Perspective Therapeutics and PMV Pharma Provide Clinical Trial Updates

Perspective Therapeutics and PMV Pharmaceuticals have recently provided updates on their respective clinical trial programs, highlighting progress in radiopharmaceutical therapies and precision oncology.

Perspective Therapeutics Advances Radiopharmaceutical Pipeline

Perspective Therapeutics, a radiopharmaceutical company, is advancing its pipeline with multiple clinical updates expected in the next 12-18 months. Thijs Spoor, CEO of Perspective, stated, "2025 is just the beginning of the next chapter for our team and the patients we serve." The company's strategic priorities include advancing clinical programs and expanding manufacturing capabilities.

VMT-α-NET Program Update

The company is conducting a Phase 1/2a dose escalation and expansion study of [212Pb]VMT-α-NET (clinicaltrials.gov identifier NCT05636618) in patients with unresectable or metastatic somatostatin receptor type 2 (SSTR2)-positive neuroendocrine tumors (NETs) who have not received prior radiopharmaceutical therapies (RPT). Initial results, with a data cut-off date of October 31, 2024, were presented at the 2024 North American Neuroendocrine Tumor Society (NANETS) Multidisciplinary NET Medical Symposium in November 2024.

Safety findings from the study indicated no dose-limiting toxicities (DLTs) among patients. No grade 4 or 5 treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) were observed. Two grade 3 adverse events (AEs) – one case of diarrhea and one case of syncope – were reported. Clinical activity has been observed, with eight of nine patients achieving durable disease control. Six of nine patients experienced measurable tumor volume reduction, including one confirmed response per RECIST v1.1 criteria.

VMT01 Program Update

VMT01, a MC1R-targeted radiopharmaceutical therapy (RPT), is being evaluated in a multi-center, open-label dose escalation, dose expansion study (clinicaltrials.gov identifier NCT05655312) in previously treated patients with histologically confirmed melanoma and MC1R-positive imaging scans. Initial results, with a data cut-off date of September 4, 2024, were presented at the 21st International Congress of the Society for Melanoma Research (SMR) in October 2024.

No dose-limiting toxicities were observed, and treatment emergent adverse events (TEAEs) were mostly Grades 1 and 2. One patient experienced an unconfirmed RECIST version 1.1 objective response, and two patients had stable disease at 9 and 11 months from the start of treatment, respectively.

PSV359 Development

Perspective Therapeutics is also developing PSV359, designed to target and deliver 212Pb to tumor sites expressing fibroblast activation protein-α (FAP-α), associated with various solid tumors. An IND was filed in late 2024, and the study could potentially open for enrollment around mid-2025. Preclinical and human imaging results suggest improved target engagement and uptake in tumors with reduced retention in healthy tissues.

PMV Pharmaceuticals Advances Rezatapopt in TP53 Y220C-Mutated Solid Tumors

PMV Pharmaceuticals is focused on precision oncology, particularly targeting the p53 pathway. The company's lead candidate, rezatapopt (PC14586), is a first-in-class investigational therapy for patients with advanced solid tumors harboring a TP53 Y220C mutation.

PYNNACLE Trial Update

The registrational Phase 2 portion of the PYNNACLE clinical trial is evaluating rezatapopt as monotherapy in patients with TP53 Y220C and KRAS wild-type advanced solid tumors. Enrollment is on track, with over 75% of sites activated across the U.S., Europe, and Asia-Pacific. An interim analysis is expected by mid-2025.

Phase 1 data of rezatapopt in advanced ovarian cancer were presented at the 2024 SGO Annual Meeting on Women’s Cancer, showing promising efficacy in heavily pre-treated patients with the TP53 Y220C mutation. Of the 15 efficacy-evaluable patients, seven achieved a confirmed partial response with a seven-month median duration of response and a favorable safety profile.

Companion Diagnostic Development

PMV Pharmaceuticals is collaborating with Foundation Medicine to develop FoundationOne®CDx as a companion diagnostic for rezatapopt. This collaboration aims to identify patients with the TP53 Y220C mutation who are most likely to benefit from rezatapopt therapy.