Targeted Alpha-Particle Therapy for Neuroendocrine Tumors

([212-Pb]-VMT Trial)

Recruiting at 18 trial locations

Overseen By ClinicalTrials at Perspectivetherapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Perspective Therapeutics

Must be taking: Somatostatin analogues

Must not be taking: PRRT therapies

Disqualifiers: Active malignancy, Pregnancy, Brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

260 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called [212Pb]VMT-α-NET, a targeted alpha-particle therapy, for individuals with advanced neuroendocrine tumors positive for the SSTR2 receptor. The trial aims to determine the appropriate dose and evaluate the treatment's safety and early effectiveness. It seeks participants whose tumors are inoperable or have metastasized and have shown growth in the past year. This study is suitable for those who have not received certain prior treatments, such as radionuclide therapy, and can temporarily pause their SSA therapy. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial allows the use of somatostatin analogues (SSAs) if you have a functional tumor and have shown disease progression on SSA therapy. Long-acting SSAs should be stopped 30 days before certain scans, and short-acting SSAs should be stopped 24 hours before. Other systemic anticancer therapies must be stopped 30 days before joining the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that [212Pb]VMT-α-NET, a targeted therapy using alpha particles, was safe in earlier studies. For doses up to 185 MBq (a unit measuring radioactivity), the treatment was considered safe. A safety committee approved increasing the dose to 277.5 MBq, indicating that the treatment is well-tolerated at these levels.

Experts have observed that any side effects can be managed, meaning they can be controlled or treated effectively. This therapy specifically targets somatostatin receptors, often found in neuroendocrine tumors, helping to reduce effects on healthy tissue.

Overall, early evidence suggests that [212Pb]VMT-α-NET is safe enough to continue studying in clinical trials. Anyone considering joining a clinical trial should discuss the potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for neuroendocrine tumors, which often rely on surgery, chemotherapy, or radiation therapy, [212Pb]VMT-α-NET is a novel approach that uses targeted alpha-particle therapy. This treatment stands out because it delivers alpha particles directly to the tumor cells, potentially sparing healthy tissues from damage. Researchers are excited about this treatment because it introduces a new mechanism of action by utilizing lead-212, an alpha-emitting radioisotope, which can effectively kill cancer cells with high precision. This targeted approach could offer a more effective and safer option compared to traditional therapies.

What evidence suggests that [212Pb]VMT-α-NET might be an effective treatment for neuroendocrine tumors?

Research has shown that [212Pb]VMT-α-NET holds promise for treating neuroendocrine tumors. Early results suggest it can slow or halt cancer growth. The trial includes a Dose Finding arm to determine the optimal biological dose (OBD) and potential recommended phase 2 dose (RP2D) in up to 200 patients. Additionally, a Dose Expansion arm will further assess safety and preliminary efficacy in up to 60 subjects. This treatment targets specific receptors on tumor cells, using a radioactive substance to attack and destroy them. Previous studies have demonstrated its ability to reduce the size of some tumors. Overall, the treatment shows potential for significant benefits in patients with these tumors. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with advanced neuroendocrine tumors that show SSTR2 positivity on specific PET scans. Participants must have measurable disease progression, an ECOG Performance Status of 0-2, and a life expectancy over 3 months. Those with HIV can join if they meet certain criteria. It's not for pregnant women, those with severe recent nausea/vomiting or diarrhea, known hypersensitivity to related drugs, active secondary cancers (except stable brain metastases), or inadequate organ function.

Inclusion Criteria

My cancer has grown or spread in the last year, as shown by scans.

You are expected to live for more than 3 months.

I can take care of myself and am up and about more than half of the day.

Exclusion Criteria

I had major surgery more than 30 days ago.

Treatment with another investigational drug product (therapeutic IND agents) within 30 days of anticipated treatment

Known medical condition which would make this protocol unreasonably hazardous for the subject

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Radioactivity dose escalation period testing up to 4 escalating dose cohorts with doses administered approximately 8 weeks apart

32 weeks

4 visits (in-person)

Dose Expansion

Recommended expansion dose(s) determined following analysis of observed DLTs, AEs, and efficacy signals

Variable, up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

42 days

What Are the Treatments Tested in This Trial?

Interventions

• [212Pb]VMT-α-NET

Trial Overview [212Pb]VMT-α-NET Targeted Alpha-Particle Therapy is being tested in this Phase I/IIa study for its effectiveness against advanced SSTR2 positive neuroendocrine tumors. The therapy aims to deliver radiation directly to the cancer cells while sparing healthy tissue.

How Is the Trial Designed?

Group I: Dose Finding Experimental Treatment 2 Interventions

Dose Finding to determine OBD and potential RP2D in up to 200 patients receiving up to 4 administrations of \[212Pb\]VMT-α-NET approximately 8 weeks apart. A dosimetry sub-study utilizing \[203Pb\]VMT-α-NET is incorporated into the study.

Group II: Dose Expansion Experimental Treatment 2 Interventions

Dose with up to 60 subjects at RP2D for further assessment of safety and preliminary efficacy.

Who Is Running the Clinical Trial?

Perspective Therapeutics

Lead Sponsor

Trials

6

Recruited

710+

Viewpoint Molecular Targeting

Lead Sponsor

Trials

4

Recruited

570+

Published Research Related to This Trial

Targeted alpha emitters like 225actinium, 212lead, and 211astatine are being actively studied in clinical trials for various cancers, with at least one phase III trial currently recruiting participants for neuroendocrine cancers.

While targeted alpha therapies show great promise in treating advanced cancers, challenges such as establishing reliable supply chains and understanding the relationship between dosage and treatment outcomes need to be addressed for successful clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Alpha-Particle Therapy: A Review of Current Trials. Jang, A., Kendi, AT., Johnson, GB., et al.[2023]

In a study of 11 patients with grade 1/2 metastatic neuroendocrine tumors treated with [225Ac]Ac-DOTATATE, the therapy demonstrated a high disease control rate of 89%, with 44.4% of patients showing a partial response and 44.4% having stable disease.

The treatment was found to be stable and safe, with only mild toxicities reported (grade 2 renal and hematotoxicity), and a median progression-free survival of 12 months, indicating its potential effectiveness for patients who were refractory to previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Findings on the Use of [225Ac]Ac-DOTATATE Therapy as a Theranostic Application in Patients with Neuroendocrine Tumors. Demirci, E., Alan Selçuk, N., Beydağı, G., et al.[2023]

Peptide receptor radionuclide therapy (PRRT) is a promising treatment for neuroendocrine tumors (NETs), particularly in metastatic cases, contributing to improved progression-free and overall survival.

In a case study, a patient with over 50 abdominal lesions experienced almost complete disappearance of these lesions after a single dose of 225Ac-DOTATATE, an alpha particle-emitting radionuclide, highlighting its potential high efficacy compared to traditional beta-emitting radionuclides.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Almost Complete Response with a Single Administration 225Ac-DOTATATE in a Patient with a Metastatic Neuroendocrine Tumor of Unknown Primary. Alan Selçuk, N., Demirci, E., Ocak, M., et al.[2022]

Targeted alpha-particle therapy (TAT) using radiopharmaceuticals like 225Ac-DOTATATE and 213Bi-DOTATOC shows promise in treating metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), with evidence of partial responses observed in the reviewed studies.

These therapies appear to have a favorable safety profile, as they did not show significant hematological, renal, or hepatotoxicity, suggesting they could be viable options after the failure of 177Lu-DOTATATE therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted alpha-particle therapy in neuroendocrine neoplasms: A systematic review. Koh, TT., Bezak, E., Chan, D., et al.[2022]

Actinium-225-DOTATATE, a targeted alpha therapy, shows promise in improving treatment outcomes for advanced gastro-entero-pancreatic neuroendocrine tumors due to its higher efficiency in killing tumor cells compared to lutetium-177-DOTATATE.

This therapy is considered safe because the alpha particles have a shorter path length, which minimizes damage to surrounding healthy tissue and leads to fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastro-Enteric-Pancreatic Neuroendocrine Tumor Treatment: Actinium-225-DOTATATE and Combined Therapies. Satapathy, S., Chandekar, KR., Bal, C.[2023]

Targeted alpha therapy (TAT) using lead-212 (212Pb) shows promise for treating neuroendocrine tumors (NETs), with the study identifying [212Pb]Pb-eSOMA-01 as a leading candidate based on its high tumor uptake and low kidney absorption in tests with tumor-bearing mice.

The ligands developed for this therapy demonstrated high radiochemical yields and stability, with [212Pb]Pb-eSOMA-01 achieving the highest absorbed dose in tumors (35.49 Gy/MBq) while minimizing exposure to healthy tissues, indicating a potential for safer and more effective treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[212Pb]Pb-eSOMA-01: A Promising Radioligand for Targeted Alpha Therapy of Neuroendocrine Tumors. Chapeau, D., Koustoulidou, S., Handula, M., et al.[2023]

In a study of 32 patients with advanced metastatic GEP-NETs who were refractory to 177Lu-DOTATATE therapy, 225Ac-DOTATATE targeted alpha therapy showed promising efficacy, with 15 patients achieving partial remission and no documented disease progression during a median follow-up of 8 months.

The therapy also resulted in a significant decrease in plasma chromogranin levels, indicating a biochemical response, and suggests that 225Ac-DOTATATE could be a valuable treatment option for patients who have exhausted other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Broadening horizons with 225Ac-DOTATATE targeted alpha therapy for gastroenteropancreatic neuroendocrine tumour patients stable or refractory to 177Lu-DOTATATE PRRT: first clinical experience on the efficacy and safety. Ballal, S., Yadav, MP., Bal, C., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06479811

Study Details | NCT06479811 | [212Pb]VMT-Alpha-NET in ... Researchers want to know if drug treatments that target SSTRs can help shrink these types of tumors. Objective: To test a study drug ([212Pb]VMT-Alpha-NET) in ...

2. perspectivetherapeutics.com perspectivetherapeutics.com/pr/perspective-therapeutics-presents-updated-interim-data-from-its-ongoing-phase-12a-clinical-trial-of-212pbvmtnet-at-the-esmo-congress-2025

Press Release Perspective Therapeutics Presents Updated Interim Data from its Ongoing Phase 1/2a Clinical Trial of [212Pb]VMT-α-NET at the ESMO Congress 2025.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.668

Interim safety and efficacy data of [ 212 Pb]VMT-α-NET in ... Early efficacy results demonstrate encouraging progression-free survival. Clinical trial information: NCT05636618. This is an ASCO Meeting ...

4. sanofi.com sanofi.com/en/media-room/press-releases/2025/2025-10-08-05-00-00-3163053

Press Release: AlphaMedixTM (212Pb-DOTAMTATE) ... AlphaMedixTM (212Pb-DOTAMTATE) achieved all primary efficacy endpoints in phase 2 study, demonstrating clinically meaningful benefits in ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06427798

NCT06427798 | Somatostatin-Receptors ( ... To test a drug ([212Pb]VMT-alpha-NET) in people with GI NET or PPGL. The drug has 2 components: a protein to bind to SSTR and a radioactive agent to kill the ...

6. pharmacytimes.com pharmacytimes.com/view/expert-discusses-early-safety-and-tolerability-findings-for-vmt---net-in-neuroendocrine-tumors-esmo-2025

Expert Discusses Early Safety and Tolerability Findings for ... Oncologist Thor Halfdanarson reviews dose-finding data for the targeted α radioligand therapy [^212Pb]VMT- α-NET, highlighting manageable ...

7. jnm.snmjournals.org jnm.snmjournals.org/content/66/supplement_1/251949

[212Pb]Pb-VMT-α-NET dosimetry in patients with advanced ... Introduction: [212Pb]Pb-VMT-α-NET is a novel alpha-emitting radiopharmaceutical therapy (RPT) developed for the treatment of somatostatin ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06148636

NCT06148636 | A Safety Study of 212Pb-VMT-alpha-NET ... This is a safety study to determine the recommended dose to test in clinical trials. The study involves two treatments with 212Pb (212-lead) VMT-α-NET.