Perspective Therapeutics presents initial results from Phase 1/2a study of VMT01

Perspective Therapeutics announced that initial results from its Phase 1/2a study of VMT01 are being presented at the 21st International Congress of the Society for Melanoma Research, being held on October 10-13, 2024 in New Orleans, Louisiana. VMT01 is a MC1R-targeted radiopharmaceutical therapy that can be radiolabeled with either 203Pb for patient selection and dosimetry assessments, or 212Pb for alpha particle therapy. In preclinical experiments VMT01 demonstrated efficacy via two distinct mechanisms of action: direct cell killing at high radiation doses and through immunostimulatory low-dose induction of immune-mediated cell death. Efficacy was augmented by immune checkpoint inhibitors. On the basis of these results, the U.S. Food and Drug Administration granted Fast Track Designation for the clinical development of VMT01. This study is a multi-center, open-label dose escalation, dose expansion study in patients with histologically confirmed melanoma and MC1R-positive imaging scans. Patients were required to have already received standard of care. Eligible patients may receive up to three treatments with VMT01, eight weeks apart. Three patients were enrolled in Cohort 1, while seven patients were enrolled in Cohort 2. Patients in each cohort received a median of five prior lines of systematic therapy, including a median of three prior lines of immunotherapy. Safety findings: No dose limiting toxicities were observed among any patients, and no adverse events led to treatment discontinuation. Treatment emergent adverse events were mostly Grades 1 and 2. None of the four cases of grade 3 TEAEs were deemed to be treatment related. There were no grade 4 or 5 TEAEs. No renal toxicities have been reported to date in spite of dosimetry estimated renal radiation that approached the higher end of conventional dosing. Efficacy findings: All patients in Cohort 1 completed three treatments, with one patient experiencing a RECIST version 1.1 objective response after completion of treatment, and two patients experiencing stable disease at 9 and 11 months from the start of treatment, respectively. In Cohort 2, patients progressed after either the first cycle or the second cycle. These findings are consistent with published and ongoing preclinical studies showing immunostimulatory effects at lower radiation doses. The Safety Monitoring Committee has reviewed these findings. The SMC recommended exploring a lower dose level of 1.5 mCi per dose, which is lower than the dose administered in Cohort 1, both as a single agent and in combination with the anti-PD-1 antibody, nivolumab. The SMC recommendation would allow for the monotherapy and combination cohorts to proceed concurrently. An amendment to further explore lower dose levels for monotherapy is planned. The combination cohort at 1.5 mCi per dose with nivolumab is active and now open for enrollment.