Diagnostic Efficacy and Dosimetry of MNPR-101-DFO*-89Zr in Patients With Solid Tumors

Open Label Pilot Study Evaluating Diagnostic Efficacy and Dosimetry of MNPR-101-DFO*-89Zr in Patients With Solid Tumors

This is an open-label pilot study of a new PET/CT imaging agent MNPR-101-DFO*-89Zr in patients with solid tumor cancers. These cancers may include bladder/urothelial, triple-negative breast, lung, colorectal, gastric, ovarian, and pancreatic cancers.

MNPR-101-DFO*-89Zr is made of MNPR-101, a humanized IgG1 monoclonal antibody and a radioisotope Zirconium-89. This imaging agent may show where tumors are present in the body using a PET-scan.

Participants will be injected with the radioactive tracer once. After injection, participants will have 3 PET-scans. Each PET-scan will take about 30 minutes. The PET-scans are on separate days within 10 days after injection (e.g., 2 hours after injection, plus 3-5 days and 7-10 days after injection). Furthermore, the investigators will take blood samples 6 times (5 mL each). Blood pharmacokinetics (PK) will be measured on Day 1 at 10 min, 1h, 2h, once on Days 3-5, and once on Days 7-10.

The study will see if the new imaging agent correctly shows all tumors. In the future, this method may be useful to help predict who will benefit from certain therapies.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Colorectal Cancer; Pancreatic Cancer; Ovarian Cancer; Lung Cancer; Bladder Cancer; Urothelial Carcinoma; Triple-negative Breast Cancer; Solid Tumor, Adult
• Intervention / Treatment: Drug: MNPR-101-DFO*-89Zr; Diagnostic test: PET/CT Diagnostic Imaging

Detailed Description

This is an open-label, multi-center, imaging, and dosimetry pilot study to evaluate MNPR-101-DFO*-89Zr, a radiolabeled tracer composed of humanized IgG1 monoclonal antibody MNPR-101 which targets cancers that express the urokinase plasminogen activator receptor (uPAR) used with Positron Emission Tomography/Computed Tomography (PET/CT) imaging in patients with solid tumor cancers.

The study aims to determine the dosimetry and biodistribution, tumor standard uptake values (SUV), safety profile, and blood pharmacokinetics (PK) of MNPR-101-DFO*-89Zr.

On Day 1, patients will receive a single infusion of MNPR-101-DFO*-89Zr. All subjects will receive 37 to 74 MBq (1-2 mCi) of 89Zr with radioactivity determined based upon the site's PET/CT equipment. The antibody mass dose of MNPR-101-DFO*-89Zr will be increased in a stepwise fashion to a maximum of 80 mg. Before increasing to the next mass antibody dose level, each cohort of 2 patients will be assessed following the Day 7-10 visit for related hematologic or hepatologic events reported as CTCAE Grade 4, or CTCAE Grade 3 if lasting longer than 30 days.

PET/CT imaging will occur post-infusion at 2 h (Day 1), once on Days 3-5, and once on Days 7-10. PK blood sampling, for analysis via well or gamma counter, will occur post-infusion on Day 1 at 10 min, 1h, 2h, once on Days 3-5, and once on Days 7-10.

Dosimetry will be calculated using OLINDA/EXM or a similar software. Tumor SUVs will be assessed and compared to a prior 18F-FDG PET scan. PK measurements will be made via well or gamma counter and adjusted for radioactive decay.

The primary endpoints will assess dosimetry, biodistribution including target safety organs (e.g., liver, kidney, bone marrow, and lungs), tumor SUV, and the safety profile of MNPR-101-DFO*-89Zr. Patients will be followed for 1-month post infusion.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Director Clinical Operations; Phone Number: 847-794-8435; Email: monitoring@monopartx.com

Study Locations

• Australia
  • Victoria
    • North Melbourne, Victoria, Australia, 3051
      • Recruiting
      • Melbourne Theranostic Innovation Centre (MTIC)
      • Contact: Referral Coordinator; Phone Number: 03 9454 5800

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically and/or cytologically confirmed solid tumor cancer.
2. Age ≥18 years.
3. Measurable disease ≥ 1 cm on prior 18F-FDG PET/CT scan. Up to 4 subjects may be enrolled with FDG-avid disease which do not meet ≥ 1 cm measurement on CT.
4. Ability to understand and willingness to sign a written informed consent document.
5. A prior standard-of-care 18F-FDG PET/CT scan within past 60 days.
6. Tumor sample available for IHC testing to demonstrate uPAR expression.
7. Females of childbearing potential must have a negative serum pregnancy test at time of screening and a negative urine pregnancy test on Day 1 prior to study drug administration if screening is >7 days prior to Day 1. A rapid serum pregnancy test result performed as standard-of-care will be accepted if available.
8. Both males and females must agree to use highly effective contraceptive precautions if conception is possible during the dosing period and up to 1 month after dosing.
9. Female patients who are lactating must agree to discontinue breastfeeding prior to the dose of study drug and must refrain from breastfeeding for 1 month following the last dose of study drug.

Exclusion Criteria:

1. Chemotherapy, radiotherapy (other than short cycle of palliative radiotherapy), or immunotherapy within 14 days prior to administration of MNPR-101-DFO*-89Zr, or continuing adverse effects (>grade 1, excluding alopecia, anorexia, fatigue, and neuropathy) from such therapy (Common Terminology Criteria for Adverse Events [CTCAE] version 5.0).
2. Prior treatment with any radiopharmaceutical or investigational agents within 4 weeks or 5 effective half-lives, whichever is longer, prior to administration of the first dose of MNPR-101-DFO*-89Zr.

3. Have evidence of impaired organ function at Screening and within 1 week prior to dosing MNPR-101-DFO*-89Zr, particularly:

   • Bone marrow i. Platelets <75 K/mcL. ii. ANC <1.0 K/mcL.
   • Liver function i. AST/ALT >2.5xULN (institutional upper limits of normal) OR >5×ULN for patients with liver metastases.

   ii. Bilirubin >1.5xULN OR >3×ULN for patients with known Gilbert's Syndrome.

   • Renal function i. eGFR ≤45 mL/min determined using BSA-adjusted Chronic Kidney Disease Epidemiology Collaboration CKD-EPI 2021 formula [https://www.kidney.org/professionals/kdoqi/gfr_calculator].
4. Other serious, non-malignant diseases that may interfere (e.g., renal, hepatic, or hematologic) with the objectives of the study, safety, or compliance, as judged by the investigator.
5. Cognitive impairment or contraindications that may compromise the ability to give informed consent or comply with the requirements of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MNPR-101-DFO*-89Zr Single Infusion and PET/CT Imaging; Participants receive a single injection of MNPR-101-DFO*-89Zr on Day 1 with administered activity between 37-74 MBq (or 1-2 mCi). PET/CT imaging will occur post-infusion at 2 h (Day 1), once on Days 3-5, and once on Days 7-10.	Drug: MNPR-101-DFO*-89Zr; Participants will receive one dose of MNPR-101-DFO*-89Zr infused intravenously on Day 1 for PET scans; Diagnostic test: PET/CT Diagnostic Imaging; PET/CT imaging will occur post-infusion at 2 h (Day 1), once on Days 3-5, and once on Days 7-10 for tumor lesion observation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess dosimetry and biodistribution of MNPR-101-DFO*-89Zr	The biodistribution of MNPR-101-DFO*-89Zr is assessed via PET/CT imaging scans, particularly of target safety organs (e.g., liver, kidney, red marrow, and lungs). Dosimetry is calculated using OLINDA/EXM or a similar software.	Post infusion at 2 h on Day 1, once on Days 3-5, and once on Days 7-10.
To assess tumor Standard Uptake Value (SUV) of MNPR-101-DFO*-89Zr	Tumor SUV is measured via PET/CT imaging by calculating the amount of radiotracer uptake in identified tumors. SUV mean, max, and peak of the tumors will be summarized at each timepoint per subject. Tumor SUV will be analyzed between subjects with the same cancer type as well as between cancer types.	Post infusion at 2 h on Day 1, once on Days 3-5, and once on Days 7-10.
To assess safety of MNPR-101-DFO*-89Zr as assessed by CTCAE 5.0	The safety profile of MNPR-101-DFO*-89Zr will be determined through assessment of adverse event (AE) type, incidence, severity, time of appearance, and related causes (detected by physical explorations and laboratory tests). Adverse events will be graded and tabulated using NCI CTCAE v5.0.	Screening through Day 30 Safety Visit.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess pharmacokinetics (PK) of MNPR-101-DFO*-89Zr via well or gamma counter	PK, mean and standard deviation plasma drug concentration are collected and measured via well or gamma counter to assess the imaging agent's interaction in blood and/or serum at each timepoint per subject.	Post infusion at 10 min, 1 h and 2 h on Day 1, once on Days 3-5, and once on Days 7-10.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess tumor uptake to background and tumor uptake to liver ratios	Tumor to background (skeletal muscle) and tumor to liver uptake ratios using PET/CT imaging will be calculated from the lesion-free volume of interest (VOI) (reference tissue) using SUV_mean_lesion / SUV_mean_reference.	Post infusion at 2 h on Day 1, once on Days 3-5, and once on Days 7-10.
To assess benefit of added cold MNPR-101 antibody	Determination of optimal cold antibody will be assessed based on the level of cold antibody where PK values in blood plateau and behave approximately linearly on a log scale over time, using time-corrected gamma counts of whole blood and/or serum.	Post infusion at 10 min, 1 h and 2 h on Day 1, once on Days 3-5, and once on Days 7-10.

Collaborators and Investigators

• Sponsor: Monopar Therapeutics
• Investigators: Principal Investigator: Prof. Rod Hicks, MD, Melbourne Theranostic Innovation Centre (MTIC)

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2024
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: March 22, 2024
• First Submitted That Met QC Criteria: March 28, 2024
• First Posted (Actual): March 29, 2024

Study Record Updates

• Last Update Posted (Actual): May 22, 2025
• Last Update Submitted That Met QC Criteria: May 19, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms
• Other Study ID Numbers: MNPR-101-D001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes