Targeted Alpha Particle Radiotherapy for Metastatic Uveal Melanoma

Study at a glance

From the registry record, last updated by the sponsor on 3 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

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

ClinicalTrials.gov ID

NCT05496686

Acronym / sponsor ID

MCC 19868

Conditions

Uveal Melanoma, Metastatic

Keywords

Uveal Neoplasms, Melanoma of the Uvea, Melanocortin 1 Receptor, MC1R, Peptide Receptor Radiotherapeutic, PRRT, Actinium-225-PRRT

Phase

Phase 1

Study type

Interventional

Recruitment status

Active, not recruiting

Enrolment

16 participants (estimated)

Lead sponsor

Modulation Therapeutics, Inc.Industry (pharma, biotech, devices)

Collaborators

H. Lee Moffitt Cancer Center and Research Institute

Study start

21 Jul 2022 (actual)

Primary completion

31 Mar 2027 (estimated)

Study completion

25 Feb 2029 (estimated)

First posted

11 Aug 2022 (actual)

Results

Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Non-randomised

Intervention model

Sequential

Masking

None (open label)

Number of arms

12

Model description

The continual reassessment method (CRM) will be used for this study. The dose escalation plan is for a doubling of the dose for doses 2 through 6, a 1.67-fold increase for doses 7 and 8, and a 1.33-fold increase for doses 9-12. This plan corresponds roughly to the modified Fibonacci dose escalation plan given by Penel and Kramar.

Who may qualify

Ages

18 years and older

Sex

All

Healthy volunteers

Not accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Maximum Tolerated Dose (MTD) of 225Ac-MTI-201

   Time frame: Within 4 weeks after study drug administration

   MTD will be determined by testing increasing doses up to 1327 microCi of 225Ac-MTI-201, administered as a single dose via IV on dose escalation cohorts 1 to 12 with 1 to 6 participants each. The MTD is reached when 6 patients receive the same highest tolerated dose of 225Ac-MTI-201. If dose-limiting toxicity (DLT) consistently occurs at the next higher dose of 225Ac-MTI-201, then 5 additional doses at the previous dose of 225Ac-MTI-201 will mark the end of clinical trial.

2. Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

   Time frame: Within 4 weeks after study drug administration

   The following will constitute a DLT if the occurrence was within 4 weeks post-dose: 1. Any death not due to the underlying disease or extraneous cause 2. Absolute neutrophil count < 0.5 X 10^9/L or the development of febrile neutropenia. 3. Grade 3 thrombocytopenia with significant bleeding, or any Grade 4 thrombocytopenia. 4. Laboratory abnormalities that satisfy Hy's law i.e., ALT or AST elevation > 3X ULN, total bilirubin elevation > 2X ULN, absence of initial findings of cholestasis, and no other reason can be found to explain the combination of increased ALT/AST and total bilirubin 5. Any grade 3 or higher non-hematological toxicity possibly, probably, or definitely attributed to the study drug with the following exceptions: 1) Grade 3 nausea, vomiting or diarrhea (less than 72 hours with care). 2) Grade 3 fatigue (less than 1 week). 3) Grade > 3 electrolyte abnormalities (less than 48 hours), not clinically complicated, and resolves with or without medical interventions

3. The Number of Participants Who Experienced Serious or Non-Serious Adverse Events

   Time frame: From time of signing the informed consent document until death, or lost to follow-up (approximately 3 years)

   Vital signs, physical examination, 12-lead EKG, and blood including toxicity on Days 8, 15, 22, and 29: Week 9, Follow-Up (Starting in Week 17) Adverse Event (AE), any new untoward medical occurrence or worsening of a preexisting medical condition in Participant administered study drug and that may or may not have a causal relationship with drug treatment. All AEs will be graded using the NCI CTCAE v5.0 criteria. Serious Adverse Event (SAE); an untoward medical occurrence at any dose that: Results in death; Is life-threatening; Requires inpatient hospitalization or causes prolongation of existing hospitalization; Results in persistent or significant disability/incapacity; Is a congenital anomaly/birth defect; Is an important medical event that may not be immediately life- threatening or result in death or hospitalization but, may jeopardize the participant or may require intervention to prevent one of the other serious outcomes; or, potential drug induced liver injury (DILI).

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2026.
• Background: PubMed 31779154Tafreshi NK, Doligalski ML, Tichacek CJ, Pandya DN, Budzevich MM, El-Haddad G, Khushalani NI, Moros EG, McLaughlin ML, Wadas TJ, Morse DL. Development of Targeted Alpha Particle Therapy for Solid Tumors. Molecules. 2019 Nov 26;24(23):4314. doi: 10.3390/molecules24234314.
• Background: PubMed 30733316Tafreshi NK, Tichacek CJ, Pandya DN, Doligalski ML, Budzevich MM, Kil H, Bhatt NB, Kock ND, Messina JL, Ruiz EE, Delva NC, Weaver A, Gibbons WR, Boulware DC, Khushalani NI, El-Haddad G, Triozzi PL, Moros EG, McLaughlin ML, Wadas TJ, Morse DL. Melanocortin 1 Receptor-Targeted alpha-Particle Therapy for Metastatic Uveal Melanoma. J Nucl Med. 2019 Aug;60(8):1124-1133. doi: 10.2967/jnumed.118.217240. Epub 2019 Feb 7.
• Background: PubMed 33860213Tafreshi NK, Kil H, Pandya DN, Tichacek CJ, Doligalski ML, Budzevich MM, Delva NC, Langsen ML, Vallas JA, Boulware DC, Engelman RW, Gage KL, Moros EG, Wadas TJ, McLaughlin ML, Morse DL. Lipophilicity Determines Routes of Uptake and Clearance, and Toxicity of an Alpha-Particle-Emitting Peptide Receptor Radiotherapy. ACS Pharmacol Transl Sci. 2021 Mar 12;4(2):953-965. doi: 10.1021/acsptsci.1c00035. eCollection 2021 Apr 9.
• Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

1 site in 1 country: see every site and its status.