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About the Phase 1/2a Study of [212Pb]VMT-α-NET
Trial Name: A Phase I/IIa First-in-Human Study of [212Pb]VMT-α-NET Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Neuroendocrine Tumors
ClinicalTrials.gov Identifier: NCT05636618
Sponsor: Perspective Therapeutics
Completion Date: January 31, 2028
Contact: Markus Puhlmann, MD, MBA,(319) 665-2150, firstname.lastname@example.org
Cohort 1 dosing has been completed in the phase 1/2a trial (NCT05636618) evaluating [212Pb]VMT-α-NET in patients with unresectable or metastatic somatostatin receptor type 2 (SSTR2)-expressing neuroendocrine tumors (NETs), according to Perspective Therapeutics, Inc.1
“We are pleased with the progress of our cCompany-sponsored clinical evaluation of [212Pb]VMT-α-NET in patients with difficult-to-treat SSTR2-expressing NETs. The rapid recruitment into this study reflects the demand for potent alpha-particle therapies that exists in this patient population,” commented Markus Puhlmann, chief medical officer of Perspective Therapeutics, in a press release.
[212Pb]VMT-α-NET is a targeted alpha-particle therapy in development for patients with advanced SSTR2-positive NETS.
In the multicenter, open-label, trial, [212Pb]VMT-α-NET is being evaluated in 2 parts: dose-escalation and dose-expansion portions. The first part is the dose-escalation phase where investigators aim to determine the maximum tolerated dose (MTD) or maximum feasible dose (MFD) after single-agent [212Pb]VMT-α-NET is given to patients.2
Patients not previously treated with peptide receptor radionuclide therapy will be scheduled to receive up to 4 administrations of [212Pb]VMT-α-NET approximately 8 weeks apart. In the first cohort, patients received 111 MBq (3mCi) per dose, and in the second cohort, patients will receive administered activities of 185 MBq (5mCi). If the MTD or MFD is not reached during dose-escalation, patients in cohorts 3 and 4 will be treated with 370 MBq (10 mCi) and 555 MBq (15 mCi), respectively.
The dose-expansion phase of the study will use the identified MTD/MFD determined in the dose-escalation phase. A fixed dose of [212Pb]VMT-α-NET given via intravenous infusion will be administered to patients with positive uptake on FDA-approved SSTR2 PET/CT.
Enrollment in the trial is open to patients aged 18 years and older with locally advanced/unresectable or metastatic NETs who have radiological evidence of measurable disease by RECIST v1.1, lesions that have shown radiological evidence of disease progression in the 12 months prior to enrollment, and an ECOG performance status 0-2. Other requirements include having progressive disease on approved therapies other than radionuclide therapy, adequate catecholamine blockade if catecholamine-secreting pheochromocytoma/paraganglioma tumors are present, and a life expectancy > 3 months.
Patients who are HIV-positive are allowed to enroll if their CD4 count is > 500 cells/μL. Administration of, long-acting somatostatin analogues are allowed but must be stopped within 30 days prior to [68Ga]DOTATATE PET/CT (or another SSTR2-PET), if clinically possible, while short-acting somatostatin analogues should be withheld for 24 hours.
Primary end points of the study include number of patients with adverse events, laboratory abnormalities, dose-limiting toxicities, and area under the concentration-time curve. Secondary end points include antitumor efficacy, duration of response, progression-free survival, and biodistribution of [212Pb]VMT-α-NET using a microdose of the therapeutic surrogate.
“We are grateful to our collaborator, Nikolaos Trikalinos, MD, mMedical oOncologist at Washington University in St. Louis, who serves as the referring medical oncologist for the study and ensures that patients can access our potentially life-changing therapeutic. With both of our investigational therapies, [212Pb]VMT-α-NET and [212Pb]VMT01, now having completed their first cohorts, we look forward to generating data at higher doses early in 2024,” added Puhlmann in a press release.1
In addition to this phase 1/2 study, the first dose-escalation cohort for Perspective’s melanoma therapeutic [212Pb]VMT01 was recently completed. The cCompany also has 2 active clinical trial sites for the trial and anticipates 2 more to become operational in December, at the same time cohort 2 is started.
Perspective Therapeutics, Inc, remains on track to launch an additional 14 clinical trial sites throughout the United States.
1. Perspective Therapeutics completes initial dose escalation cohort for second novel targeted alpha therapy. News release. Perspective Therapeutics, Inc. November 16, 2023. Accessed November 16, 2023. https://tinyurl.com/4462bfny
2. Targeted alpha-particle therapy for advanced SSTR2 positive neuroendocrine tumors (212-Pb-VMT). ClinicalTrials.gov. Updated November 8, 2023. Accessed November 16, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05636618