VMT-𝛼-NET / Perspective Therap, Lantheus - LARVOL DELTA

Perspective Therapeutics Provides Recent Business Highlights and Reports Full Year 2024 Results (GlobeNewswire) - "Company-sponsored Phase 1/2a trial of [212Pb]VMT-α-NET....Since the start of 2025 through the end of February 2025, an incremental 12 patients have been dosed. Thus, a total of 30 patients have received treatment in Cohort 2 as of February 28, 2025. Cohort 2 remains open for recruitment. By 3Q and 4Q 2025, all patients enrolled through February 28, 2025 will have had the opportunity for at least 32 weeks of follow-up after their initial doses, sufficient time to receive at least one scan after their full treatment (up to four doses every eight weeks), if they receive all four doses of treatment per protocol. We plan to submit to scientific congresses updates on patients dosed to date who have had the opportunity to receive at least one scan after their full treatment, in the second half of 2025."

Trial status • Neuroendocrine Carcinoma

Nuclear medicine and perspective thoughts in the diagnosis and treatment of pheochromocytoma and paraganglioma. (PubMed, J Neuroendocrinol) - "It also provides insight into the use of proliferating cell nuclear antigen (PCNA) inhibitors in combination with therapeutics in aggressive/metastatic PPGL. Through a comprehensive review of the latest developments and clinical practice, this review aims to guide healthcare professionals in improving the diagnostic accuracy and therapeutic efficacy of PPGL."

Journal • Review • CNS Tumor • Endocrine Cancer • Oncology • Solid Tumor • PCNA

Somatostatin-Receptors (SSTR)-Agonist [212Pb]VMT-alpha-NET in Metastatic or Inoperable SSTR+ Gastrointestinal Neuroendocrine Tumor and Pheochromocytoma/Paraganglioma Previously Treated With Systemic Targeted Radioligand Therapy (clinicaltrials.gov) - P1/2 | N=66 | Recruiting | Sponsor: National Cancer Institute (NCI) | Suspended ➔ Recruiting

Enrollment open • CNS Tumor • Endocrine Cancer • Gastrointestinal Disorder • Neuroendocrine Tumor • Oncology • Solid Tumor

Somatostatin-Receptors (SSTR)-Agonist [212Pb]VMT-alpha-NET in Metastatic or Inoperable SSTR+ Gastrointestinal Neuroendocrine Tumor and Pheochromocytoma/Paraganglioma Previously Treated With Systemic Targeted Radioligand Therapy (clinicaltrials.gov) - P1/2 | N=66 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Tumor • Endocrine Cancer • Gastrointestinal Disorder • Neuroendocrine Tumor • Oncology • Solid Tumor

Somatostatin-Receptors (SSTR)-Agonist [212Pb]VMT-alpha-NET in Metastatic or Inoperable SSTR+ Gastrointestinal Neuroendocrine Tumor and Pheochromocytoma/Paraganglioma Previously Treated With Systemic Targeted Radioligand Therapy (clinicaltrials.gov) - P1/2 | N=66 | Suspended | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Suspended

Trial suspension • CNS Tumor • Endocrine Cancer • Gastrointestinal Disorder • Neuroendocrine Tumor • Oncology • Solid Tumor

Interim safety and efficacy data of [212 Pb]VMT-α-NET in somatostatin receptor 2 (SSTR2) expressing neuroendocrine tumors (NETs). (ASCO-GI 2025) - P1/2 | "No patient may have received prior 177Lu-DOTATATE or PRRT...Subjects in cohorts 1 and 2 underwent dosimetry evaluations using the therapeutic surrogate [203Pb]VMT-a-NET... [212Pb]VMT-α-NET is safe up to 185 MBq (5 mCi) dose level, and the SMC supported dose escalate to cohort 3 at 277.5 MBq (7.5 mCi) following a mandated FDA review in fall. Cohort 2 remains open for dose level expansion. Early efficacy results demonstrate encouraging progression-free survival."

Clinical • Gastrointestinal Cancer • Oncology • Solid Tumor • SSTR • SSTR2

Lead-it-EAZY! GMP-compliant production of [212Pb]Pb-PSC-PEG2-TOC. (PubMed, EJNMMI Radiopharm Chem) - "The Lead-it-EAZY process performed stable and robust over ten radiosyntheses and yielded sterile [212Pb]Pb-VMT-α-NET in high purity for patient application. By changing the precursor this process could easily be adapted to other 212Pb-radiopharmaceuticals."

Journal • Nephrology • Renal Disease

Preliminary safety and efficacy data of [212Pb]VMT-α-NET in somatostatin receptor 2 (SSTR2) expressing neuroendocrine tumors (NETs) (NANETS 2024) - P1/2 | "BACKGROUND Despite the introduction of Lutathera, there remains an unmet medical need for new front-line therapies for advanced NETs...CONCLUSIONS [212Pb]VMT-α-NET is safe up to 185 MBq (5 mCi) dose level, and the SMC supported dose escalate to cohort 3 at 277.5 MBq (7.5 mCi) following a mandatory FDA review in fall. Cohort 2 remains open for dose level expansion."

Clinical • Alopecia • CNS Tumor • Endocrine Cancer • Fatigue • Immunology • Infectious Disease • Lung Cancer • Nephrology • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • SSTR • SSTR2

Perspective Therapeutics to Pursue Dose Escalation of [212Pb]VMT-α-NET in its Ongoing Phase 1/2a Clinical Trial Based on Data Presented at the 2024 North American Neuroendocrine Tumor Society (NANETS) Multidisciplinary NET Medical Symposium (GlobeNewswire) - P1/2a | N=280 | NCT05636618 | Sponsor: Perspective Therapeutics | "Safety findings: No dose limiting toxicities (DLTs) were observed among any patients. No grade 4 or 5 treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) were observed....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 µCi/kg per dose, then received the remaining two doses at a reduced activity level of 42.4 µCi/kg. One patient was deemed to have progressive disease after one dose under RECIST v1.1, by unambiguous progression of non-target lesions."

P1/2 data • Neuroendocrine Tumor

Perspective Therapeutics to Discuss Data on [212Pb]VMT-α-NET Presented at the 2024 North American Neuroendocrine Tumor Society (NANETS) Multidisciplinary NET Medical Symposium on November 21, 2024 (GlobeNewswire) - "Perspective Therapeutics, Inc...released details regarding the upcoming presentation of initial results from the Company-sponsored Phase 1/2a trial of [212Pb]VMT-α-NET at the 2024 North American Neuroendocrine Tumor Society (NANETS) Multidisciplinary NET Medical Symposium taking place November 21-23, 2024 in Chicago....Perspective will host a conference call on Thursday, November 21, 2024 at 8:00 am ET to discuss data to be presented at the NANETS symposium."

P1/2 data • Neuroendocrine Tumor

Perspective Therapeutics Presents Updates at the 37th Annual Congress of the European Association of Nuclear Medicine (GlobeNewswire) - P=NA | N=NA | "The aim of this analysis was to assess the biodistribution and image-guided dosimetric estimates of [²¹²Pb]Pb-VMT-α-NET peptide used for targeted alpha therapy in patients with GEP-NETs....The results demonstrated that the SPECT/CT imaging with [²¹²Pb]Pb-VMT-α-NET showed prompt tumor accumulation, high tumor retention, and rapid renal excretion in all patients. Overall, the findings suggest that post-treatment imaging of [²¹²Pb]Pb-VMT-α-NET is feasible and can serve as a valuable tool to evaluate and monitor patients through a full course of treatment."

Clinical data • Gastrointestinal Cancer • Neuroendocrine Tumor • Pancreatic Cancer

Perspective Therapeutics Presents Updates at the 37th Annual Congress of the European Association of Nuclear Medicine (GlobeNewswire) - P1 | N=20 | NCT05111509 | "This is an investigator led, exploratory first-in-human use of [²¹²Pb]Pb-VMT-α-NET in adult patients with unresectable or metastatic SSTR2-positive neuroendocrine tumors ('NETs') and medullary thyroid carcinomas in a compassionate setting in India....Treatment was well-tolerated with a modest and manageable adverse effect profile. Confirmed tumor responses per RECIST 1.1 were observed in six of ten GEP-NETs patients. The investigator concluded that the toxicity profile suggests the potential for dose escalation to achieve optimal treatment responses. Long term survival data will mature with continued follow-up."

P1 data • Gastrointestinal Cancer • Neuroendocrine Tumor • Pancreatic Cancer • Thyroid Gland Carcinoma

Perspective Therapeutics Presents Updates at the 37th Annual Congress of the European Association of Nuclear Medicine (GlobeNewswire) - "The purpose of this study was to develop an understanding of how the MA of SSTR2 agonist [203Pb]Pb-VMT-α-NET (an imaging surrogate for [212Pb]Pb-VMT-α-NET) impacts its biodistribution in tumor-free and SSTR2+ tumor bearing mice. Overall findings of the study demonstrated that the MA of [203Pb]Pb-VMT-α-NET impacts the uptake in low-SSTR2 expressing organs. Results suggest that a 'sweet spot' of total injected mass of [203Pb]Pb-VMT-α-NET (<0.5 nmol) can be found in which the tumor to normal tissue ratios can be found."

Preclinical • Neuroendocrine Tumor

Perspective Therapeutics Begins Shipping Investigational Products from State-of-the-Art Radiopharmaceutical Manufacturing Facility in Somerset, New Jersey (GlobeNewswire) - "Perspective Therapeutics, Inc...is celebrating the first shipment and patient dosing from its second manufacturing facility for the production of its 203Pb- and 212Pb-labeled radiopharmaceuticals. Located in Somerset, New Jersey, this facility is now operational to supply investigational products to support VMT-α-NET clinical studies, in addition to the Coralville, Iowa facility which has been producing the Company’s investigational products for over 15 months."

Commercial • Oncology

Impact of molar activity on [203Pb]Pb-VMT-α-NET biodistribution profile in mice bearing neuroendocrine tumor xenograft (EANM 2024) - "The MA of [203Pb]VMT-α-NET impacts the uptake in low-SSTR2 expressing organs. Results suggest that a "sweet spot" of total injected mass of [203Pb]VMT-α-NET (<0.5 nmol) can be found in which tumor to normal ratio can be optimized. These findings provide a potential new strategy that could be used to optimize this aspect of RPT."

Preclinical • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR2

Image guided evaluation of 212Pb-VMT-α-NET in metastatic Neuroendocrine tumors: Bio distribution and Dosimetry (EANM 2024) - "The SPECT/CT imaging with 212Pb-VMT-α-NET showed prompt tumor accumulation, high tumor retention, and rapid renal excretion. Image guided dosimetry of 212Pb-peptide for targeted alpha therapy seems to be an accurate and a straight forward option for dose calculation, however, the dosimetry estimate for clinical translation requires a larger study."

Metastases • Endocrine Cancer • Hematological Malignancies • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR

Interim results of 212Pb-VMT-α-NET Targeted Alpha Therapy in Metastatic Gastro-entero-pancreatic Neuroendocrine Tumors: First In-human Clinical Results on Safety and Efficacy (EANM 2024) - "The objective of this study was to investigate the interim results on safety and efficacy of 212Pb-VMT-alpha-NET therapy (TAT) in patients with advanced, progressive, 177Lu-DOTATATE refractory, somatostatin receptor (SSTR) positive, metastatic gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). The interim results of the 212Pb-VMT-α-NET therapy seems to be encouraging following favourable clinical as well as radiological response in seventy percent of patients. Also, the treatment appears to be safe, with minimal and transient side effects. However, the long-term survival data will emerge with extended follow-up."

Clinical • Metastases • P1 data • Alopecia • Endocrine Cancer • Fatigue • Hematological Disorders • Hepatology • Immunology • Nephrology • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Renal Disease • Solid Tumor • SSTR

212-Pb-VMT: Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Neuroendocrine Tumors (clinicaltrials.gov) - P1/2 | N=280 | Recruiting | Sponsor: Perspective Therapeutics | N=52 ➔ 280 | Trial completion date: Jan 2028 ➔ Dec 2029 | Trial primary completion date: Sep 2026 ➔ Nov 2029

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Carcinoid Tumor • CNS Tumor • Endocrine Cancer • Glioma • Hepatology • Lung Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Small Cell Lung Cancer • Solid Tumor • CD4 • SSTR • SSTR2

Lead-203 VMT-α-Neuroendocrine Tumor Scintigraphy: A Promising Theranostics Agent. (PubMed, Indian J Nucl Med) - "As Pb-203 presents an accurate diagnostic surrogate to Pb-212, imaging with Pb-203-labelled peptides can be an important prerequisite to assess the feasibility of TAT with Pb-212-labelled agents. Here, we present the imaging data of a patient with metastatic NET with Pb-203 VMT-α-NET, a somatostatin receptor targeting agent, and demonstrate the matching distribution of Pb-203 VMT-α-NET with Ga-68 DOTANOC."

Journal • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR

[212Pb]VMT-Alpha-NET in Metastatic or Inoperable Somatostatin-Receptor Positive Gastrointestinal Neuroendocrine Tumors, Pheochromocytoma/Paragangliomas, Small Cell Lung, Renal Cell, and Head and Neck Cancers (clinicaltrials.gov) - P1 | N=120 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

Metastases • New P1 trial • CNS Tumor • Endocrine Cancer • Gastrointestinal Disorder • Genito-urinary Cancer • Head and Neck Cancer • Kidney Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Renal Cell Carcinoma • Small Cell Lung Cancer • Solid Tumor

A Phase I/IIa of [212Pb]VMT--NET Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Neuroendocrine Tumors (SNMMI 2024) - P1/2 | "Purpose/Background: Treatment of neuroendocrine tumors with the b-emitter 177Lu-DOTATATE has been shown to prolong progression free survival and is currently an approved treatment for patients with progressive somatostatin-expressing (SSTR+) grade 1 and grade 2 gastroenteropancreatic NETs...We developed [212Pb]VMT-a-NET, a lead-specific chelator conjugated to the SSTR-targeting peptide octreotide via a polyethylene linker... N/A"

Metastases • P1/2 data • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR • SSTR2

A Phase I/IIa of [212Pb]VMT--NET Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Neuroendocrine Tumors (SNMMI 2024) - P1/2 | "Purpose/Background: Treatment of neuroendocrine tumors with the b-emitter 177Lu-DOTATATE has been shown to prolong progression free survival and is currently an approved treatment for patients with progressive somatostatin-expressing (SSTR+) grade 1 and grade 2 gastroenteropancreatic NETs...We developed [212Pb]VMT-a-NET, a lead-specific chelator conjugated to the SSTR-targeting peptide octreotide via a polyethylene linker... N/A"

Metastases • P1/2 data • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR • SSTR2

A Phase I/IIa of [212Pb]VMT--NET Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Neuroendocrine Tumors (SNMMI 2024) - P1/2 | "Purpose/Background: Treatment of neuroendocrine tumors with the b-emitter 177Lu-DOTATATE has been shown to prolong progression free survival and is currently an approved treatment for patients with progressive somatostatin-expressing (SSTR+) grade 1 and grade 2 gastroenteropancreatic NETs...We developed [212Pb]VMT-a-NET, a lead-specific chelator conjugated to the SSTR-targeting peptide octreotide via a polyethylene linker... N/A"

Metastases • P1/2 data • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR • SSTR2

A Phase I/IIa of [212Pb]VMT--NET Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Neuroendocrine Tumors (SNMMI 2024) - P1/2 | "Purpose/Background: Treatment of neuroendocrine tumors with the b-emitter 177Lu-DOTATATE has been shown to prolong progression free survival and is currently an approved treatment for patients with progressive somatostatin-expressing (SSTR+) grade 1 and grade 2 gastroenteropancreatic NETs...We developed [212Pb]VMT-a-NET, a lead-specific chelator conjugated to the SSTR-targeting peptide octreotide via a polyethylene linker... N/A"

Metastases • P1/2 data • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • SSTR • SSTR2

212Pb-VMT-α-NET α-PRRT planning based on 203Pb-VMT-α-NET predictive dosimetry (SNMMI 2024) - P1 | "To our knowledge, this work is the first report of using 203Pb-based predictive dosimetry for personalized therapy with any 212Pb-based radiopharmaceutical in humans. We report initial dosimetry results for 203/212Pb-VMT-α-NET, and initial treatments based upon personalized dosimetry."

Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor