MC1R-targeted Alpha-particle Therapy Trial in Adults With Advanced Melanoma

Phase 1

Recruiting

• Conditions: Metastatic Melanoma; Melanoma, Uveal; Mucosal Melanoma; Melanoma (Skin); Melanoma Stage IV; Melanoma Stage III

• Registration Number: NCT05655312
• Lead Sponsor: Perspective Therapeutics

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-11-15
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Inclusion Criteria:<br><br> - Ability to understand and willingness to provide informed consent, willingness to<br> comply with all study procedures for the duration of the study<br><br> - Male or female, aged = 18 years<br><br> - Diagnosed with Stage IV metastatic melanoma, or unresectable Stage III<br><br> - Previously progressed (clinical or radiological progression) on at least one prior<br> therapy for metastatic melanoma<br><br> - Uptake of [68Ga]VMT02 or [203Pb]VMT01 by PET or SPECT imaging observed in at least<br> one melanoma tumor site using quantitative imaging analysis compared to reference<br> normal tissue<br><br> - Subjects on prior intravenous therapy (e.g., chemotherapy or checkpoint inhibitors),<br> or prior oral therapy (e.g., BRAF or MEK inhibitors) who demonstrate MC1R positivity<br> during screening are eligible for enrollment, provided that they undergo a wash-out<br> period of 21 days, or 14 days, respectively, prior to Day 1 treatment with<br> [212Pb]VMT01.<br><br> - Presence of measurable disease by RECIST v1.1 criteria assessed within 30 days prior<br> to the start of Day 1<br><br> - Ability to lie flat and still for up to two hours for imaging scans; moderate<br> conscious sedation allowed if indicated<br><br> - For females of reproductive potential: use of highly effective contraception for at<br> least one month prior to screening, and agreement to use such a method during study<br> participation and for an additional four weeks after the last administration of an<br> investigational product<br><br> - For males of reproductive potential: use of condoms or other methods to ensure<br> effective contraception with partner during study participation and for an<br> additional four weeks after the last administration of an investigational product<br><br> - ECOG performance score of < 2 at Screening<br><br> - Life expectancy of at least 3 months<br><br> - Evidence of sufficient organ function as determined by all of the following:<br><br>Oxygen saturation > 90% on room air eGFR > 50 mL/min/1.73m2 by CKD-EPI equation Complete<br>blood count with differential, within 7 calendar days prior to therapy and off Growth<br>Factors White blood cells (WBC) > 2500/mm3 Hemoglobin (Hgb) > 9.0 g/dL Platelets ><br>60,000/mm3 Absolute Neutrophil Count (ANC) > 1,250/mm3<br><br>The comprehensive metabolic panel, within seven calendar days prior to Day 1,<br>demonstrating values within the site's upper limit of normal (ULN), with the following<br>exceptions:<br><br>Alanine aminotransferase (ALT) < 3x ULN Aspartate aminotransferase (AST) < 3x ULN<br>Alkaline phosphatase (ALP) < 2.5x ULN<br><br>Exclusion Criteria:<br><br> - Active secondary malignancy<br><br> - Prior treatment (for any reason) with radioactive nuclides; however, imaging tracers<br> are acceptable<br><br> - Pregnancy or breastfeeding a child<br><br> - Active infection<br><br> - Brain metastasis requiring acute therapy of any modality (i.e., surgical or external<br> beam radiotherapy) within two weeks of enrollment or clinical instability, including<br> signs or symptoms of brain edema. Subjects must demonstrate stable or decreasing<br> brain metastasis by a noninvasive imaging scan and must be off steroids or on<br> decreasing doses prior to enrollment.<br><br> - Treatment with another investigational drug product (therapeutic IND agents) within<br> the last 30 days.<br><br> - Current abuse of alcohol or illicit drugs<br><br> - Existence of any medical or social issues likely to interfere with study conductor<br> that may cause increased risk to the subject or to others, e.g., lack of ability to<br> follow radiation safety precautions

Exclusion Criteria

Not provided

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0;Number of patients with laboratory abnormalities [Time Frame: Through 42 days following last dose of [212Pb]VMT01; up to 3 years];Number of participants with dose-limiting toxicities (DLTs) through 42 days following last dose of [212Pb]VMT01-T101;Objective response rate (ORR) per RECIST 1.1 [Time Frame: up to approximately 3 years]

Secondary Outcome Measures

Name	Time	Method
Area under the concentration-time curve (AUC) [Time Frame: Through 42 days following last dose of [212Pb]VMT01; up to 3 years];Apparent terminal elimination half-life (T1/2) [Time Frame: Through 42 days following last dose of [212Pb]VMT01; up to 6 months];Duration of response (DOR) following treatment with [212Pb]VMT01;Progression free survival (PFS) treatment with [212Pb]VMT01;Overall survival (OS) following treatment with [212Pb]VMT01