722TiP - CLAUDIO-01: A multicentric phase I/II trial to evaluate the safety and efficacy of SOT102 as monotherapy and in combination with standard of care (SoC) in patients with gastric, gastroesophageal junction(GEJ), and pancreatic adenocarcinoma

Background

SOT102 is an antibody-drug conjugate targeting CLDN18.2, based on a highly specific monoclonal antibody conjugated to PNU-159682, an anthracycline derivative, using site-specific conjugation technology. Preclinical data support the development of SOT102 in the clinical setting.

Trial design

CLAUDIO-01 is a multicenter, multimodular phase I/II trial in gastric/GEJ and pancreatic cancer patients in both advanced and first line. The trial consists of the following modules: • Part A: First-in-human, CLDN18.2 agnostic, single-agent dose escalation trial of SOT102 in advanced or metastatic gastric/GEJ or pancreatic cancer patients • Part B gastric, GEJ cohort/pancreatic cohort: CLDN18.2 agnostic dose escalation trial of SOT102 in combination with SoC for first-line treatment of patients with advanced or metastatic gastric/GEJ cancer (SoC: mFOLFOX with nivolumab) or pancreatic cancer (SoC: nab-paclitaxel/gemcitabine), which will start once monotherapy SOT102 dose level 3 in Part A is deemed safe The following expansion cohorts are planned upon identification of the recommended phase 2 dose (RP2D): • Part C gastric, GEJ/pancreatic cohort: Single-agent SOT102 in CLDN18.2 positive gastric/GEJ cancer patients after two or more prior systemic therapies and in pancreatic cancer after one or more prior systemic therapies. • Part D gastric, GEJ/pancreatic cohort: SOT102 in combination with SoC for first-line treatment in CLDN18.2 positive gastric/GEJ and pancreatic cancer patients Dose escalation follows an accelerated modified Fibonacci scheme with cohort sizes of 3+3 and includes safety observation periods. Monotherapy dose escalation is ongoing at the third dose level without dose-limiting toxicity. Enrollment to dose level 4 of Part A and to dose level 1 in both cohorts of Part B are planned to begin in June 2023. Primary objectives and endpoints: -To determine the MTD and RP2D of SOT102 as monotherapy and in combination with first-line SoC treatment (Parts A and B) - To assess the efficacy of SOT102 in monotherapy and in combination with first-line SoC treatment by ORR (Parts C and D).

Clinical trial identification

NCT05525286, 31 August 2022.

Editorial acknowledgement

Legal entity responsible for the study

SOTIO Biotech AG.

Funding

SOTIO Biotech AG.

Disclosure

R. Obermannova: Financial Interests, Personal, Advisory Board: BMS, Servier; Financial Interests, Personal, Invited Speaker: Merck, MSD; Non-Financial Interests, Leadership Role, Czech Clinical Trials Network in Oncology: CZECRINonco; Non-Financial Interests, Leadership Role, Visegrad 4 educational grant for clinical trials staff: Visegrad Funds. A. hollebecque: Financial Interests, Personal, Invited Speaker: Servier, Incyte, Eisai; Financial Interests, Personal, Advisory Board: Basilea, Tahio, Relay Theraeutics, QED Therapeutics, Debiopharm, MSD, Boehringer Ingelheim; Financial Interests, Institutional, Funding: Incyte; Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Principal Investigator, M19-345: AbbVie; Non-Financial Interests, Principal Investigator, CO42216; WP42627; CO40939: Roche; Non-Financial Interests, Principal Investigator, MCLA-158: Merus; Non-Financial Interests, Principal Investigator, SGNB6A: Seatle Genetics; Non-Financial Interests, Principal Investigator, TAS-120-202: Tahio; Non-Financial Interests, Principal Investigator, Krystal-10: Mirati; Non-Financial Interests, Principal Investigator, ADP-0033: Adaptimmune; Non-Financial Interests, Principal Investigator, ACT16902: Sanofi; Non-Financial Interests, Principal Investigator, C4201002: Pfizer; Non-Financial Interests, Principal Investigator, RLY-4008: Relay Therapeutics; Non-Financial Interests, Principal Investigator, CC-90011: Celgene/BMS; Non-Financial Interests, Principal Investigator, Loxo-IDH: Loxo/Lilly; Non-Financial Interests, Principal Investigator: AstraZeneca; Non-Financial Interests, Principal Investigator, SN-201 study: SOTIO; Non-Financial Interests, Principal Investigator, Tropics-03: Gilead; Non-Financial Interests, Principal Investigator, BI1403: Boehringer Ingelheim. T. Macarulla: Financial Interests, Personal, Advisory Board: Ability Pharmaceutical, SL, AstraZeneca, Basilea Pharma, Batxer, BioLineRX Ltd., Celgene SLU, Eisai, Ipsen Pharma, Incyte; Financial Interests, Personal, Other, Direct research fund: Servier, Merck, Sharp and Dhome, Novocure, QED Therapeutics Inc, Roche, Sanofi-Aventis, Zymeworks; Financial Interests, Personal, Invited Speaker: Lilly, Janssen; Financial Interests, Institutional, Research Grant: Amc Medical Research, Armo Biosciences, Basilea, Biokeralty Research Institute, Merck Sharp & Dohme, Oncomed Pharmaceuticals, QED Therapeutics, VCN Biosciences, AbbVie Farmaceútica, Ability Pharmaceuticals, Agios, Amgen, Aslan, AstraZeneca, Bayer, BeiGene, Biolinerx, Blueprint Medicines, Boston Biomedical, Bristol Myers Squibb (BMS), Cantargia, Celgene, Eisai, Erytech Pharma, F. Hoffmann-la Roche, Fibrogen, Genentech, Hallozyme, Immunomedics, Incyte, Ipsen, Lab. Menarini, Lilly, Loxo Oncology, Medimmune, Merimarck, Novocure, Millenim, Nelum, Novartis, Zymeworks, Pfizer, Pharmacyclics, Roche; Non-Financial Interests, Member: American Society of Clinical Oncology-ASCO, “Sociedad Española de Oncología Médica”–SEOM, Sociedad Europea de Oncología Médica-ESMO. R. Alvarez Gallego: Financial Interests, Institutional, Research Funding: Servier; Financial Interests, Institutional, Other, Travel, Accomodations, Expenses: Roche. E. Van Cutsem: Financial Interests, Personal, Advisory Board: AbbVie, ALX, Amgen, Array, Astellas, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, GSK, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Nordic, Pierre Fabre, Pfizer, Roche, Seattle Genetics, Servier, Takeda, Terumo, Taiho, Zymeworks; Financial Interests, Institutional, Research Grant: Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier. R.S. Conde: Financial Interests, Institutional, Other, Travel, Accomodations, Expenses: AstraZeneca. A. Hanauske: Financial Interests, Institutional, Stocks/Shares: Eli Lilly; Financial Interests, Institutional, Other, Honoraria: Ameos, Helios, SOTIO, Imaging Endpoints, Emergence Therapeutics, Yamaha, Apogenics, Ptc Therapeutics, Lilly Deutchland. J. Tabernero: Financial Interests, Personal, Advisory Board, scientific consultancy role: Orion Biotechnology, Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd., Genentech Inc., HalioDX SAS, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics, TheraMyc, Hutchinson MediPharma International, Scandion Oncology, Ona Therapeutics, SOTIO Biotech, Inspirna Inc., Scorpion Therapeutics, Tolremo Therapeutics; Financial Interests, Personal, Invited Speaker, educational collaboration: Medscape Education, Physicians Education Resource (PER), PeerView Institute for Medical Education, Imedex / HMP; Financial Interests, Personal, Invited Speaker, educacional collaboration: MJH Life Sciences; Financial Interests, Personal, Advisory Board: Cardiff Oncology; Financial Interests, Personal, Stocks/Shares: Oniria Therapeuics; Financial Interests, Institutional, Research Grant, ACRCelerate: Colorectal Cancer Stratified: Fundación Científica de la Asociación Española Contra el Cáncer; Financial Interests, Institutional, Research Grant, OPTIMISTICC: Opportunity to Investigate the Microbiome’s Impact on Science and Treatment In Colorectal Cancer: Cancer Research UK; Financial Interests, Institutional, Funding, Clinical Trials & Research: Amgen Inc., Array Biopharma Inc., AstraZeneca Pharmaceuticals LP, Bristol Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd., Genentech Inc., Janssen-Cilag International NV, Merck Health KGAA, Merck, Sharp & Dohme de España, SA, Novartis Farmacéutica SA, PharmaMar SA, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA, Inc., BeiGene, Boehringer Ingelheim, HalioDX SAS, Hutchinson Medipharma, MedImmune, Menarini, Merus N V, Pfizer, Mirati; Non-Financial Interests, Member of Board of Directors, Board of Directors: Cancer Core Europe, Spanish Association Against Cancer-AECC; Non-Financial Interests, Member of Board of Directors, General Assembly: Horizon Europe Cancer Mission; Non-Financial Interests, Leadership Role, External Scientific Committee: Institute for Health Research INCLIVA–Clinical Hospital of Valencia, IdiSNA –Universidad de Navarra; Non-Financial Interests, Leadership Role, Scientific Advisory Board: Spanish National Cancer Research Centre (CNIO); Non-Financial Interests, Advisory Role, International Scientific Evaluation Committee: Bosch Health Campus (BHC); Non-Financial Interests, Advisory Role, Review Board: National Decade Against Cancer (NCT)-German Consortium for Translational Cancer Research (DKTK); Non-Financial Interests, Advisory Role, Scientific Advisory Board: Karolinska Comprehensive Cancer Centre; Non-Financial Interests, Advisory Role, International Review Committee (IRC): Oncode Institute; Non-Financial Interests, Advisory Role, Scientific Advisory Board (SAB): Oslo University Hospital Comprehensive Cancer Centre (OUH CCC); Non-Financial Interests, Leadership Role, Governance Advisory Committee: European Organization for Research and Treatment of Cancer -EORTC; Non-Financial Interests, Leadership Role, Vice Chairman: World Innovative Networking (WIN) Consortium in Personalized Cancer Medicine; Non-Financial Interests, Other, Coordinating PI & Steering Committee Member. Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutical LP, Boehringer Ingelheim, MedImmune, Menarini, Merck Healthcare KGAA, Merck, Sharp & Dohme de España SA, Pfizer, Servier; Non-Financial Interests, Principal Investigator, Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutics LP, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd., Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, MedImmune, Menarini, Merck Healthcare KGAA, Merck, Sharp & Dohme de España SA, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc.; Non-Financial Interests, Other, Steering Committee Member. Clinical Trials & Research: Debiopharm International SA, F. Hoffmann-La Roche Ltd., Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, Merus NV, Taiho Pharma USA Inc.; Non-Financial Interests, Other, Coordinating PI. Clinical Trials & Research: Mirati; Non-Financial Interests, Member: AACR, ASCO, EACR, EORTC, SEOM; Other, President: Oncology Master Plan–Catalonia Department of Health; Other, Advisory Committee: Advisory Committee on Pharmaceutical Provision Financing under the Spanish National Health System. All other authors have declared no conflicts of interest.