Targeted treatment for metastatic uveal melanoma using alpha particle radiotherapy

First in Human Phase I Study of 225Actinium-MTI-201 (225Ac-MTI-201) in Metastatic Uveal Melanoma

This study is testing a new treatment using a special type of radiation to see if it can help people with advanced uveal melanoma who haven't had success with other therapies.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Modulation Therapeutics, Inc. (Industry-sponsored)
• Drugs / interventions: radiation, prednisone
• Locations: 1 site (Tampa, Florida)
• Trial ID: NCT05496686 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to determine the maximum-tolerated dose of 225Ac-MTI-201 in patients with metastatic uveal melanoma who have not responded to at least one prior therapy. Participants will receive a single intravenous dose of the treatment, followed by monitoring for safety and efficacy through various assessments, including vital signs, blood tests, and tumor measurements over several years. The study employs a continual reassessment method for dose escalation, ensuring patient safety while exploring effective treatment options.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed metastatic uveal melanoma that has progressed after at least one prior line of therapy.

Not a fit: Patients with non-metastatic uveal melanoma or those who have not experienced disease progression after previous treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with metastatic uveal melanoma who have limited treatment choices.

How similar studies have performed: While this approach is novel in the context of metastatic uveal melanoma, similar targeted radiotherapy methods have shown promise in other cancer types.

Eligibility criteria

Inclusion Criteria:

* Histologically confirmed metastatic uveal melanoma.
* Progression after at least one prior line of therapy for metastatic uveal melanoma. Liver directed therapy (e.g., hepatic arterial embolization, isolated hepatic perfusion) will count as one line of therapy. Should any additional treatment(s) receive regulatory approval for metastatic uveal melanoma during the conduct of this trial, participants (if eligible for the newly approved treatment) would need to demonstrate disease progression on the additional treatment(s) before being eligible to participate in the current study. There is no limit to the number of previous treatments for metastatic disease.
* Participants must have measurable disease per RECIST 1.1.
* Adults, age 18 or over, with no upper age limit.
* ECOG (Eastern Cooperative Oncology Group) performance status of 0-1 (Karnofsky ≥ 70 percent).
* Acceptable organ and marrow function as defined below:

  * Leucocytes ≥ 3,000/μL
  * Absolute neutrophil count ≥ 1,500/μL
  * Platelets ≥ 100,000/μL
  * Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT) ≤ 2.5x institutional upper limit of normal (ULN)
  * Bilirubin ≤ 1.5x institutional upper limit of normal (ULN)
  * Creatinine clearance ≥ 60mL/min/1.73m\^2 (measured by Cockcroft-Gault equation using actual body weight in kilograms, and then adjusted for body surface area)
* Male participants who are sexually active, and female participants of childbearing potential must agree to use 2 forms of FDA approved contraceptive methods during treatment with 225Ac-MTI-201 and up to 3 months following treatment.
* Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* Prior alpha-particle therapy.
* Has known symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are stable without evidence of progression by imaging for at least four weeks after definitive intervention and using no more than the equivalent of dexamethasone 2 mg/d for the management of vasogenic edema, if necessary. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
* Participants with an active malignancy requiring anticancer treatment at the time of study entry that, in the judgment of the investigator could impact the results of treatment of metastatic uveal melanoma.
* Pregnant or nursing women. Women of childbearing potential (defined as having had a menstrual cycle within the past 12 months, and not having had a surgical procedure for sterilization) must have a negative pregnancy test (urine or serum) within 7 days of treatment with 225Ac-MTI-201.
* Participants with uncontrolled inter-current illness including, but not limited to, ongoing or active bacterial infection, active hepatitis B/C infection requiring antiviral therapy, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Immunocompromised participants may be at increased risk of toxicity. Therefore, HIV-positive participants, participants with acquired or congenital immunodeficiency conditions, those on chronic systemic corticosteroids requiring \>10 mg of prednisone or equivalent per day will be excluded from participation. (Participants with autoimmune disease who do not require corticosteroids or are maintained on ≤10 mg of prednisone or equivalent per day ARE eligible for participation; for participants with CNS metastases on steroids, exclusion criterion bullet point #2 above will apply).
* Prior external beam radiation therapy to more than 25 percent of the bone marrow.

Where this trial is running

Tampa, Florida

• H. Lee Moffitt Cancer Center and Research Institute — Tampa, Florida, United States (Recruiting)

Study contacts

• Principal investigator: Nikhil I Khushalani, MD — H. Lee Moffitt Cancer Center and Research Institute
• Study coordinator: Mark L McLaughlin, PhD

Conditions Uveal Melanoma; Metastatic; Uveal Neoplasms; Melanoma of the Uvea; Melanocortin 1 Receptor; MC1R; Peptide Receptor Radiotherapeutic; PRRT