Inc.; Shanghai Huaota Biopharmaceutical Co., Ltd.; Sellas Life Sciences Group; Soricimed Biopharma, Inc.; SQZ Biotechnologies; Sumitomo Dainippon ).
Taiho Oncology and NCCN; Tigermed Group, LLC; TransCode Therapeutics, Inc.; Treadwell Therapeutics; Turnstone Biologics; Tyligand Bioscience, Ltd.; Virogin Biotech, Ltd. ).
Cancer Prevention Research Institute of Texas (CPRIT) Precision Oncology Decision Support Core (RP150535); Clinical and Translational Science Award Grant (CTSA) 1UM1TR0045906. ).
F. Ge,
Duality Biologics Employment.
H. Mu,
Duality Biologics Employment, Stock.
Y. Yang,
Duality Biologics Employment.
Y. Qiu,
Duality Biologics Employment, Stock.
J. Chen,
Duality Biologics Employment, Stock.
R. Shi,
Duality Biologics Employment, Stock.
Z. Zhu,
Duality Biologics g., Board of Directors, non-salaried role), Stock.
R. Xu, None.