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

NCT05636618 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: VMT-α-NET-T101
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 19

Brief Summary

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

Conditions

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

Keywords

Radiopharmaceuticals; Somatostatin Receptor Type 2 (SSTR2); Neuroendocrine Tumors; Metastatic Neuroendocrine Tumors; Pb-212; Theranostics; Alpha Particle Therapy; Radiotherapy; [212Pb]VMT-α-NET; VMT-α-NET-T01; Pb-203; Meningioma

Outcome Measures

Primary Outcomes (4)

• 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.

• 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

• 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)

Secondary Outcomes (5)

• Anti-tumor efficacy of [212Pb]VMT-α-NET in terms of tumor response

  Until the end of study (3 years after end-of-study visit)

• Determine the duration of response (DOR) receiving [212Pb]VMT-α-NET.

  Up to week 96

• Determination of Progression-free survival (PFS)

  Up to week 96

• To investigate the Overall Survival (OS) following treatment with [212Pb]VMT-α-NET

  Until the end of study (3 years after end-of-study visit)

• Determination of pharmacokinetic properties of [212Pb]VMT-α-NET.

  24 hours following [212Pb]VMT-α-NET dosing.

Study Arms (2)

Dose Finding

EXPERIMENTAL

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; Drug: [212Pb]VMT-α-NET

Dose Expansion

EXPERIMENTAL

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; Drug: [212Pb]VMT-α-NET

Interventions

[203Pb]VMT-α-NET DRUG

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

Dose Expansion; Dose Finding

[212Pb]VMT-α-NET DRUG

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

Dose Expansion; Dose Finding

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult (ages ≥18) PRRT-naïve subjects with NETs or meningioma by local pathology.
• 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.
• 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)
• 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.
• 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.
• 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
• ECOG Performance Status ≤ 1.
• Subjects with HIV positivity are allowed if CD4 Count \> 350 cells/μL.
• 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
• For NETs: Progressive Disease on approved therapies other than radionuclide therapy.
• 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.
• Must have clinically demonstrated adequate catecholamine blockade if catecholamine-secreting pheochromocytoma/paraganglioma tumors are present.
• Able to understand and sign informed consent and comply with all study requirements.
• Life expectancy \> 3 months.
• Satisfactory organ function as determined by laboratory testing.

You may not qualify if:

• Known hypersensitivity to SSA, SSTR imaging agents or any of the excipients of \[212Pb\]VMT-α-NET.
• Known additional malignancy that is progressing or requires active treatment.
• Pregnancy or breastfeeding a child.
• Febrile illness within 48 hours of any scheduled \[212Pb\]VMT-α-NET administration should be rescheduled \> 48 hours after resolution of fever\].
• Treatment with another investigational medicinal product within 30 days of anticipated treatment.
• Prior treatment with systemic PRRT based therapies (i.e., \[90Y\] DOTATATE/DOTATOC or \[177Lu\] DOTATATE)
• Prior treatment with 90-Yttrium radioembolization must be completed at least 6 months prior to enrollment.
• External beam radiation therapy (EBRT) must be completed at least 30 days prior to enrollment.
• Subjects who have received prior treatment with 90Y radioembolization or EBRT should have radiation absorbed dose to critical organs documented.
• Prior treatment with systemic anticancer therapy must be completed at least 30 days prior to enrollment (except for SSAs in subjects with functional tumors).
• Major surgery must be completed at least 30 days prior to enrollment.
• 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.
• Recently diagnosed and active infections requiring a time-limited course of antifungals or antibiotics in the 3 days prior to enrollment.
• Receipt of live attenuated vaccines in the 7 days prior to enrollment.
• 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

Sponsors & Collaborators

• Perspective Therapeutics: lead

Study Sites (19)

Mayo Clinic

Jacksonville, Florida, 32224, United States

RECRUITING

Biogenix Molecular

Miami, Florida, 33165, United States

RECRUITING

The University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

University of Kentucky

Lexington, Kentucky, 40536, United States

RECRUITING

Johns Hopkins

Baltimore, Maryland, 21287, United States

RECRUITING

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

BAMF Health

Grand Rapids, Michigan, 49503, United States

RECRUITING

Michigan Health Professionals

Troy, Michigan, 48098, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

RECRUITING

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

RECRUITING

UH Cleveland Medical Center

Cleveland, Ohio, 44106, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

Froedtert Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Gastro-enteropancreatic neuroendocrine tumor; Paraganglioma; Pheochromocytoma; Meningioma; Neuroendocrine Tumors

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases

Central Study Contacts

ClinicalTrials at Perspectivetherapeutics

CONTACT

(206) 676-0900; clinicaltrials@perspectivetherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: November 15, 2022
• First Posted: December 5, 2022
• Study Start: September 27, 2023
• Primary Completion (Estimated): November 26, 2029
• Study Completion (Estimated): December 26, 2029
• Last Updated: May 14, 2026

Record last verified: 2026-05

Locations

US (19)