Targeted Alpha-Particle Therapy for Neuroendocrine Tumors

([212-Pb]-VMT Trial)

Recruiting at 13 trial locations

Overseen By Markus Puhlmann, MD, MBA

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Perspective Therapeutics

Must be taking: Somatostatin analogues

Must not be taking: PRRT therapies

Disqualifiers: Active malignancy, Pregnancy, Brain metastases, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This study is Phase I/IIa First-in-Human Study of \[212Pb\]VMT-α-NET Targeted Alpha-Particle Therapy for Advanced SSTR2 Positive Neuroendocrine Tumors

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.

What data supports the effectiveness of the treatment [212Pb]VMT-α-NET for neuroendocrine tumors?

Research on similar treatments, like [212Pb]Pb-eSOMA-01, shows promising results for neuroendocrine tumors, with high tumor uptake and effective targeting of cancer cells while sparing healthy tissue. Additionally, other targeted alpha therapies, such as 225Ac-DOTATATE, have shown partial responses in patients with neuroendocrine tumors, suggesting potential effectiveness for [212Pb]VMT-α-NET. ^{1 2 3 4 5}

Is targeted alpha-particle therapy for neuroendocrine tumors safe for humans?

Current studies on targeted alpha-particle therapy, including those using lead-212, suggest it is generally safe in humans, with no significant blood, kidney, or liver toxicity reported. However, more research is needed to fully understand its long-term safety. ^{1 2 3 5 6}

What makes the drug [212Pb]VMT-α-NET unique for treating neuroendocrine tumors?

The drug [212Pb]VMT-α-NET is unique because it uses targeted alpha-particle therapy, which involves alpha particles that deliver high energy directly to tumor cells, potentially leading to more effective tumor cell killing while sparing surrounding healthy tissue. This approach is different from traditional treatments that use beta particles, offering a novel option for patients, especially those who have not responded to other therapies. ^{1 2 3 4 7}

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• [212Pb]VMT-α-NET (Radioisotope Therapy)

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.

Participant Groups

Group I: Dose Expansion with RPh2D Experimental Treatment 1 Intervention

Up to 120 patients with NET

Group II: Dose Escalation Experimental Treatment 1 Intervention

Dose Escalation to determine MTD/MFD in up to 160 patients receiving up to 4 administrations of \[212Pb\]VMT-α-NET approximately 8 weeks apart. A dosimetry sub-study utilizing \[203Pb\]VMT-α-NET has been incorporated into the study.

Who Is Running the Clinical Trial?

Perspective Therapeutics

Lead Sponsor

Trials

6

Recruited

710+

Viewpoint Molecular Targeting

Lead Sponsor

Trials

4

Recruited

570+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

[212Pb]Pb-eSOMA-01: A Promising Radioligand for Targeted Alpha Therapy of Neuroendocrine Tumors. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Targeted alpha-particle therapy in neuroendocrine neoplasms: A systematic review. [2022]

3. Turkey pubmed.ncbi.nlm.nih.gov

Initial Findings on the Use of [225Ac]Ac-DOTATATE Therapy as a Theranostic Application in Patients with Neuroendocrine Tumors. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Gastro-Enteric-Pancreatic Neuroendocrine Tumor Treatment: Actinium-225-DOTATATE and Combined Therapies. [2023]

5. Germany 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. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Targeted Alpha-Particle Therapy: A Review of Current Trials. [2023]

7. Turkey 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. [2022]