Perspective Therapeutics to pursue dose escalation in Phase 1/2a clinical trial

Perspective Therapeutics (CATX) announced initial results from its ongoing Phase 1/2a clinical trial of VMT-alpha-NET that are being presented at the 2024 North American Neuroendocrine Tumor Society Multidisciplinary NET Medical Symposium taking place November 21-23, 2024 in Chicago. VMT-alpha-NET is a somatostatin receptor type 2-targeted radiopharmaceutical therapy that can be radiolabeled with either 203Pb for patient selection and dosimetry assessments, or 212Pb for alpha-particle therapy. Perspective received Fast Track Designation for this program from the U.S. Food and Drug Administration based on preclinical data for SSTR2-positive neuroendocrine tumors regardless of prior treatment response. This Phase 1/2a clinical trial is a multi-center open-label dose escalation, dose expansion study of VMT-alpha-NET in patients with unresectable or metastatic SSTR2-positive NETs who have not received prior RPTs and have shown radiological evidence of disease progression in the 12 months prior to enrollment. Two patients were enrolled in Cohort 1, while seven patients were enrolled in Cohort 2. As of the data cut-off date for the NANETS presentation of October 31, 2024, eight patients had completed all four doses of treatment per the study protocol, while the remaining patient had completed three doses of treatment and will be scheduled to receive a fourth dose. As of the data cut-off date, scans were available to the study team for four patients after their fourth treatment, and post-final treatment scans were pending for the remaining five patients. Per the study protocol, two patients in Cohort 1 received administered activity of 2.5 mCi per dose regardless of body weight. Based on their respective body weights, the median administered activity per kilogram of weight was 45.5 microCi/kg per dose. Seven patients in Cohort 2 received administered activity of 5.0 mCi per dose regardless of body weight. Based on their respective body weights, the median administered activity per kilogram of weight was 62.1 microCi/kg per dose, ranging from 31.8 microCi/kg to 84.6 microCi/kg per dose. One patient in Cohort 2 received two doses of 84.6 microCi/kg per dose, then received the third and fourth doses at a reduced activity level of 42.4 microCi/kg per dose due to an adverse event that was determined by the investigator to be unrelated. Safety findings: No dose limiting toxicities (DLTs) were observed among any patients. No grade 4 or 5 treatment emergent adverse events or serious adverse events (SAEs) were observed. Two grade 3 adverse events (AEs) – one case of diarrhea and one case of syncope – were observed. No decline in renal function was observed. Hematologic AEs such as decreased lymphocyte count and anemia were all grades 1 and 2. No treatment discontinuations due to AEs have occurred. Activity has been observed with treatment. Eight of nine patients had durable control of disease. Six of nine patients had measurable reduction of tumor volume, one of whom had a confirmed response as defined by RECIST v1.1. The patient who experienced an objective response received the first two doses at 84.6 microCi/kg per dose, then received the remaining two doses at a reduced activity level of 42.4 microCi/kg. One patient was deemed to have progressive disease after one dose under RECIST v1.1, by unambiguous progression of non-target lesions. The Safety Monitoring Committee determined that safety observations during the DLT observation period supported proceeding with dose escalation to Cohort 3 and expanding the number of patients dosed at 5 mCi. Based on FDA interactions prior to trial initiation, the decision to open Cohort 3 will follow consultation and alignment with the agency.