[212Pb]VMT-alpha-NET for Neuroendocrine Tumors

Overseen By Joy H Zou, R.N.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Radioligand therapy

Disqualifiers: Allergic reactions, Pregnancy, Secondary malignancy, others

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

Compensation: Varies

Number of Visits: 9

Duration: 32 weeks

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, [212Pb]VMT-alpha-NET, designed to treat specific tumors, including gastrointestinal neuroendocrine tumors (GI NET) and pheochromocytoma/paragangliomas (PPGL). The drug targets a specific protein on these tumors and delivers a radioactive agent to kill cancer cells. The trial includes different groups to test varying doses and observe the drug's behavior in the body through imaging. Eligible participants are adults with tumors that have spread and cannot be surgically removed, and who have previously received a specific type of cancer treatment. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new drug.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but it does mention that all other investigational agents should be stopped at least 28 days before receiving the study drug. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that [212Pb]VMT-alpha-NET is promising in terms of safety. Studies have found doses up to 185 MBq to be safe, and researchers are testing even higher doses because they can manage the side effects. Early results suggest that this treatment, which uses a radioactive substance to target and destroy cancer cells, is well-tolerated. Imaging with [203Pb]VMT-alpha-NET, a related study drug, is also considered safe. Although these treatments remain under investigation, the initial safety data is encouraging for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for neuroendocrine tumors, which often include somatostatin analogs or targeted therapies, [212Pb]VMT-alpha-NET introduces a novel approach by incorporating a radioactive element, lead-212, to specifically target tumor cells. This treatment is unique because it leverages targeted alpha-particle therapy, potentially delivering a more precise and potent form of radiation directly to cancer cells, thereby minimizing damage to surrounding healthy tissue. Researchers are excited about these treatments because they offer the possibility of more effective tumor control with potentially fewer side effects, and the use of imaging with [203Pb]VMT-alpha-NET in some trial arms may enhance treatment planning by allowing for better visualization of tumor uptake.

What evidence suggests that this trial's treatments could be effective for neuroendocrine tumors?

Research has shown that [212Pb]VMT-alpha-NET may effectively treat neuroendocrine tumors. This trial will explore various approaches to using [212Pb]VMT-alpha-NET, including escalating doses and determining the maximum tolerated dose (MTD). The drug targets somatostatin receptors, proteins found in large amounts on these tumors. Early studies found that the drug is safe and can stop tumor growth, even at low doses. Lab tests also showed it could slow down and sometimes completely stop tumor growth. These findings suggest that [212Pb]VMT-alpha-NET could be a strong option for treating these challenging cancers. ^{5 6 7 8 9}

Who Is on the Research Team?

Frank I Lin, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults with gastrointestinal neuroendocrine tumors or pheochromocytoma/paragangliomas that have spread and can't be surgically removed. They must have been previously treated with targeted radioligand therapy.

Inclusion Criteria

Must have at least 1 measurable lesion by RECIST 1.1 (phase II only)

My cancer has worsened in the last 3 years as shown by tests or symptoms.

My brain scans show no signs of cancer growth after treatment for brain metastases.

Exclusion Criteria

Uncontrolled intercurrent illness or factors evaluated by medical history and physical exam which would potentially increase the risk of the participant

I have no active secondary cancers except for skin cancer or cervical carcinoma in situ.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to VMT-alpha-NET

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive [212Pb]VMT-alpha-NET in four 8-week cycles, with infusions on the first day of each cycle and monitoring for up to 48 hours post-infusion

32 weeks

4 visits (in-person) per cycle, weekly blood tests

Dosimetry

A subset of participants receive [203Pb]VMT-alpha-NET for imaging and dosimetry studies before the first two cycles

16 weeks

Additional visits for imaging at 4, 24, and 48 hours post-infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment, with visits approximately 30 days post-treatment, every 12 weeks for years 1-3, every 6 months for years 4-6, and annually thereafter

10 years

What Are the Treatments Tested in This Trial?

Interventions

• [212Pb]VMT-alpha-NET

Trial Overview [212Pb]VMT-alpha-NET, a drug combining a protein targeting somatostatin receptors on cancer cells with a radioactive agent to destroy them, is being tested over four 8-week cycles of infusion treatments.

How Is the Trial Designed?

Group I: 3/Arm 3 Experimental Treatment 2 Interventions

\[212Pb\]VMT-alpha-NET at MTD.

Group II: 2/Arm 2 Experimental Treatment 2 Interventions

Escalating doses of \[212Pb\]VMT-alpha-NET.

Group III: 1/Dosimetry Arm 1 Experimental Treatment 3 Interventions

Escalating doses of \[212Pb\]VMT-alpha-NET, imaging with \[203Pb\]VMT-alpha-NET.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

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]

Combining peptide receptor radionuclide therapy (PRRT) with anti-PD1 immunotherapy significantly enhances treatment response in neuroendocrine tumors (NETs), with the most effective approach being to administer PRRT before anti-PD1 therapy.

In a study involving 96 mice with human NET cells, the early PRRT regimen led to the greatest reduction in tumor size and increased T-cell activation, indicating a robust inflammatory response compared to other treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of Peptide Receptor Radiotherapy to Immune Checkpoint Inhibition Therapy Improves Outcomes in Neuroendocrine Tumors. Esfahani, SA., De Aguiar Ferreira, C., Summer, P., et al.[2023]

In a study of 43 patients with advanced gastrointestinal neuroendocrine tumors, (177)Lu-Dotatate peptide receptor radionuclide therapy (Lu-PRRT) demonstrated an 84% disease control rate, with a median response duration of 25 months and a median progression-free survival of 36 months.

Both standard and reduced dosages of Lu-PRRT were found to be safe, as none of the patients experienced side effects, even those at higher risk for kidney or bone marrow toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177 Lu-Dota-octreotate radionuclide therapy of advanced gastrointestinal neuroendocrine tumors: results from a phase II study. Paganelli, G., Sansovini, M., Ambrosetti, A., et al.[2022]

Neuroendocrine neoplasms (NEN), particularly well-differentiated types, can be effectively diagnosed and treated using peptide receptor radionuclide therapy (PRRT) with somatostatin receptor analogues, which have been shown to be a safe and effective treatment option following FDA and EMA approval of 177Lu-DOTATATE.

Current research is focused on enhancing the efficacy of PRRT and minimizing its toxicity through personalized treatment approaches, improved patient selection, and the development of new radiopharmaceuticals, indicating a promising future for NEN management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular imaging Theranostics of Neuroendocrine Tumors. Fortunati, E., Bonazzi, N., Zanoni, L., et al.[2023]

In a study involving 35 patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with Lutathera (177Lu-DOTATATE), the treatment was well tolerated, with most adverse events being low grade.

Among patients who completed all 4 cycles of Lutathera, 22% showed a partial response, 44% had stable disease, and 13% experienced disease progression, indicating Lutathera's potential efficacy in managing GEP-NETs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide receptor radionuclide therapy implementation and results in a predominantly gastrointestinal neuroendocrine tumor population: A two-year experience in a nonuniversity setting. Mejia, A., Vivian, E., Nwogu, C., et al.[2023]

In a patient with advanced midgut neuroendocrine tumor and carcinoid heart disease, the use of 203 Pb-VMT-α-NET showed high uptake in liver metastases, indicating its potential effectiveness for targeted therapy.

The imaging results from 203 Pb-VMT-α-NET were comparable to those from 68 Ga-HA-DOTATATE PET/CT, suggesting that 203 Pb-VMT-α-NET could be a feasible option for therapy in patients who are refractory to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

203 Pb-VMT-α-NET Scintigraphy of a Patient With Neuroendocrine Tumor. Müller, D., Herrmann, H., Schultz, MK., et al.[2023]

A 46-year-old man with rectal neuroendocrine tumors and extensive skeletal metastases was treated with 6 cycles of 225Ac-DOTATATE, showing excellent symptomatic, biochemical, and radiological responses without severe adverse events.

The use of 225Ac-DOTATATE as a first-line treatment offers a promising new strategy for patients with metastatic neuroendocrine tumors who have a high burden of skeletal disease, potentially overcoming the limitations of traditional β-emitter therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpha Before Beta: Exceptional Response to First-Line 225Ac-DOTATATE in a Patient of Metastatic Neuroendocrine Tumor With Extensive Skeletal Involvement. Satapathy, S., Sood, A., Das, CK., 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. 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.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3005

[212Pb]VMT-α-NET therapy in somatostatin receptor 2 ... Conclusions: [212Pb]VMT-α-NET is a well-tolerated, next generation RPT showing signs of clinical activity at early dose-levels in this phase 1/ ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/65/supplement_2/242430

A Phase I/IIa of [212Pb]VMT-ï ¡-NET Targeted Alpha-Particle ... Introduction: Treatment of neuroendocrine tumors with the b-emitter 177Lu-DOTATATE has been shown to prolong progression free survival and ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06479811

Study Details | NCT06479811 | [212Pb]VMT-Alpha-NET in ... Objective: To test a study drug ([212Pb]VMT-Alpha-NET) in people with tumors that have SSTRs. Eligibility: People aged 18 years and older with tumors of the ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12397198/

[203/212Pb]Pb-VMT-α-NET as a novel theranostic agent ... Preclinical evaluations have shown that [212Pb]Pb-VMT-α-NET therapies are effective in slowing tumor growth and resulted in complete durable ...

6. 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 ... 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) ...

7. 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.

8. 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 ...

9. nanets.net nanets.net/abstracts-archive/2024/2018-c37-wahl-preliminary-safety-and-efficacy-data-of-212pb-vmt-net-in-somatostatin-receptor-2-sstr2-expressing-neuroendocrine-tumors-nets/file

Preliminary safety and efficacy data of [212Pb]VMT-α-NET ... This is a first-in-human dose-escalation study to determine the safety, pharmacokinetics, and preliminary efficacy of [212Pb]VMT-α-NET in adult NETs of any ...