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 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.
• Willing to adhere to the prohibitions and restrictions specified in this protocol.
• Capable of giving signed informed consent (voluntarily), indicating that the patient understands the purpose and procedures required for the study and is willing to comply with the requirements and restrictions listed in the informed consent form and in this protocol.
• Patients aged ≥ 18 years at moment of signing informed consent form.
• Life expectancy of \> 12 weeks.
• ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1.
• BMI ≥ 18.0 and ≤ 35.0 kg/m2 and weight at least 50 kg and no more than 120 kg at screening.
• Overtly healthy based on medical history, physical findings, vital signs, ECG at the time of screening, as judged by the Investigator. Note: one retest of vital functions and ECG is allowed within the screening window.
• Adequate liver- and kidney function, defined by the following laboratory results obtained during screening visit:
‣ AST, ALT, and alkaline phosphatase ≤ 2.5x the upper limit of normal (ULN) as determined by the UMCG laboratory reference values.
⁃ Serum bilirubin ≤ 2.0x ULN as determined by the UMCG laboratory reference values. Patients with known Gilbert disease who have serum bilirubin level ≤ 3x ULN may be enrolled.
⁃ INR or APTT ≤ 1.5x ULN as determined by the UMCG laboratory reference values. This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
⁃ eGFR (based on plasma-creatinine) = \>30 mL/min.
⁃ Serum albumin \>35 g/L.
• No other clinically significant laboratory abnormalities as determined by the investigator. Note: one retest of lab tests is allowed within the screening window.
⁃ Female patients should be at least 1 year post-menopausal (amenorrhea \>12 months and/or follicle-stimulating hormone \>30 mIU/mL) at screening or surgically sterile (bilateral oophorectomy, hysterectomy, or tubal ligation).
⁃ Male subjects who are sexually active with a female partner of childbearing potential must agree to the use of an effective method of birth control, and must not donate sperm, until 3 months after administration of 89Zr-DFO-N-Suc-scFv (F8 or C9).
∙ Medical inclusion Criteria:
∙ Colon Carcinoma:
• Patients diagnosed with colon carcinoma stage I-IV, according to the 8th edition of the TNM-classification.
• Histologically confirmed diagnosis of colon carcinoma.
• Neo-adjuvant treatment according to the standard of care.
∙ Rectal Carcinoma:
• Patients diagnosed with rectal carcinoma stage I-IV, according to the 8th edition of the TNM-classification.
• Histologically confirmed diagnosis of rectal carcinoma.
• Neo-adjuvant treatment according to the standard of care.
∙ Osteosarcoma:
• Patients diagnosed with osteosarcoma stage I-IV, according to AJCC staging for Bone Sarcoma.
• Histologically confirmed diagnosis of osteosarcoma.
∙ 4\. Neo-adjuvant treatment according to the standard of care.
∙ Chondrosarcoma:
• Patients diagnosed with chondrosarcoma stage I-IV, according to AJCC staging for Bone Sarcoma.
• Histologically confirmed diagnosis of chondrosarcoma.
• Neo-adjuvant treatment according to the standard of care.
∙ Lung Carcinoma:
• Anticipated diagnosis of Non-Small Cell Lung Carcinoma (NSCLC) stage I-IV, according to the 8th edition of the TNM-classification, based on imaging modalities such as (PET)/CT or based on cytology.
• Neo-adjuvant treatment according to the standard of care.
∙ Head and Neck Squamous Cell carcinoma (HNSCC):
• Patients diagnosed with HNSCC of the oral cavity, oropharynx, nasal cavity, nasopharynx, hypopharynx and larynx.
• Histologically confirmed diagnosis of HNSCC.
• Neo-adjuvant treatment according to the standard of care.
∙ Oesophageal and gastric carcinoma:
• Patients diagnosed with oesophagus carcinoma stage I-IV according to the 7th edition of the TNM-classification.
• Patients diagnosed with gastric carcinoma stage I-IV according to the 7th edition of the TNM-classification.
• Histologically confirmed diagnosis of oesophageal- or gastric carcinoma.
• Neo-adjuvant treatment according to the standard of care.
∙ Pancreas carcinoma:
• Anticipated diagnosis of pancreas carcinoma stage I-IV according to the 8th edition of the TNM-classification, based on imaging modalities such as (PET)/CT or based on cytology.
• Histologically or cytologically confirmed diagnosis of pancreas carcinoma.
• Neo-adjuvant treatment according to the standard of care.
∙ Bladder carcinoma:
• Patients diagnosed with invasive bladder carcinoma stage I-IV according to the 7th edition of the TNM-classification.
• Histologically confirmed diagnosis of bladder carcinoma.
• Neo-adjuvant treatment according to the standard of care.
∙ Glioblastoma:
• Anticipated diagnosis of a high-grade glioma (glioblastoma, grade 4 according to the WHO classification) based on imaging modalities such as MRI and/or CT or a biopsy.
• Karnofsky performance status of at least 70%.
• Neo-adjuvant treatment according to the standard of care.