Clinical Trial of SOT102 Antibody Drug Conjugate in Patients With Advanced Gastric and Pancreatic Adenocarcinoma (CLAUDIO-01)

Prior treatment

• Patients with hepatitis B will be eligible if: •there is serologic evidence of a resolved prior HBV infection (HBsAg-negative and anti-HBc–positive
• Major surgical intervention ≤28 days prior to ICF signature or incomplete wound healing after surgical intervention
• 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
• Time since last transfusion of RBCs ≤14 days before cycle 1 day 1
• Patient has been previously treated with the maximum cumulative dose of anthracyclines
• 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.
• Alcohol or drug abuse as determined by the investigator
• New York Heart Association class ≥2 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

Other illness

• Hypersensitivity or intolerance to any component of trial intervention
• Patients with hepatitis C will be eligible if: •they have completed curative antiviral treatment and have HCV viral load below the limit of quantification
• Severe preexisting medical conditions as per judgement of the investigator
• History of interstitial pneumonitis or pulmonary fibrosis
• Active infection requiring systemic therapy that is not clinically controlled before the signature of the ICF
• Psychiatric condition or social situation that, in the opinion of the investigator, preclude that the patient is able to comply with trial requirements
• History of major ventricular arrhythmias

Lab values

• Patients with HIV will be eligible if •CD4+ T-cell (CD4+) counts ≥350 cells/uL •they have no history of AIDS-defining opportunistic infections •they are not currently on HIV therapy
• History or family history of congenital long QT syndrome

Age

• Family history of sudden cardiac death before age 50

Other

• Patient has peripheral sensory neuropathy grade ≥2
• Bradycardia (<50 beats per minute)

• Age ≥18 years
• Part B- Adequate tumor tissue or cytology sample (FFPE blocks) or unstained slides from archival biopsy available or willingness to undergo a fresh tumor biopsy
• Part B- Patient has advanced inoperable or metastatic disease
• Written informed consent given prior to any trial-specific procedures
• Part B- Patient must have at least one measurable lesion according to RECIST 1.1
• Part B - Patients with gastric/GEJ adenocarcinoma (gastric B) - Histological or cytological evidence of adenocarcinoma of the stomach or GEJ that is advanced or metastatic
• Part B- Patients with gastric/GEJ adenocarcinoma (gastric B) - Must have HER2-negative tumors
• Part B- Patients with pancreatic adenocarcinoma (pancreatic B) Histological or cytological evidence of adenocarcinoma of the pancreas that is advanced or metastatic
• Part C- Adequate 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.
• Part C- Patient has advanced inoperable or metastatic disease
• Part C- Measurable disease according to RECIST 1.1.
• Patient is, in the judgement of the investigator, an appropriate candidate for experimental therapy
• Part C- Patients with gastric/GEJ adenocarcinoma (gastric C) - Must have received at least two prior systemic therapies for advanced or metastatic disease. If HER2 overexpression: must have received anti-HER2 therapy.
• Part C- Patients with pancreatic adenocarcinoma (pancreatic C) - Histological or cytological evidence of adenocarcinoma of the pancreas that is advanced or metastatic
• Adequate organ function as assessed by the following parameters: hematologic; hepatic; renal; prothrombin time/international normalized ratio (INR); albumin; proteinuria; Serum concentrations of potassium, magnesium, and calcium within normal range
• Part C- Patients with pancreatic adenocarcinoma (pancreatic C) - Must have received at least one prior systemic therapy for advanced or metastatic disease If HER2 overexpression: must have received anti-HER2 therapy.
• Part D- Adequate 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.
• Part D- Patient must have at least one measurable lesion according to RECIST 1.1. At least one measurable lesion must be outside of an earlier radiation field or must have progressed after radiation therapy
• Part D- Patients with gastric/GEJ adenocarcinoma (gastric D) - Histological or cytological evidence of adenocarcinoma of the stomach or GEJ that is advanced inoperable or metastatic
• Part D- Patients with gastric/GEJ adenocarcinoma (gastric D) - Must have HER2-negative tumors
• Part D- Patients with pancreatic adenocarcinoma (pancreatic D) - Histological or cytological evidence of adenocarcinoma of the pancreas that is advanced inoperable or metastatic
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• Patient agrees not to participate in other interventional clinical trials while enrolled in the present trial (with the exception of survival follow-up period)
• Estimated life expectancy ≥3 months as per investigator’s assessment
• A female patient is eligible to participate if she is not pregnant, not breastfeeding, and one of the following conditions applies: Not a woman of childbearing potential (WOCBP). A WOCBP is defined as fertile, following menarche and until becoming postmenopausal unless permanently sterile. A 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 SOT-102 or first-line SoC treatment (whichever occurs later)
• Male patients must agree to use a condom during treatment and for 9 months after SOT102 or first-line SoC treatment discontinuation. Male pat wishing to become a father during or after the trial should consider sperm preservation. WOCBP partner of male part should use highly effective contraception methods for 9 months after SOT102 or first-line SoC treat discontinuation.
• Left ventricular ejection fraction (LVEF) ≥50% as determined by echocardiography or nuclear medicine methodology (multiple gated acquisition scanning [MUGA])
• QTcF interval <450 msec on screening electrocardiogram (ECG)
• All previous cancer therapies for locally advanced gastric/pancreatic cancer and any agents that have not received regulatory approval for any indication must have been discontinued prior to day 1 of cycle 1 (Note: not applicable in France).
• Adequate tumor tissue from biopsy or fine needle aspiration (FNA) (formalin-fixed paraffin-embedded [FFPE] blocks), or unstained slides from archival biopsy available or willingness to undergo a fresh tumor biopsy.
• Part A- Patient has advanced inoperable or metastatic disease
• Part A- Patient has received and/or has been determined to be intolerant of all SoC therapy known to confer clinical benefit
• Part A- Measurable or non-measurable disease according to RECIST 1.1
• Part A- Histological or cytological evidence of adenocarcinoma of the pancreas that is advanced or metastatic