The Safety, Tolerability and Biodistribution of a Single Intravenous Administration of Two Zirconium-89 Labelled Vartumabs (F8scFV or C9scFv) in Patients With Solid Tumors - a Phase 0, Open Label, PET/CT Molecular Imaging Basket Trial (VARTUTRACE)

NCT06645808 EARLY_PHASE1 RECRUITING

VARTUTRACE is a first-in-human PET/CT molecular imaging study in patients with solid tumors. This study will investigate the biodistribution and pharmacology of two antibody fragments binding oncofetal Chondroitin Sulfate (CS). Oncofetal CS are tumor-specific carbohydrate motifs present in proteoglycans and identified by VAR2 Pharmaceuticals as expressed during fetal development. Oncofetal CS reappears in the vast majority of cancers while remaining largely absent from normal tissues. VAR2 Pharmaceuticals recently developed antibodies specific for oncofetal CS. VARTUTRACE uses two of these as radiolabeled antibody fragments to study biodistribution, tumor accumulation, pharmacodynamics and clearance pathways in a diverse patient population.

Details

Lead sponsor	Var2 Pharmaceuticals
Phase	EARLY_PHASE1
Status	RECRUITING
Enrolment	32
Start date	2024-12-10
Completion	2026-09

Conditions

• Solid Tumor
• Colon Carcinoma
• Rectal Carcinoma
• Osteosarcoma
• Chondrosarcoma
• Lung Carcinoma
• Head and Neck Squamous Cell Carcinoma
• Esophageal Carcinoma
• Gastric Carcinoma
• Pancreas Carcinoma

Interventions

• 89Zr-DFO-N-Suc-F8scFv
• 89Zr-DFO-N-Suc-C9scFv
• PET/CT scan

Primary outcomes

• Biodistribution and pharmacokinetics of the radiolabeled IMP — Day 1, 2, and 4 after dosing
  Biodistribution and pharmacokinetics of the IMP are defined by the amount of IMP that is taken up per target organ or tissue over time. The radioactive dose absorbed per target organ or tissue over time is determined using whole-body PET/CT imaging at various time points post-injection. In addition, blood samples will be taken at various time points post-injection to determine IMP plasma level concentrations. The ICRP 89 values will be used to calculate the effective dose in each organ. Descriptive statistics of absorbed doses to target organs and tissues specified will be tabulated. The blood concentrations will be presented using descriptive summary statistics.
• Tumor-specific uptake of the IMP — Day 1 - 7 after dosing
  Tumor-specific uptake of the IMP is defined as the amount of IMP that tumors uptake compared to normal tissue. Tumor-specific uptake of the IMP is captured using PET/CT imaging and quantified by calculating the tumor-to-background ratio (TBR), which is determined by the ratio of radioactivity taken up by the tumor and radioactivity taken up by healthy reference tissue. A qualified PET investigator will obtain the raw data. PET/CT-derived TBR will be quantified for each patient and compared to standard of care imaging techniques. Variables will be presented as qualitative data. Data interpretation is considered descriptive.
• Incidence of treatment emergent adverse events (AE) (safety and tolerability) — Study duration (up to 56 days)
  Safety and tolerability will be assessed by the number of participants with treatment-emergent AEs, with abnormal laboratory tests results (including the occurrence of anti-drug antibodies), abnormal vital signs, abnormal ECG readings, and abnormal physical examination findings from the time of i.v. administration of the IMP until the end of the follow-up period. For this objective, variables will be presented as qualitative data. Interpretations of this data will be descriptive

Countries

Netherlands