This study is Phase I/IIa First-in-Human Study of \[212Pb\]VMT-α-NET Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Neuroendocrine Tumors
This is a prospective, multi-center, open-label, radioactivity dose-finding/ dose expansion study of \[212Pb\]VMT-α-NET in up to 260 adult subjects with unresectable or metastatic SSTR2-expressing neuroendocrine tumors (NETs) who have not received prior peptide receptor radionuclide therapy (PRRT). Somatostatin Receptor type 2 (SSTR2) is highly expressed on various tumors including NETs and therefore is an attractive therapeutic target for NET treatment. Lead-212 (\[212Pb\]-) based peptide-radiopharmaceuticals are an emerging class of targeted alpha-particle cancer therapies that have potential to improve delivery of a highly effective form of radiation. \[212Pb\] VMT-a-NET is a targeted alpha therapy agent designed to enhance the precision and effectiveness of cancer treatment by delivering a highly potent form of radiation directly to cancer cells. This approach aims to maximize radiation delivery to tumors while minimizing exposure to healthy tissues. The study will be conducted in 2 parts: Part 1: Phase I Dose-Finding: Subjects will receive radioactive doses of \[212Pb\]VMT-α-NET up to a maximum dose of 222 MBq (6 mCi) for dose-limiting toxicity (DLT) observation, determining Optimal Biological Dose (OBD) and potential Recommended Phase 2 Dose (RP2D) for Part 2 (Dose Expansion). Dose changes or adjustments will be made by the safety monitoring committee (SMC) and Sponsor. The RP2D will be determined following a holistic analysis of observed DLTs, adverse events (AEs), estimated cumulative organ radiation exposure, and efficacy signals over the course of all treatment cycles for all dose cohorts. Part 2: Phase IIa Dose-Expansion: This part will enroll subjects who will receive RP2D identified in Part 1 for further assessment of safety and preliminary efficacy. Reno-protective amino acids will be co-administered prior to each \[212Pb\]VMT-α-NET dose in all subjects. Dose-finding will be based on an adaptive design until optimal biologic dose is identified or the pre-specified rules are met. A dosimetry sub-study using \[203Pb\]VMT-α-NET will be conducted. The subjects will undergo dosimetric evaluation prior to receiving the therapeutic agent.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
260
\[203Pb\]VMT-α-NET is administered by intravenous bolus injection for single-photon emission computed tomography imaging.
\[212Pb\]VMT-α-NET is administered by intravenous infusion for treatment of SSTR2 expressing neuroendocrine tumors.
Mayo Clinic
Jacksonville, Florida, United States
RECRUITINGBiogenix Molecular
Miami, Florida, United States
RECRUITINGThe University of Chicago
Chicago, Illinois, United States
RECRUITINGUniversity of Iowa
Iowa City, Iowa, United States
RECRUITINGUniversity of Kentucky
Lexington, Kentucky, United States
RECRUITINGJohns Hopkins
Baltimore, Maryland, United States
RECRUITINGBarbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
RECRUITINGBAMF Health
Grand Rapids, Michigan, United States
RECRUITINGMichigan Health Professionals
Troy, Michigan, United States
RECRUITINGMayo Clinic
Rochester, Minnesota, United States
RECRUITING...and 7 more locations
Number of participants with dose-limiting toxicities (DLTs) after the first administration of [212Pb]VMT-α-NET
DLTs describe side effects of a drug that are serious enough to prevent an increase in dose
Time frame: Incidence and severity of DLTs during the first 42 days of study treatment will be assessed.
Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1
Percentage of subjects with complete responses (CRs) or partial responses (PRs) to at least 1 administration of \[212Pb\]VMT-α-NET
Time frame: Up to week 96
Number of subjects with adverse events (AEs)
Any untoward medical occurrence in a clinical investigational participant administered \[212Pb\]VMT-α-NET and which does not necessarily have a causal relationship with this treatment. Associated Adverse Events (AE) or Serious AEs are assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
Time frame: Until the end of study (3 years after end-of-study visit)
Anti-tumor efficacy of [212Pb]VMT-α-NET in terms of tumor response
Determination of the overall response rate (ORR) by RECIST v1.1 in subjects with neuroendocrine tumors
Time frame: Until the end of study (3 years after end-of-study visit)
Determine the duration of response (DOR) receiving [212Pb]VMT-α-NET.
The length of time that a tumor continues to respond to treatment without the cancer growing or spreading determined by RECIST v1.1
Time frame: Up to week 96
Determination of Progression-free survival (PFS)
PFS is how long a subject lives without the disease worsening as evaluated by RECIST v1.1
Time frame: Up to week 96
To investigate the Overall Survival (OS) following treatment with [212Pb]VMT-α-NET
OS is how long a subject lives after a subject starts treatment
Time frame: Until the end of study (3 years after end-of-study visit)
Determination of pharmacokinetic properties of [212Pb]VMT-α-NET.
Blood radioactivity pharmacokinetic parameter i.e. area under the plasma concentration versus time curve (AUC) is determined.
Time frame: 24 hours following [212Pb]VMT-α-NET dosing.
ClinicalTrials at Perspectivetherapeutics
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