Gastric and pancreatic adenocarcinoma MedDRA version: 21.1 Level: LLT Classification code 10066354 Term: Adenocarcinoma of the gastroesophageal junction System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10051971 Term: Pancreatic adenocarcinoma System Organ Class: 100000004864
Conditions
Interventions
Product Name: SOT102
Product Code: SOT102
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: antibody-drug conjugate of an anti-CLDN18.2 mAb and the cytotoxic drug PNU159682, coupled by a
Sponsors
SOTIO Biotech a.s.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria applicable to all trial parts 1Age =18 years 2Written informed consent given prior to any trial-specific procedures 3Adequate organ function as assessed by the following parameters: hematologic; hepatic; renal; prothrombin time/international normalized ratio (INR); albumin; proteinuria. 4Eastern Cooperative Oncology Group (ECOG) performance status =1 5Estimated life expectancy =3 months as per investigator’s assessment 6A female patient is eligible to participate if she is not pregnant, not breastfeeding, and one of the following conditions applies: 6.1Not a woman of childbearing potential (WOCBP). A WOCBP is defined as fertile, following menarche and until becoming post-menopausal unless permanently sterile. 6.2A WOCBP who agrees to use a highly effective contraceptive method during the treatment period and for at least 9 months after the last dose of SOT102 7Male patients must agree to use a condom during treatment and for 9 months after SOT102 or first-line SoC treatment discontinuation 8Left ventricular ejection fraction (LVEF) =50% as determined by echocardiography or nuclear medicine methodology (multiple gated acquisition scanning [MUGA]) 9QTcF interval <450 msec on screening electrocardiogram (ECG) 10Patient is, in the judgement of the investigator, an appropriate candidate for experimental therapy 11Patient agrees not to participate in other interventional clinical trials while enrolled in the present trial (with the exception of survival follow-up period) PartA 12Adequate tumor tissue or cytology sample or unstained slides from archival biopsy available or willingness to undergo a fresh tumor biopsy 13All previous cancer therapies and any agents that have not received regulatory approval for any indication must have been discontinued 14Patient has advanced inoperable or metastatic disease 15Patient has no better treatment option available 16Measurable or non-measurable disease according to RECIST 1.1 17Histological or cytological evidence of adenocarcinoma of the stomach or GEJ or pancreas that is advanced or metastatic PartB 12Adequate tumor tissue or cytology sample (FFPE blocks) or unstained slides from archival biopsy available or willingness to undergo a fresh tumor biopsy 13Patient has advanced inoperable or metastatic disease 14Patient must have at least one measurable lesion according to RECIST 1.1 Patients with gastric/GEJ adenocarcinoma (gastric B) 15Histological or cytological evidence of adenocarcinoma of the stomach or GEJ that is advanced or metastatic 16Must have HER2-negative tumors Patients with pancreatic adenocarcinoma (pancreatic B) 15Histological or cytological evidence of adenocarcinoma of the pancreas that is advanced or metastatic PartC 12Adequate tumor tissue or cytology sample (FFPE blocks) or unstained slides from archival biopsy available or willingness to undergo a fresh tumor biopsy. Tumor sample must have CLDN18.2 expression using a central immunohistochemistry method. 13All previous cancer therapies and any agents that have not received regulatory approval for any indication must have been discontinued 14Patient has advanced inoperable or metastatic disease 15Measurable disease according to RECIST 1.1. Patients with gastric/GEJ adenocarcinoma (gastric C) 16Histological or cytological evidence of adenocarcinoma of the stomach or GEJ that is advanced or metastatic 17Must have received at least two prior systemic therapies for advanced or metastatic disease. Patients with
Exclusion criteria
Exclusion criteria: 1.Prior therapy with any agent directed at CLDN18.2 2.Patient has received radiation therapy =14 days before day 1 of cycle 1 or has not recovered to grade =1 from treatment-related side effects 3.Severe preexisting medical conditions as per judgement of the investigator 4.History of interstitial pneumonitis or pulmonary fibrosis 5.Symptomatic central nervous system malignancy. Patients with asymptomatic or treated central nervous system metastases may be eligible if they are not treated with corticosteroids or anticonvulsants and the disease is stable for at least 60 days. 6.Patient has peripheral sensory neuropathy grade =2 7.Active infection requiring systemic therapy within =7 days prior to day 1 of cycle 1 8.Known history of HIV infection or known active hepatitis B or hepatitis C 9.Alcohol or drug abuse as determined by the investigator 10.Psychiatric condition or social situation that, in the opinion of the investigator, preclude that the patient is able to comply with trial requirements 11.New York Heart Association class =3 heart failure, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, myocardial infarction, cerebrovascular accident or hypertensive crisis within 6 months prior to day 1 of cycle 1 12.History of major ventricular arrhythmias 13.History or family history of congenital long QT syndrome 14.Major surgical intervention =28 days prior to ICF signature or incomplete wound healing after surgical intervention 15.Hypersensitivity or intolerance to any component of trial intervention Part A Part B Part C and part D: 16.Any prior systemic therapy for metastatic cancer other than gastric or pancreatic cancer. Part B 17.Any prior systemic therapy for metastatic cancer other than gastric or pancreatic cancer. Patients with gastric/GEJ adenocarcinoma (gastric B) only: 18. Dihydropyrimidine dehydrogenase (DPD) deficiency 19. Patient has been treated with immunosuppressive medications =14 days prior to day 1 of cycle 1. Part D 17.Patients with contraindications to any component of the first-line SoC treatment Patients with gastric/GEJ adenocarcinoma (gastric D) only: 18.DPD deficiency 19.Patient has been treated with immunosuppressive medications =14 days prior to day 1 of cycle 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Part A-B :MTD is defined as the highest dose level tested below the dose level associated with =33% of dose-limiting toxicity (DLT)-evaluable patients experiencing a DLT. The RP2D will be selected based on integrated evaluation of the totality of clinical and preclinical data, for all dose levels tested. Part C (SOT102 monotherapy, cohort expansion) Objective response rate (ORR) Part D (SOT102 combined with first-line SoC treatment, cohort expansion) ORR;Timepoint(s) of evaluation of this end point: N/A;Main Objective: Part A and Part B To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of SOT102 given as monotherapy and in combination with first-line SoC treatment. MTD is defined as the highest dose level tested below the dose level associated with =33% of dose-limiting toxicity (DLT) evaluable patients experiencing a DLT. The RP2D will be selected based on integrated evaluation of the totality of clinical and preclinical data, for all dose levels tested. Part C and Part D To assess the efficacy of SOT102 in monotherapy and in combination with first-line SoC treatment by objective response rate;Secondary Objective: Part A and Part B To assess the safety and tolerability of SOT102 in monotherapy and in combination with first-line SoC treatment by the occurrence of DLTs, occurrence of treatment-emergent AEs (TEAEs), SOT102-related AEs, serious AEs, AEs leading to premature discontinuation of SOT102, deaths, or clinical laboratory test abnormalities. To characterize the pharmacokinetics (PK) of total SOT102, conjugated SOT102, main metabolites. Part C and Part D To evaluate additional measures of efficacy of SOT102 in monotherapy and in combination with first-line SoC treatment by duration of response, progression-free survival per RECIST 1.1, clinical benefit rate per RECIST 1.1 (Part C only), overall survival. To assess the safety and tolerability of SOT102 in monotherapy and in combination with first-line SoC t | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The occurrence of DLTs, occurrence of treatment-emergent AEs (TEAEs), SOT102- related AEs, serious AEs (SAEs), AEs leading to premature discontinuation of SOT102, deaths, or clinical laboratory test abnormalities • PK of total SOT102, conjugated SOT102, PNU-EDA-GGT (M4), PNU-EDA-GG (M5), and PNU-EDA-G (M6) • Anecdotal tumor response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by type and CLDN18.2 expression. The number of patients with detected antibodies against any part of SOT102 Additionally for PartC & Part D Assessment of global and disease-specific QoL by patient-reported questionnaires EORTC QLQ-C30 and EORTC QLQ-STO22 for patients with gastric cancer, and EORTC QLQC30 and EORTC QLQ-PAN26 for patients with pancreatic cancer Part D in additon: DoR and PFS per RECIST 1.1, OS;Timepoint(s) of evaluation of this end point: N/A | — |
Countries
Belgium, Czechia, France, Spain, United States
Contacts
Public ContactClinical Trial SOTIO
SOTIO Biotech a.s.
Outcome results
None listed