Targeted Alpha-Particle Therapy for Advanced Somatostatin Receptor Type 2 (SSTR2) Positive Tumors ([212-Pb]-VMT)

A Phase I/IIa First-in-Human Study of [212Pb]VMT-α-NET Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Tumors

This study is Phase I/IIa First-in-Human Study of [212Pb]VMT-α-NET Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Tumors

Study Overview

• Status: Recruiting
• Conditions: Meningioma; Pheochromocytoma; Paraganglioma; Gastroenteropancreatic Neuroendocrine Tumor; Neuroendocrine Tumors Unresectable; Neuroendocrine Tumor Metastatic; Bronchial Neuroendocrine Tumor
• Intervention / Treatment: Drug: [203Pb]VMT-α-NET; Drug: [212Pb]VMT-α-NET

Detailed Description

This is a prospective, multi-center, open-label, radioactivity dose-finding/ dose expansion study of [212Pb]VMT-α-NET in up to approximately 300 adult subjects with unresectable or metastatic SSTR2-expressing tumors who have not received prior peptide receptor radionuclide therapy (PRRT).

Somatostatin Receptor type 2 (SSTR2) is highly expressed on various tumors including Neuroendocrine tumors (NETs), meningioma and therefore is an attractive therapeutic target. 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 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 with gastroenteropancreatic NETS, bronchial NETS, pheochromocytoma or paragangliomas, and meningioma. Subjects 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
• Enrollment (Estimated): 300
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: ClinicalTrials at Perspectivetherapeutics; Phone Number: (206) 676-0900; Email: clinicaltrials@perspectivetherapeutics.com

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic
      • Principal Investigator: Jason Starr, MD
      • Contact: Phone Number: 904-953-2000; Email: CANCERCTR@mayo.edu
    • Miami, Florida, United States, 33165
      • Recruiting
      • Biogenix Molecular
      • Principal Investigator: Frankis Almaguel, MD
      • Contact: Milka Vina; Phone Number: 786-791-1799; Email: mvina@cira-health.com
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • The University of Chicago
      • Principal Investigator: Chih-Yi Liao, MD
      • Contact: Phone Number: 773-702-1000; Email: cancerclinicaltrials@bsd.uchicago.edu
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
      • Principal Investigator: Yusuf Menda, MD
      • Contact: Phone Number: (319) 356-3214
      • Contact: Yusuf Menda; Phone Number: 319-356-1616; Email: yusuf-menda@uiowa.edu
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Recruiting
      • University of Kentucky
      • Contact: Yvonne Taul; Phone Number: 859-323-2354; Email: yvonne.taul@uky.edu
      • Principal Investigator: Lowell Anthony, MD, FACP
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • Johns Hopkins
      • Principal Investigator: Seyed Ali Mosallaie, MD
      • Contact: Phone Number: 410-955-6785; Email: smosall1@jhmi.edu
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Barbara Ann Karmanos Cancer Institute
      • Contact: Hannah Cressman; Phone Number: 313-576-8387; Email: cressmanh@karmanos.org
      • Principal Investigator: Anthony Shields, M.D., Ph.D
    • Grand Rapids, Michigan, United States, 49503
      • Recruiting
      • BAMF Health
      • Principal Investigator: Brandon Mancini, MD
      • Contact: BAMF Health Clinical Research Team; Phone Number: 616-330-2735; Email: researchclinicalteam@bamfhealth.com
    • Troy, Michigan, United States, 48098
      • Recruiting
      • Michigan Health Professionals
      • Principal Investigator: Savitha Balaraman, MD
      • Contact: Heather Austin; Phone Number: 585-216-7617; Email: heather.austin@profoundresearch.com
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Principal Investigator: Thorvardur R Halfdanarson, MD
      • Contact: Katie Wittenberger; Phone Number: 507-293-2512; Email: Wittenberger.Kathleen@mayo.edu
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University
      • Principal Investigator: Richard Wahl, MD
      • Contact: Callista Francis; Phone Number: 314-273-8797; Email: francisc@wustl.edu
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Recruiting
      • Nebraska Cancer Specialists
      • Principal Investigator: Samuel Mehr, MD
      • Contact: Scott Degenhardt, NMAA; Phone Number: 402-691-5257; Email: sdegenhardt@nebraskacancer.com
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • University of North Carolina
      • Principal Investigator: Jared Weiss, MD
      • Contact: Robert Huynh; Phone Number: 919-445-4936; Email: rhuynh@med.unc.edu
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • UH Cleveland Medical Center
      • Principal Investigator: Amr Mohamed, MD
      • Contact: Amr Mohamed; Phone Number: 216-844-3951; Email: Amr.Mohamed@UHhospitals.org
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University
      • Contact: Rajani Jacob; Phone Number: 614-366-3582; Email: Rajani.Jacob@osumc.edu
      • Principal Investigator: Vineeth Sukrithan, M.D.
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt-Ingram Cancer Center
      • Principal Investigator: Robert Ramirez, DO
      • Contact: Patient Liaison Advisor; Phone Number: 800-811-8480; Email: cip@vumc.org
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists
      • Contact: Carrie Friedman; Phone Number: 703-636-1473; Email: carrie.friedman@usoncology.com
      • Principal Investigator: Gregory Sibley, MD
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutchinson Cancer Center
      • Contact: Heather White; Phone Number: 206-667-5534; Email: nucmedresearch@fredhutch.org
      • Principal Investigator: Amir Iranvani, MD
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Froedtert Medical College of Wisconsin
      • Contact: Dawn Carini; Phone Number: 414-805-0789; Email: dcarini@mcw.edu
      • Principal Investigator: Alexandria Phan, MD, FACP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult (ages ≥18) PRRT-naïve subjects with NETs or meningioma by local pathology.
2. Disease described clinically as: (a) Locally advanced/unresectable or metastatic NETs for dose-finding part of the study (b) Locally advanced/unresectable or metastatic GEP-NETs, bronchial NETs, pheochromocytoma, or paragangliomas for the dose-expansion part of the study (c) Requiring at least 1 prior surgery (resection/biopsy) and a maximum of 1 line of EBRT, if technically feasible, for meningioma.
3. For meningioma: histologically confirmed diagnosis of meningioma, i.e., all grades (1 to 3) per World Health Organization Classification of Tumors of the Central Nervous System (5th edition; WHO-CNS5)
4. Radiological evidence of measurable disease by: (a) For NETs: RECIST v1.1 criteria on CT with contrast or MRI of the areas of tumor involvement within 60 days of enrollment.
5. Lesions must have shown radiological evidence of disease progression in the 12 months prior to enrollment. (b) For meningioma: RANO meningioma criteria on contrast-enhanced skull MRI for meningioma within 3 weeks prior to enrollment.
6. Demonstration of lesional SSTR expression: (a) For NETs: using an FDA-approved somatostatin receptor PET imaging agent, e.g. [68Ga]DOTATATE, [64Cu]DOTATATE, or [68Ga]DOTATOC (b) For meningioma: using a standard-of-care SSTR PET imaging agent within 45 days of enrollment
7. ECOG Performance Status ≤ 1.
8. Subjects with HIV positivity are allowed if CD4 Count > 350 cells/μL.
9. Concurrent Somatostatin Analog (SSA) Therapy use while on protocol therapy is allowed provided that the subject must be able to tolerate withholding long-acting SSA therapy for a minimum of 28 days and short-acting SSA therapy for a minimum of 24 hours before the first and subsequent administrations of [203Pb]VMT-α-NET or [212Pb]VMT-α-NET
10. For NETs: Progressive Disease on approved therapies other than radionuclide therapy.
11. For subjects with meningioma who are receiving corticosteroid treatment, the dose must be ≤ 4 mg/day dexamethasone (or other corticosteroid equivalent dose) for a minimum of 7 days before the initiation of study treatment.
12. Must have clinically demonstrated adequate catecholamine blockade if catecholamine-secreting pheochromocytoma/paraganglioma tumors are present.
13. Able to understand and sign informed consent and comply with all study requirements.
14. Life expectancy > 3 months.
15. Satisfactory organ function as determined by laboratory testing.
16. For females of reproductive potential: agree to use of highly effective contraception and refrain from donating eggs (ova, oocytes) for the purpose of reproduction starting from screening, during treatment, and for at least 6 months after the last dose of [212Pb]VMT-α-NET
17. For males of reproductive potential: agree to use of condoms or other methods to ensure effective contraception with partner and refrain from donating sperm starting from screening, during treatment, and for at least 6 months after the last dose of [212Pb]VMT-α-NET

Exclusion Criteria:

1. Known hypersensitivity to SSA, SSTR imaging agents or any of the excipients of [212Pb]VMT-α-NET.
2. Known additional malignancy that is progressing or requires active treatment.
3. Pregnancy or breastfeeding a child.
4. Febrile illness within 48 hours of any scheduled [212Pb]VMT-α-NET administration should be rescheduled > 48 hours after resolution of fever].
5. Treatment with another investigational medicinal product within 30 days of anticipated treatment.
6. Prior treatment with systemic PRRT based therapies (i.e., [90Y] DOTATATE/DOTATOC or [177Lu] DOTATATE)
7. Prior treatment with 90-Yttrium radioembolization must be completed at least 6 months prior to enrollment.
8. External beam radiation therapy (EBRT) must be completed at least 30 days prior to enrollment.
9. Subjects who have received prior treatment with 90Y radioembolization or EBRT should have radiation absorbed dose to critical organs documented.
10. Prior treatment with systemic anticancer therapy must be completed at least 30 days prior to enrollment (except for SSAs in subjects with functional tumors).
11. Major surgery must be completed at least 30 days prior to enrollment.
12. For Subjects with NETs: Known brain metastases; unless these metastases have been treated and stabilized 6 months prior to enrollment and the subject has been off steroid support for at least 14 days prior to enrollment.
13. Recently diagnosed and active infections requiring a time-limited course of antifungals or antibiotics in the 3 days prior to enrollment.
14. Receipt of live attenuated vaccines in the 7 days prior to enrollment.
15. Grade 3 nausea/vomiting or diarrhea within 72 hours before the of first scheduled dose of [212Pb]VMT-α-NET despite adequate antiemetic and other supportive care
16. Known medical condition which would make this protocol unreasonably hazardous for the subject.
17. Medical history of a condition resulting in a severe allergic reaction such as anaphylaxis or angioedema to known components of the Investigational Medicinal Product or excipients.
18. Current abuse of alcohol or illicit drugs (exclusive of use of medically prescribed cannabinoids).
19. Existence of any medical or social issues likely to interfere with study conduct or that may cause increased risk to the subject or to others, e.g., lack of ability to follow radiation safety precautions.
20. QTc > 450 milliseconds for males and females.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Finding; Dose Finding to determine OBD and potential RP2D in up to 200 patients receiving up to 4 administrations of [212Pb]VMT-α-NET approximately 8 weeks apart. A dosimetry sub-study utilizing [203Pb]VMT-α-NET is incorporated into the study.	Drug: [203Pb]VMT-α-NET; [203Pb]VMT-α-NET is administered by intravenous bolus injection for single-photon emission computed tomography imaging.; Drug: [212Pb]VMT-α-NET; [212Pb]VMT-α-NET is administered by intravenous infusion for treatment of SSTR2 expressing tumors.
Experimental: Dose Expansion; Dose up to 100 subjects (gastroenteropancreatic NETs, bronchial NETs, and pheochromocytoma or paraganglioma and meningioma) at RP2D for further assessment of safety and preliminary efficacy.	Drug: [203Pb]VMT-α-NET; [203Pb]VMT-α-NET is administered by intravenous bolus injection for single-photon emission computed tomography imaging.; Drug: [212Pb]VMT-α-NET; [212Pb]VMT-α-NET is administered by intravenous infusion for treatment of SSTR2 expressing tumors.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Incidence and severity of DLTs during the first 42 days of study treatment will be assessed.
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.	Until the end of study (3 years after end-of-study visit)
Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 in subjects with NETs	Percentage of subjects with complete responses (CRs) or partial responses (PRs) to at least 1 administration of [212Pb]VMT-α-NET	Up to week 96
ORR per Response Assessment in Neuro-Oncology (RANO) meningioma criteria in subjects with meningioma	Percentage of subjects with complete responses (CRs) or partial responses (PRs) to at least 1 administration of [212Pb]VMT-α-NET	Up to week 96

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	24 hours following [212Pb]VMT-α-NET dosing.
Anti-tumor efficacy of [212Pb]VMT-α-NET in terms of tumor response	Determination of the best overall response rate (BOR) by RECIST v1.1 in subjects with neuroendocrine tumors or RANO in meningioma subjects	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 or RANO	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 or RANO	Up to week 96

Collaborators and Investigators

• Sponsor: Perspective Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2023
• Primary Completion (Estimated): November 26, 2029
• Study Completion (Estimated): December 26, 2029

Study Registration Dates

• First Submitted: November 15, 2022
• First Submitted That Met QC Criteria: November 23, 2022
• First Posted (Actual): December 5, 2022

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Radiotherapy; Meningioma; Neuroendocrine Tumors; Pb-203; Theranostics; Radiopharmaceuticals; Metastatic Neuroendocrine Tumors; Pb-212; Alpha Particle Therapy; Somatostatin Receptor Type 2 (SSTR2); [212Pb]VMT-α-NET; VMT-α-NET-T01
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Pheochromocytoma; Neuroendocrine Tumors; Paraganglioma; Meningioma; Gastro-enteropancreatic neuroendocrine tumor
• Other Study ID Numbers: VMT-α-NET-T101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Protocol, CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No