Perspective Therapeutics, Inc. announced that it began patient recruitment for the second dosing cohorts (Cohort 2) in clinical studies for both of its lead product candidates, [212Pb]VMT-a-NET and [212Pb]VMT01, after the safety monitoring committees for each study unanimously recommended moving forward. In addition, the first patient in cohort 2 of the [212Pb]VMT01 study was already dosed. [212Pb]VMT-a-NET is a targeted alpha particle therapy (TAT) in development for patients with unresectable or metastatic somatostatin receptor type 2 (SSTR2) expressing tumors who have not previously received peptide-targeted radiopharmaceutical therapy, such as Lutathera.

[212Pb]VMT01 is a TAT in development for second-line or later treatment of patients with progressive MC1R-positive metastatic melanoma. This is a multi-center open-label study (clinicaltrials.gov identifier NCT05636618) of [212Pb]VMT-a-NET, a targeted alpha particle therapy, for patients with advanced SSTR2-positive neuroendocrine tumors. The first part of the study involves dose-escalation designed to determine the maximum tolerated dose (MTD) or maximum feasible dose (MFD) following a single administration of [212Pb]VMT-a-NET.

The first patient cohort received 111 MBq (3mCi) per dose. The second cohort will receive administered activities of 185 MBq (5mCi), with cohorts 3 and 4 receiving 370 MBq (10 mCi) and 555 MBq (15 mCi), respectively, if the MTD or MFD is not reached during escalation. According to the modified toxicity probability interval 2 (mTPI-2) study design, intermediate de-escalation doses are also possible to allow selection of the optimal activity dose to take forward into the dose expansion part of the study.

The second part of the study is a dose expansion phase based on the identified MTD/MFD. Patients with positive uptake on FDA-approved SSTR2 PET/CT will receive a fixed dose of [212Pb]VMT-a-NET IV administered at the recommended Phase 2 dose and schedule determined in the Phase I dose escalation. This ongoing trial (clinicaltrials.gov identifier NCT05655312) is a multi-center open-label dose escalation, dose expansion study of [212Pb]VMT01 in subjects with histologically confirmed melanoma and MC1R-positive imaging scans.

The first part of the study is a dose escalation phase to determine the MTD or MFD following a single administration of [212Pb]VMT01. The first patient cohort received 111 MBq (3mCi) per dose. The second cohort will receive administered activities of 185 MBq (5mCi), with cohorts 3 and 4 receiving 370 MBq (10 mCi) and 555 MBq (15 mCi) respectively, if the MTD or MFD is not reached during escalation.

According to the modified toxicity probability interval 2 (mTPI-2) study design, intermediate de-escalation doses are also possible to allow selection of the optimal activity dose to take forward into the dose expansion part of the study. The second part of the study is a dose expansion phase based on the identified MTD/MFD. Patients may be eligible to receive up to three administrations of [212Pb]VMT01 approximately eight weeks apart.

A dosimetry sub-study is included to assess biodistribution, tumor uptake and correlation of uptake with observed toxicities and efficacy. About Neuroendocrine Tumors: Neuroendocrine tumors form in cells that interact with the nervous system or in glands that produce hormones. They can originate in various parts of the body, most often in the gut or the lungs and can be benign or malignant.

Neuroendocrine tumors are typically classified as pancreatic neuroendocrine tumors or non-pancreatic neuroendocrine tumors. According to cancer.net, it is estimated that more than 12,000 people in the United States are diagnosed with a NET each year. Importantly, neuroendocrine tumors are associated with a relatively long duration of survival compared to other tumors and as a result, there are approximately 175,000 people living with this diagnosis.

Melanoma is a cancer of the skin arising from uncontrollable growth of melanocytes, the melanin producing cells of the body. Metastatic melanoma is the result of melanoma that has progressed through the layers of skin, infiltrated the blood stream or lymphatic system, and traveled to other areas of the body to metastasize. In the United States, there are approximately 100,000 new diagnoses of melanoma annually and approximately 6,850 deaths annually from metastatic melanoma (cancer.org).

In most cases, metastatic melanoma cannot be cured but treatment can support a longer life. VMT-a-NET is a clinical stage targeted alpha particle therapy (TAT) radiopharmaceutical being developed for the treatment and diagnosis of somatostatin receptor subtype 2 (SSTR2) expressing neuroendocrine tumors, which are a rare and difficult-to-treat type of cancer. VMT-a-NET incorporates Perspective Therapeutics' proprietary lead-specific chelator (PSC) to bind 203Pb for SPECT imaging, and 212Pb for alpha particle therapy.

VMT01 is a proprietary clinical-stage low molecular weight peptide that is targeted to the melanocortin subtype 1 receptor (MC1R) which is over-expressed on melanoma cells. VMT01 is in development for the treatment and diagnosis of MC1R-positive metastatic melanoma. VMT01 can be labeled with 212Pb to deliver alpha-particle radiation directly to tumor cells, or 203Pb to enable patient selection, diagnostic imaging and dosimetry via SPECT imaging.

The product recently completed a pilot imaging study at the Mayo Clinic Rochester, MN. In August 2023, the Company announced that the first patient was dosed in the Phase1/2a study of VMT01 (clinicaltrials.gov identifier NCT05655312).