PET-imaging of Two Vartumabs in Patients With Solid Tumors

NCT06645808 | Recruiting Early Phase 1

• 2 other identifiers: VAR2-2024-CS012024-513827-18-00
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Solid Tumor; Colon Carcinoma; Rectal Carcinoma; Osteosarcoma; Chondrosarcoma; Lung Carcinoma; Esophageal Carcinoma; Gastric Carcinoma; Pancreas Carcinoma; Bladder Carcinoma; Glioblastoma; Soft Tissue Sarcoma (STS); Breast Cancer; Head and Neck Squamous Cell Carcinoma

Keywords

Basket-trial; Oncology; Solid tumors

Outcome Measures

Primary Outcomes (3)

• Biodistribution and pharmacokinetics of the radiolabeled IMP

  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.

  Day 1, 2, and 4 after dosing

• Tumor-specific uptake of the IMP

  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.

  Day 1 - 7 after dosing

• Incidence of treatment emergent adverse events (AE) (safety and tolerability)

  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

  Study duration (up to 56 days)

Secondary Outcomes (1)

• Tumor-specific uptake of the IMP per cancer type

  Day 1 -7 after dosing

Other Outcomes (1)

• Presence of IMP and target in patient-derived tumor tissue

  Day 1 - 7 after dosing

Study Arms (2)

89Zr-F8scFv

EXPERIMENTAL

The first 3 patients of this arm will receive a single i.v. microdose (1 mg) administration of 89Zr-F8scFv 15 MBq, followed by three whole-body PET/CT scans on day 1, 2 and 4. After the first three patients, an interim analysis will be conducted to determine the optimal scanning time point and radiation dose. The following 13 patients will receive a single i.v. microdose administration of 89Zr-F8scFv between 15 - 30 MBq, followed by one whole-body PET/CT scan on the optimal scanning day (day 1-7). Each subject will have a follow-up visit approximately 28 days after IMP administration.

Biological: 89Zr-DFO-N-Suc-F8scFv; Radiation: PET/CT scan

89Zr-C9scFv

EXPERIMENTAL

The first 3 patients of this arm will receive a single i.v. microdose (1 mg) administration of 89Zr-C9scFv 15 MBq, followed by three whole-body PET/CT scans on day 1, 2 and 4. After the first three patients, an interim analysis will be conducted to determine the optimal scanning time point and radiation dose. The following 13 patients will receive a single i.v. microdose administration of 89Zr-C9scFv between 15 - 30 MBq, followed by one whole-body PET/CT scan on the optimal scanning day (day 1-7). Each subject will have a follow-up visit approximately 28 days after IMP administration.

Biological: 89Zr-DFO-N-Suc-C9scFv; Radiation: PET/CT scan

Interventions

89Zr-DFO-N-Suc-F8scFv BIOLOGICAL

89-Zirconium labeled short-chain variable fragment F8 targeting oncofetal CS.

89Zr-F8scFv

89Zr-DFO-N-Suc-C9scFv BIOLOGICAL

89-Zirconium labeled short-chain variable fragment C9 targeting oncofetal CS.

89Zr-C9scFv

PET/CT scan RADIATION

IMP administration will be followed by PET/CT scans on day 1, 2 and 4.

89Zr-C9scFv; 89Zr-F8scFv

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• Behavioral or cognitive impairment or psychiatric disease that, in the investigator's opinion, affects the patient's ability to understand and cooperate with the study protocol.
• Insufficient venous access for the study procedures.
• Close affiliation with the investigator, e.g. a close relative of the investigator, dependent person (e.g. employee or student), employee of the department of surgery or nuclear department of the UMCG,TRACER or affiliates.
• Any finding in the medical examinations or medical history giving, in the opinion of the investigator, reasonable suspicion of a disease or condition that makes treatment with the investigational drug unadvisable, or that might affect interpretation of the results of the study or render the patient at high risk for treatment complications.
• Participation in an interventional clinical study within 30 days prior to tracer administration that involved treatment with any drug (excluding vitamins and minerals) or medical device.
• The existence of a second concomitant active malignancy or treatment for a second malignancy within 1 year prior to IMP-administration that is not a solid tumor indication included in the VARTUTRACE study, except for localized basal or squamous cell cancer that has been cured at least 90 days before screening.
• Cardiac impairment with an estimated LVEF \<35 % Prolonged QTcF (\>450 ms), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG at the time of screening, as judged by the investigator.
• Any abnormalities in the vital signs of the patient, as judged by the investigator, as a result of which the patient cannot participate. Note: One retest of vital functions is allowed within the screening window.
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
• Major surgical procedure other than for the included diagnosis within four weeks before IMP administration. Disease-related procedures, e.g. the placement of a port-a-cath, placement of a drain, ERCP, are allowed.
• Current evidence or history of bacterial, viral or fungal infections within 7 days before 89Zr-DFON-Suc-scFv (F8 or C9) administration as judged by the Investigator.
• T \> 38.0°C or lab confirmed viral/bacterial/fungal infection (PCR) or symptoms suggestive of an infection)
• Received oral or IV antibiotics within \<7 days before administration.
• Any planned major surgery within the duration of the study (until follow-up visit) that is not related to the tumor, with the exception of any emergency surgeries.
• Prior allogeneic bone marrow transplantation or solid organ transplant.

Sponsors & Collaborators

• Var2 Pharmaceuticals: lead
• TRACER Europe BV: collaborator

Study Sites (1)

University Medical Center Groningen (UMCG)

Groningen, Provincie Groningen, 9713GZ, Netherlands

RECRUITING

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms; Osteosarcoma; Chondrosarcoma; Lung Neoplasms; Squamous Cell Carcinoma of Head and Neck; Esophageal Neoplasms; Stomach Neoplasms; Pancreatic Neoplasms; Urinary Bladder Neoplasms; Glioblastoma; Sarcoma; Breast Neoplasms; Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Esophageal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Gooitzen van Dam, MD, PhD

  TRACER Europe B.V.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne-Fleur Verhaar, MD

CONTACT

0031622989025; anne-fleur@tracercro.com

Noortje van Dijk, Msc

CONTACT

noortje@tracercro.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Initially, three patients per compound (89Zr-C9scFv and 89Zr-F8scFv) will be included according to alternating inclusion or patient availability (n=6). Subsequently, an interim analysis will be conducted to determine the optimal radiation dose and optimal scanning day for each radiolabeled antibody fragment. After the interim analysis, cohorts will be expanded with additional solid tumor indications and will include 13 more subjects per compound (n=26), resulting in 32 subjects overall. This basket trial aims to include at least one patient per indication. For expansion cohort subjects, IMP-administration will occur on day 1, with one PET/CT scan performed on the most optimal day (this was determined to be day 4). Optionally, patients can receive an additional day 6 scan to gain more insight into tumor retention.

Study Record Dates

• First Submitted: August 28, 2024
• First Posted: October 17, 2024
• Study Start: December 10, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: December 29, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)