Perspective Therapeutics, Inc. is partnering with Bristol Myers Squibb (BMS) to evaluate [212Pb]VMT01 in combination with nivolumab (Opdivo, BMS) in patients with histologically confirmed melanoma and positive melanocortin 1 receptor (MC1R) imaging scans.
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.
Under the terms of the collaboration, Perspective will sponsor and fund the combination study and Bristol Myers Squibb will provide nivolumab for use in the study.
The study has completed enrollment in the first cohort and has commenced dosing in the second cohort.
“We see great potential for synergistic treatment effect with our novel, systemically delivered, MC1R-targeted alpha-particle radioligand therapy, [212Pb]VMT01, in combination with nivolumab, a well-studied immunotherapy,” says Markus Puhlmann, Chief Medical Officer of Perspective Therapeutics, in a news release. “Combination of [212Pb]VMT01 with immune checkpoint inhibitors in a PD-1/CTLA-4-resistant preclinical melanoma model has demonstrated potential to generate a number of complete responses, significantly arresting tumor growth and extending survival1,2. We look forward to expanding the clinical development of our radioligand therapy with standard of care immunotherapy to potentially bring novel solutions to patients suffering from this intractable disease.”
About the Phase 1/2a study of [212Pb]VMT01
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 positive MC1R imaging scans. The first part of the study is a dose escalation phase to determine the Maximum Tolerated radioactivity Dose (MTD) or Maximum Feasible radioactivity Dose (MFD) following a single administration of [212Pb]VMT01. Patients with stage IV or unresectable stage III metastatic melanoma who have progressed on at least 1 approved first-line therapy will be scheduled to receive up to 3 administrations of [212Pb]VMT01 approximately 8 weeks apart. The first patient cohort is scheduled to receive 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.
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).
