Dose-Escalation of MNPR-101-PCTA-177Lu in Solid Tumors

NCT06617169 | Recruiting Phase 1 FDA Drug

• 1 other identifier: MNPR101-Lu-1-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, uncontrolled, multi-center, phase 1a MNPR-101-PCTA-177Lu dose-escalation study in patients with solid tumor cancers. Patients must have participated in the imaging study MNPR-101-D001 (actively recruiting, diagnostic study of MNPR-101-DFO\*-89Zr).

• TITE-BOIN will be used to objectively determine dose increase, no dose change, or dose decrease for each group of two patients.
• The treatment period consists of two 12-week cycles. Patients will receive three equal fractions of MNPR-101-PCTA-177Lu with radioactivity ranging from 480-2240 MBq on each of Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (12 weeks after Cycle 1 Day 1).
• Patients will be followed for 12 weeks after their last dose of MNPR-101-PCTA-177Lu.
• Patients will be imaged at specific timepoints during the study.

Conditions

Solid Tumor, Adult; Bladder Cancer; Urothelial Carcinoma; Triple-negative Breast Cancer; Lung Cancer; Colorectal Cancer; Gastric Cancer; Ovarian Cancer; Pancreatic Cancer

Outcome Measures

Primary Outcomes (2)

• Identify the dose-limiting toxicities (DLTs) of fractionated MNPR-101-PCTA-177Lu dosing and their frequency

  Dose-limiting toxicities (DLT) are at least possibly related to MNPR-101-PCTA-177Lu and occur within 6 weeks of C1D1. Participants experiencing a DLT will not receive any further doses. Participants will continue study participation through the 12-week post final dose Safety Visit.

  For 6 weeks after the first dose

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of fractionated MNPR-101-PCTA-177Lu dosing

  The safety profile of MNPR-101-PCTA-177Lu 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.

  From dosing to the End of Study at 24 weeks

Secondary Outcomes (4)

• Assessment radiologic response rate by RECIST 1.1

  Every 6 weeks after initial dose

• Assessment of radiologic response rate by PERCIST 1.0

  At 12 weeks after first dose (End of Cycle 1) and at 12 weeks after final dose (Safety Visit)

• Assess Radioactivity in whole blood and plasma following each fractionated MNPR-101-PCTA-177Lu dose

  for 2 weeks after each dose

• To determine the maximum administered dose (MAD) for fractionated MNPR-101-PCTA-177Lu dosing

  6 weeks after the first dose

Study Arms (5)

Level 0 - MNPR-101-PCTA-177Lu 480 MBq

EXPERIMENTAL

Drug: MNPR-101-PCTA-177Lu

Level 1 - MNPR-101-PCTA-177Lu 960 MBq

EXPERIMENTAL

Drug: MNPR-101-PCTA-177Lu

Level 2 - MNPR-101-PCTA-177Lu 1440 MBq

EXPERIMENTAL

Drug: MNPR-101-PCTA-177Lu

Level 3 - MNPR-101-PCTA-177Lu 1920 MBq

EXPERIMENTAL

Drug: MNPR-101-PCTA-177Lu

Level 4 - MNPR-101-PCTA-177Lu 2240 MBq

EXPERIMENTAL

Drug: MNPR-101-PCTA-177Lu

Interventions

MNPR-101-PCTA-177Lu DRUG

MNPR-101-PCTA-177Lu administered intravenously over approximately 20 minutes, followed by a normal saline flush. Dosing will occur on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1.

Level 0 - MNPR-101-PCTA-177Lu 480 MBq; Level 1 - MNPR-101-PCTA-177Lu 960 MBq; Level 2 - MNPR-101-PCTA-177Lu 1440 MBq; Level 3 - MNPR-101-PCTA-177Lu 1920 MBq; Level 4 - MNPR-101-PCTA-177Lu 2240 MBq

Eligibility Criteria

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

You may qualify if:

• Participated in the MNPR-101-D001 study.
• 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.
• Both males and females must agree to use highly effective contraceptive precautions if conception is possible during the dosing period and up to 3 months after dosing.
• Female patients who are lactating must agree to discontinue breastfeeding prior to the dose of study drug and must refrain from breastfeeding for 3 months following the last dose of study drug.

You may not qualify if:

• Chemotherapy, radiotherapy (other than short cycle of palliative radiotherapy), or immunotherapy within 14 days prior to administration of MNPR-101-PCTA-177Lu.
• Continuing ≥ Grade 3 adverse reactions from prior systemic therapy (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0).
• Prior treatment with any radiopharmaceutical or investigational agents within 4 weeks or 5 half-lives, whichever is longer, prior to administration of the first dose of MNPR-101-PCTA-177Lu other than MNPR-101-DFO\*-89Zr.
• Have evidence of impaired organ function at Screening and prior to dosing, particularly:
• Bone marrow: i. Platelets ≤150×10\^9/L. ii. Absolute neutrophil count ≤1.5×10\^9/L. iii. Hemoglobin \<9g/dL (no red blood cell transfusion in the previous 4 weeks).
• Liver function: i. AST/ALT \>3xULN (institutional upper limits of normal) OR \>5×ULN for patients with liver metastases.
• ii. Bilirubin \>1.5xULN OR \>3xULN 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 \[https://www.kidney.org/professionals/kdoqi/gfr\_calculator\].
• Safety event of significance in MNPR-101-D001 study:
• a related CTCAE Grade 4 hematologic or hepatologic event
• a related CTCAE Grade 3 hematologic or hepatologic event which lasted \>30 days
• Unacceptable value for projected organ dose based upon dosimetry from the MNPR-101-D001 study that exceeds safe absorbed dose limits, as determined by Monopar.
• Other serious, non-malignant diseases (e.g., renal, hepatic, or hematologic) that may interfere with objectives of the study, safety, or compliance, as judged by the investigator.
• Cognitive impairment or contraindications that may compromise ability to give informed consent or comply with requirements of the study.

Sponsors & Collaborators

• Monopar Therapeutics: lead

Study Sites (1)

Melbourne Theranostic Innovation Centre (MTIC)

North Melbourne, Victoria, 3051, Australia

RECRUITING

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Triple Negative Breast Neoplasms; Lung Neoplasms; Colorectal Neoplasms; Stomach Neoplasms; Ovarian Neoplasms; Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Pancreatic Diseases

Central Study Contacts

Director Clinical Operations

CONTACT

847-794-8435; monitoring@monopartx.com

Study Design

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

Model Details: Participants will be dosed in cohorts of two, starting at Dose Level 1. TITE-BOIN evaluates the number of participants that have been dosed at a given dose level and their outcomes and determines if the next cohort should stay at the same dose, increase dose, or decrease dose using a predetermined rule.

Study Record Dates

• First Submitted: September 18, 2024
• First Posted: September 27, 2024
• Study Start: October 8, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: May 21, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)