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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
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.
Melbourne Theranostic Innovation Centre (MTIC)
North Melbourne, Victoria, Australia
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.
Time frame: 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.
Time frame: From dosing to the End of Study at 24 weeks
Assessment radiologic response rate by RECIST 1.1
Radiologic response rate will be determined by RECIST 1.1 via CT scans every 6 weeks (3 timepoints).
Time frame: Every 6 weeks after initial dose
Assessment of radiologic response rate by PERCIST 1.0
Radiologic response rate determined by PERCIST 1.0 via PET scans (non-CT measurable participants)
Time frame: 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
Radioactivity in whole blood and plasma for each fractionated MNPR-101-PCTA-177Lu are projected via time-corrected gamma counts.
Time frame: for 2 weeks after each dose
To determine the maximum administered dose (MAD) for fractionated MNPR-101-PCTA-177Lu dosing
The maximum administered dose will be determined by the highest dose of MNPR-101-PCTA-177Lu not eliminated by TITE-BOIN.
Time frame: 6 weeks after the first dose
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