Clinical trial NCT06617169: Dose-Escalation of MNPR-101-PCTA-177Lu in Solid Tumors
Official title: Open Label, Phase 1a, Dose-Escalation Study Evaluating the Safety of Fractionated MNPR-101-PCTA-177Lu Dosing in the Treatment of Solid Tumor Cancers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumor, Adult
Bladder Cancer
Urothelial Carcinoma
Triple-negative Breast Cancer
Lung Cancer
Colorectal Cancer
Gastric Cancer
Ovarian Cancer
Pancreatic Cancer
Lead sponsor: Monopar Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-09-27
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Detailed description: This Phase 1a study will enroll qualified participants from the MNPR-101-D001 imaging study. Patients will receive three equal doses of MNPR-101-PCTA-177Lu, dose-escalating in cohorts of two starting at Dose Level 1 (960 MBq).On Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1, patients will receive a 20-minute intravenous infusion of MNPR-101-PCTA-177Lu consisting of an antibody with radioactivity ranging from 480-2240 MBq (Dose Levels 0-4).

This study employs a Time-to-Event Bayesian Optimal Interval Design (TITE-BOIN). Dosing of subsequent cohorts will escalate, stay, or de-escalate based on TITE-BOIN predetermined, fixed dose escalation / de-escalation rules.

Any hematologic event must be ≤ Grade 1 for dosing to occur, i.e., patients with an active ≥ Grade 2 hematologic event may not be dosed. Any patient experiencing a ≥ Grade 2 allergic reaction during or immediately following infusion will not receive further treatment. Patients experiencing a DLT, at least possibly related to MNPR-101-PCTA-177Lu and occurring within 6 weeks of C1D1, will not receive any further doses. C1D15 and C2D1 doses may be delayed for up to 14 days for specified adverse events.

All subjects will undergo SPECT imaging on Cycle 1 Day 8 and Cycle 2 Day 8. CT scans will occur on Cycle 1 Day 43, Cycle 2 Day 1, and Cycle 2 Day 43; a baseline CT scan must be provided. These will allow for the assessment of tumor SUVs, as well as the radiologic response rate by RECIST 1.1.

Patients will be followed for safety for 12 weeks following the last dose of MNPR-101-PCTA-177Lu.

Eligibility criteria: Inclusion Criteria:

1. Participated in the MNPR-101-D001 study.
2. 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.
3. 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.
4. 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.

Exclusion Criteria:

1. Chemotherapy, radiotherapy (other than short cycle of palliative radiotherapy), or immunotherapy within 14 days prior to administration of MNPR-101-PCTA-177Lu.
2. Continuing ≥ Grade 3 adverse reactions from prior systemic therapy (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0).
3. 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.
4. 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 \[https://www.kidney.org/professionals/kdoqi/gfr_calculator\].
5. Safety event of significance in MNPR-101-D001 study:

   1. a related CTCAE Grade 4 hematologic or hepatologic event
   2. a related CTCAE Grade 3 hematologic or hepatologic event which lasted \>30 days
6. 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.
7. 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.
8. Cognitive impairment or contraindications that may compromise ability to give informed consent or comply with requirements of the study.

Primary outcomes:
measure: Identify the dose-limiting toxicities (DLTs) of fractionated MNPR-101-PCTA-177Lu dosing and their frequency
timeFrame: For 6 weeks after the first dose
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of fractionated MNPR-101-PCTA-177Lu dosing
timeFrame: From dosing to the End of Study at 24 weeks
Secondary outcomes:
measure: Assessment radiologic response rate by RECIST 1.1
timeFrame: Every 6 weeks after initial dose
measure: Assessment of radiologic response rate by PERCIST 1.0
timeFrame: At 12 weeks after first dose (End of Cycle 1) and at 12 weeks after final dose (Safety Visit)
measure: Assess Radioactivity in whole blood and plasma following each fractionated MNPR-101-PCTA-177Lu dose
timeFrame: for 2 weeks after each dose
measure: To determine the maximum administered dose (MAD) for fractionated MNPR-101-PCTA-177Lu dosing
timeFrame: 6 weeks after the first dose
Other outcomes:
Locations:
city: North Melbourne
country: Australia
facility: Melbourne Theranostic Innovation Centre (MTIC)
state: Victoria
Study officials:
References: