Clinical Trial of SOT102 Antibody Drug Conjugate in Patients With Advanced Gastric and Pancreatic Adenocarcinoma

A Multicentric Phase 1/2 Trial to Evaluate the Safety and Efficacy of SOT102 as Monotherapy and in Combination With Standard of Care Treatment in Patients With Gastric and Pancreatic Adenocarcinoma

This trial will assess the MTD and RP2D of SOT102 administered as monotherapy (Part A) and in combination with first-line SoC treatment (nab-paclitaxel/ gemcitabine; Part B) and efficacy of SOT102 administered as monotherapy (Part C) and in combination with first-line SoC treatment (Part D) in patients with advanced or metastatic pancreatic adenocarcinoma.

The trial will have the following parts:

• Part A: Dose escalation, first-in-human, single-agent phase 1 trial of SOT102 in advanced/metastatic pancreatic cancer patients with unmet medical need (CLDN18.2 agnostic)
• Part B : Phase 1b dose escalation combination trial of SOT102 in combination with nab-paclitaxel/gemcitabine as SoC regimen for first-line treatment of patients with advanced/metastatic pancreatic cancer (CLDN18.2 agnostic)

Once an RP2D in the respective phase 1 evaluation (Part A and Part B) has been identified, expansion parts (Part C and Part D) are planned:

• Part C : Single-agent SOT102 expansion at RP2D identified in Part A in pancreatic cancer after one or more prior systemic therapies (second+ line) for locally advanced or metastatic disease (CLDN18.2 positive)
• Part D : SOT102 in combination with nab- paclitaxel/gemcitabine for first-line treatment expansion at RP2D identified in Part B in pancreatic cancer (CLDN18.2 positive)

Inclusion Criteria:

All Parts (key criteria)

• Hematologic: Absolute neutrophil count ≥1.5×10⁹/L, platelets ≥100×10⁹/L, hemoglobin ≥9 g/dL
• Hepatic: Bilirubin ≤1.5× upper limits of normal (ULN), ALT and AST ≤2.5×ULN; in case of liver involvement: AST and ALT ≤5×ULN
• Renal: Creatinine clearance ≥60 mL/min calculated by Cockcroft-Gault formula
• Prothrombin time/international normalized ratio (INR) ≤1.5×ULN
• Albumin ≥3.0 mg/dL
• Proteinuria <1 g/24 hours
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• Estimated life expectancy ≥3 months as per investigator's assessment
• A female patient is eligible to participate if she is not pregnant, not breastfeeding, not of childbearing potential/ agreed with contraception

Part A

• Patient has advanced inoperable or metastatic disease
• Patient has no better treatment option available
• Measurable or non-measurable disease according to RECIST 1.1
• Histological or cytological evidence of adenocarcinoma of pancreas that is advanced or metastatic

Part B (in addition to relevant A criteria)*Histological or cytological evidence of adenocarcinoma of the pancreas that is advanced or metastatic (pancreas)

Part C (in addition to relevant A criteria)*Must have received at least one prior systemic therapy for advanced or metastatic disease (pancreas)

Part D (in addition to relevant B criteria)*Histological or cytological evidence of adenocarcinoma of the pancreas that is advanced inoperable or metastatic (pancreas)

Exclusion Criteria:

All Parts (key criteria)

• 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
• Severe preexisting medical conditions as per judgement of the investigator (e.g., active gastric or GEJ ulcer with or without bleeding, complete or incomplete gastric outlet syndrome with persistent or repetitive bleeding)
• History of interstitial pneumonitis or pulmonary fibrosis
• 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.
• Patient has peripheral sensory neuropathy grade ≥2
• Active infection requiring systemic therapy within ≤7 days prior to day 1 of cycle 1
• History of major ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, Torsades de Pointes)
• Bradycardia (<50 beats per minute)
• Family history of sudden cardiac death before age 50
• History or family history of congenital long QT syndrome
• Major surgical intervention ≤28 days prior to ICF signature or incomplete wound healing after surgical intervention
• Time since last transfusion of RBCs ≤14 days before cycle 1 day 1
• Vaccination with a live or live-attenuated vaccine within 30 days prior the first dose of trial interventions

Part B/D (key)

*Patients with contraindications to any component of the first-line SoC treatment