Targeted Alpha-Particle Therapy for Advanced Somatostatin Receptor Type 2 (SSTR2) Positive Neuroendocrine Tumors

NCT ID: NCT05636618

Last Updated: 2025-11-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

260 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-09-27

Study Completion Date

2029-12-26

Brief Summary

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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

Detailed Description

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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.

Conditions

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Neuroendocrine Tumors Unresectable Neuroendocrine Tumor Metastatic Gastroenteropancreatic Neuroendocrine Tumor Bronchial Neuroendocrine Tumor Paraganglioma Pheochromocytoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

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

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

[203Pb]VMT-α-NET

Intervention Type DRUG

\[203Pb\]VMT-α-NET is administered by intravenous bolus injection for single-photon emission computed tomography imaging.

[212Pb]VMT-α-NET

Intervention Type DRUG

\[212Pb\]VMT-α-NET is administered by intravenous infusion for treatment of SSTR2 expressing neuroendocrine tumors.

Dose Expansion

Dose with up to 60 subjects at RP2D for further assessment of safety and preliminary efficacy.

Group Type EXPERIMENTAL

[203Pb]VMT-α-NET

Intervention Type DRUG

\[203Pb\]VMT-α-NET is administered by intravenous bolus injection for single-photon emission computed tomography imaging.

[212Pb]VMT-α-NET

Intervention Type DRUG

\[212Pb\]VMT-α-NET is administered by intravenous infusion for treatment of SSTR2 expressing neuroendocrine tumors.

Interventions

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[203Pb]VMT-α-NET

\[203Pb\]VMT-α-NET is administered by intravenous bolus injection for single-photon emission computed tomography imaging.

Intervention Type DRUG

[212Pb]VMT-α-NET

\[212Pb\]VMT-α-NET is administered by intravenous infusion for treatment of SSTR2 expressing neuroendocrine tumors.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Adult (ages ≥18) PRRT-naïve subjects with NETs by local pathology.
2. Locally advanced/unresectable or metastatic NETs.
3. Radiological evidence of measurable disease by RECIST v1.1 criteria on CT with contrast or MRI of the areas of tumor involvement within 60 days of enrollment.
4. Lesions must have shown radiological evidence of disease progression in the 12 months prior to enrollment.
5. Demonstration of lesional SSTR2 expression using an FDA-approved somatostatin receptor PET imaging agent, e.g. \[68Ga\]DOTATATE, \[64Cu\]DOTATATE, or \[68Ga\]DOTATOC, (SSTR2 positivity defined as uptake \> background liver) obtained and interpreted in accordance with product labeling and appropriate clinical use criteria within 12 months of enrollment.
6. ECOG Performance Status ≤ 1.
7. Subjects with HIV positivity are allowed if CD4 Count \> 350 cells/μL.
8. Concurrent Somatostatin Analog (SSA) Therapy use while on protocol therapy is allowed provided that the subject 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
9. Progressive Disease on approved therapies other than radionuclide therapy.
10. Must have clinically demonstrated adequate catecholamine blockade if catecholamine-secreting pheochromocytoma/paraganglioma tumors are present.
11. Able to understand and sign informed consent and comply with all study requirements.
12. Life expectancy \> 3 months.
13. Satisfactory organ function as determined by laboratory testing.
14. 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
15. 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. Active secondary malignancy.
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 must be completed at least 30 days prior to enrollment.
9. Prior treatment with systemic anticancer therapy must be completed at least 30 days prior to enrollment (except for SSAs in subjects with functional tumors).
10. Major surgery must be completed at least 30 days prior to enrollment.
11. 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.
12. Recently diagnosed and active infections requiring a time-limited course of antifungals or antibiotics in the 3 days prior to enrollment.
13. Receipt of live attenuated vaccines in the 7 days prior to enrollment.
14. 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
15. Known medical condition which would make this protocol unreasonably hazardous for the subject.
16. 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.
17. Current abuse of alcohol or illicit drugs (exclusive of use of medically prescribed cannabinoids).
18. 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.
19. QTc \> 450 milliseconds for males and females.
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Perspective Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Mayo Clinic

Jacksonville, Florida, United States

Site Status RECRUITING

Biogenix Molecular

Miami, Florida, United States

Site Status RECRUITING

The University of Chicago

Chicago, Illinois, United States

Site Status RECRUITING

University of Iowa

Iowa City, Iowa, United States

Site Status RECRUITING

University of Kentucky

Lexington, Kentucky, United States

Site Status RECRUITING

Johns Hopkins

Baltimore, Maryland, United States

Site Status RECRUITING

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status RECRUITING

BAMF Health

Grand Rapids, Michigan, United States

Site Status RECRUITING

Michigan Health Professionals

Troy, Michigan, United States

Site Status RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

Site Status RECRUITING

Washington University

St Louis, Missouri, United States

Site Status RECRUITING

Nebraska Cancer Specialists

Omaha, Nebraska, United States

Site Status RECRUITING

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status RECRUITING

Ohio State University

Columbus, Ohio, United States

Site Status RECRUITING

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, United States

Site Status RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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ClinicalTrials at Perspectivetherapeutics

Role: CONTACT

(206) 676-0900

Facility Contacts

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Role: primary

904-953-2000

Milka Vina

Role: primary

786-791-1799

Role: primary

773-702-1000

Yusuf Menda

Role: primary

319-356-1616

Role: backup

(319) 356-3214

Yvonne Taul

Role: primary

859-323-2354

Role: primary

410-955-6785

Hannah Cressman

Role: primary

313-576-8387

BAMF Health Clinical Research Team

Role: primary

616-330-2735

Heather Austin

Role: primary

585-216-7617

Katie Wittenberger

Role: primary

507-293-2512

Callista Francis

Role: primary

314-273-8797

Scott Degenhardt, NMAA

Role: primary

402-691-5257

Robert Huynh

Role: primary

919-445-4936

Rajani Jacob

Role: primary

614-366-3582

Patient Liaison Advisor

Role: primary

800-811-8480

Carrie Friedman

Role: primary

703-636-1473

Heather White

Role: primary

206-667-5534

Other Identifiers

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VMT-α-NET-T101

Identifier Type: -

Identifier Source: org_study_id

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