Targeted Alpha-Particle Therapy for Melanoma

Recruiting at 16 trial locations

Overseen By ClinicalTrials at Perspectivetherapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Perspective Therapeutics

Must not be taking: Corticosteroids, Immunosuppressants, Herbal supplements, others

Disqualifiers: Active secondary malignancy, Autoimmune disease, Hepatitis, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

300 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]VMT01, a targeted alpha-particle therapy, for individuals with advanced melanoma that cannot be surgically removed. Researchers aim to determine the safety and effectiveness of this therapy, both alone and in combination with another medicine, nivolumab. The trial includes several stages to identify the optimal dose and evaluate the treatment's efficacy. Individuals with melanoma that has spread or recurred after other treatments may be suitable for this study, particularly if their melanoma exhibits a specific marker (MC1R) and they can remain still for imaging tests. As a Phase 1 trial, this study focuses on understanding the treatment's effects 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 requires a washout period (time without taking certain medications) for those on prior intravenous or oral therapies. You must stop intravenous therapies for 21 days and oral therapies for 7 days before starting the trial treatment.

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

Research has shown that [212Pb]VMT01, a new treatment for melanoma, has a promising safety record in early studies. These studies found that patients tolerated the treatment well, without severe side effects that would prevent the use of higher doses.

When combined with nivolumab, a drug already used for some cancers, [212Pb]VMT01 also demonstrated a manageable safety profile. This combination did not cause any unexpected safety issues, suggesting it could be a viable option for patients.

Overall, the safety results so far are positive, but these findings come from early research stages. Prospective trial participants should discuss potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the investigational treatment [212Pb]VMT01 for melanoma because it utilizes targeted alpha-particle therapy, which offers a unique and precise approach to attacking cancer cells. Unlike traditional treatments like chemotherapy and immunotherapy, which can affect both cancerous and healthy cells, [212Pb]VMT01 specifically targets the tumor, minimizing damage to surrounding tissues. Additionally, this therapy is combined with the use of [203Pb]VMT01 for dosimetry, allowing researchers to optimize the dose delivery and improve treatment outcomes. By using this targeted mechanism, [212Pb]VMT01 has the potential to be more effective and less toxic than existing treatment options.

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

Research has shown that [212Pb]VMT01, a treatment under study in this trial, has potential for treating melanoma by delivering radioactive particles directly to cancer cells. This method aims to destroy cancer cells, leading to noticeable improvements and longer periods without disease progression. In this trial, some participants will receive [212Pb]VMT01 alone, while others will receive it with nivolumab, a drug that boosts the immune system to fight cancer. Studies indicate that this combination results in a strong anti-cancer effect. Specifically, patients receiving this combination therapy have experienced longer periods without disease progression, suggesting that the two treatments work well together. Early evidence suggests this combination might improve treatment outcomes for melanoma. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

Adults over 18 with advanced melanoma that's spread or can't be removed by surgery, who've had at least one prior treatment fail. They must have a tumor visible on specific scans, be able to lie still for imaging, and not be pregnant or breastfeeding. Men and women must agree to use effective contraception.

Inclusion Criteria

My organs are functioning well.

I have completed a wash-out period after my last cancer treatment before starting [212Pb]VMT01.

You are expected to live for at least 3 more months.

Exclusion Criteria

Treatment with another investigational drug product (therapeutic IND agents) within the last 30 days

I do not require immediate treatment for brain metastasis.

Existence of any medical or social issues likely to interfere with study conductor that may cause increased risk to the subject or to others, e.g., lack of ability to follow radiation safety precautions

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Monotherapy Dose-Escalation

[212Pb]VMT01 is administered alone in escalating doses to determine the Maximum Tolerated Dose (MTD), Maximum Feasible Dose (MFD), and potential recommended Phase 2 doses (RP2Ds)

Approximately 8 weeks per dose, up to 3 doses

Combination-Therapy Dose-Escalation

[212Pb]VMT01 and Nivolumab are administered in escalating doses to determine MTD, MFD, and RP2Ds

Approximately 8 weeks per dose, up to 3 doses

Dose Expansion

Subjects are enrolled in monotherapy and combination-therapy expansion cohorts based on the identified MTD, MFD, and RP2D for further clinical development

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• [212Pb]VMT01

Trial Overview [212Pb]VMT01 is being tested for safety and effectiveness in treating advanced melanoma. It's an alpha-particle therapy targeting MC1R receptors on cancer cells. This trial will include patients whose tumors absorb a related compound seen in special imaging tests.

How Is the Trial Designed?

Group I: Monotherapy-Dose Finding Experimental Treatment 2 Interventions

Enrolled subjects will be treated with \[212Pb\]VMT01 to determine optimal biological dose (OBD). A dosimetry sub-set utilizing \[203Pb\]VMT01 has been incorporated.

Group II: Monotherapy - Dose Expansion Experimental Treatment 2 Interventions

Subjects will be enrolled at previously identified recommended phase 2 dose (RP2D) for confirmation of the RP2D and regimen for the Phase 2 dose-expansion cohort. A dosimetry sub-set utilizing \[203Pb\]VMT01 has been incorporated.

Group III: Combination Therapy-Dose Finding Experimental Treatment 3 Interventions

Enrolled subjects will be treated with \[212Pb\]VMT01 in combination with nivolumab to determine OBD. A dosimetry sub-set utilizing \[203Pb\]VMT01 has been incorporated.

Group IV: Combination Therapy - Dose Expansion Experimental Treatment 3 Interventions

Subjects will be enrolled at previously identified RP2D for its confirmation and verification of regimen for the Phase 2 dose-expansion cohort. A dosimetry sub-set utilizing \[203Pb\]VMT01 has been incorporated.

[212Pb]VMT01 is already approved in United States for the following indications:

Approved in United States as VMT01 for:

• Unresectable and metastatic melanoma

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

The study evaluated a melanoma-targeting peptide conjugated with an alpha-particle-emitting radionuclide in a mouse model, showing that this treatment significantly extended survival times in melanoma-bearing mice, with some achieving complete remission.

Mice treated with the highest dose of the radionuclide (200 muCi) had a mean survival of 49.8 days compared to 14.6 days for the placebo group, indicating the potential efficacy of this targeted therapy in overcoming radiation resistance in tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melanoma therapy via peptide-targeted {alpha}-radiation. Miao, Y., Hylarides, M., Fisher, DR., et al.[2010]

Targeted alpha particle therapy (TAT) offers significant therapeutic advantages due to the short and highly ionizing path of alpha particles, which can enhance the efficacy of cancer treatment compared to traditional radiotherapy.

The review highlights ongoing and completed clinical trials, indicating that TAT is a promising area of research with potential for future developments in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Alpha Therapy: Progress in Radionuclide Production, Radiochemistry, and Applications. Nelson, BJB., Andersson, JD., Wuest, F.[2021]

Targeted alpha-particle therapy (TAT) using a 213Bi-anti-human-PD-L1 monoclonal antibody significantly delayed tumor growth and improved survival in a human melanoma xenograft model, indicating its potential as an effective treatment for melanoma.

The treatment showed specific targeting of PD-L1 positive tumors with minimal toxicity, as it did not harm red blood cells, bone marrow, liver, or kidney, although a slight decrease in platelets was noted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-Tumor Efficacy of PD-L1 Targeted Alpha-Particle Therapy in a Human Melanoma Xenograft Model. Capitao, M., Perrin, J., Simon, S., et al.[2021]

In a Phase I study involving 38 patients with stage IV metastatic melanoma, targeted α-therapy using the α-immunoconjugate (213)Bi-cDTPA-9.2.27 showed a 10% objective partial response rate and 40% stable disease at 8 weeks, indicating some effectiveness in managing advanced melanoma.

The treatment was well-tolerated with no adverse events reported, and the median survival for patients was 8.9 months, suggesting that this experimental therapy may provide a new avenue for treatment without significant toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of patient survival in a Phase I trial of systemic targeted α-therapy for metastatic melanoma. Allen, BJ., Singla, AA., Rizvi, SM., et al.[2022]

Targeted alpha-particle therapy using monoclonal antibodies to deliver radioisotopes directly to tumor cells shows promise for more effective tumor cell killing while minimizing damage to surrounding healthy tissues, making it suitable for treating minimal residual disease.

Clinical trials have confirmed the safety and feasibility of this therapy, but further research is needed to explore more potent isotopes and improve delivery methods to establish its clinical effectiveness compared to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The promise of targeted {alpha}-particle therapy. Mulford, DA., Scheinberg, DA., Jurcic, JG.[2022]

Targeted alpha-particle therapy (TAT) offers a promising approach for cancer treatment due to its high potency and specificity, allowing for the effective killing of individual cancer cells through self-irradiation.

Clinical trials using various radionuclides, such as (213)Bi and (223)Ra, have demonstrated the therapeutic advantages of TAT, particularly in treating castration-resistant prostate cancer, although challenges like limited radionuclide availability remain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential and hurdles of targeted alpha therapy - clinical trials and beyond. Elgqvist, J., Frost, S., Pouget, JP., et al.[2022]

α-Particle irradiation is gaining recognition as a powerful treatment for cancer, with unique properties that enhance its effectiveness in targeted therapy.

Clinical studies have shown that α-particle emitters are safe and effective for treating conditions like leukemia and metastatic cancer, highlighting their potential as tumor-selective therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted and Nontargeted α-Particle Therapies. McDevitt, MR., Sgouros, G., Sofou, S.[2020]

Citations

1. perspectivetherapeutics.com perspectivetherapeutics.com/pr/perspective-therapeutics-progresses-dose-finding-for-212pbvmt01-in-combination-with-nivolumab-in-its-ongoing-phase-12a-study-of-mc1rpositive-metastatic-melanoma

Press Release Patients in this cohort are receiving [212Pb]VMT01 at 3.0 mCi in combination with nivolumab, a PD-1 blocking antibody developed and marketed by ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3099

Interim safety and efficacy data of [ 212 Pb]VMT01 in MC1R ... Cohort 1 participants showed prolonged stabilization of disease from start of treatment (mean: 11.1 months); one participant developed a ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8345035/

Targeted Alpha-Particle Radiotherapy and Immune ... These results indicate that both single and fractionated injection of [212Pb]VMT01 monotherapy efficiently attenuated MC1R-postive melanoma ...

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/391457

MC1R-targeted Alpha-particle Monotherapy and ... In this first-in human, phase I/IIa study, the safety and efficacy of \[212Pb\]VMT01, an alpha-particle emitting therapeutic agent targeted ...

5. curetoday.com curetoday.com/view/first-patient-dosed-in-trial-of-212pb-vmt01-for-metastatic-melanoma

First Patient Dosed in Trial of [212Pb]VMT01 for Metastatic ... The first patient has been dosed with [212Pb]VMT01 in a phase 1/2a trial evaluating the safety of the agent in patients with melanoma.

6. ascopubs.org ascopubs.org/doi/pdfdirect/10.1200/JCO.2025.43.16_suppl.3099

Interim safety and efficacy data of [212Pb]VMT01 in MC1R ... Methods: This is a first-in- human dose-finding study to determine the safety, pharmacokinetics, dosimetry and pre- liminary efficacy of [212Pb]VMT01 in ...