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

Primary Purpose

Melanoma (Skin), Metastatic Melanoma, Melanoma Stage IV

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
[203Pb]VMT01
[212Pb]VMT01
[212Pb]VMT01
Sponsored by
Viewpoint Molecular Targeting
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma (Skin) focused on measuring Melanoma, Theranostic, Radiopharmaceutical, Radiotherapy, Alpha Particle, Melanocortin Receptor Sub-type 1 (MC1R), VMT01-T101, Pb-203, Pb-212, Ga-68

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Yale University
  • University of Iowa
  • Mayo Clinic Rochester
  • Saint Louis UniversityRecruiting
  • Washington University of St. LouisRecruiting
  • University of WisconsinRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Dose Escalation

Dose Expansion with RPh2D

Arm Description

Dose Escalation to determine MTD/MFD among 4 different dose levels in up to 32 patients receiving up to 3 administrations of [212Pb]VMT01 approximately 8 weeks apart. The second part of the study is a dose expansion based on the identified MTD/MFD for the selection of [212Pb]VMT01 dose(s) in up to 20 additional subjects for further clinical development. A dosimetry sub-study utilizing [203Pb]VMT01 has been incorporated into the study.

Up to 20 patients with advanced or metastatic melanoma

Outcomes

Primary Outcome Measures

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Any untoward medical occurrence in a clinical investigational participant administered [212Pb]VMT01 and Associated Adverse Events (AE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
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

Area under the concentration-time curve (AUC) [Time Frame: Through 42 days following last dose of [212Pb]VMT01; up to 3 years]
Pharmacokinetic (PK) endpoint
Apparent terminal elimination half-life (T1/2) [Time Frame: Through 42 days following last dose of [212Pb]VMT01; up to 6 months]
PK endpoint
Duration of response (DOR) following treatment with [212Pb]VMT01
Median DOR for subjects receiving at least 1 administration of[212Pb]VMT01, as assessed by RECIST v1.1 criteria.
Progression free survival (PFS) treatment with [212Pb]VMT01
For subjects receiving at least 1 administration of [212Pb]VMT01, assessed by RECIST v1.1 criteria.
Overall survival (OS) following treatment with [212Pb]VMT01
Median OS for subjects receiving at least 1 administration of [212Pb]VMT01.

Full Information

First Posted
November 15, 2022
Last Updated
September 27, 2023
Sponsor
Viewpoint Molecular Targeting
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1. Study Identification

Unique Protocol Identification Number
NCT05655312
Brief Title
MC1R-targeted Alpha-particle Therapy Trial in Adults With Advanced Melanoma
Official Title
A Phase I/IIa, First-In-Human, Multi-Center Dose Escalation and Dose Expansion Study of [203/212Pb]VMT01 Receptor-Targeted, Image-Guided Alpha-Particle Therapy in Patients With Previously Treated Unresectable or Metastatic Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2023 (Actual)
Primary Completion Date
June 30, 2025 (Anticipated)
Study Completion Date
June 30, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Viewpoint Molecular Targeting

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
In this first-in human, phase I/IIa study, the safety and efficacy of [212Pb]VMT01, an alpha-particle emitting therapeutic agent targeted to melanocortin sub-type 1 receptor (MC1R) is being evaluated in patients with unresectable and metastatic melanoma.
Detailed Description
This is a prospective, multi-center open-label dose escalation, dose expansion study of [212Pb]VMT01 in up to 52 subjects with histologically confirmed melanoma and a positive MC1R imaging scan ([203Pb]VMT01 or [68Ga]VMT02). MC1R is a receptor that is expressed on the surface of melanoma cells. As such MC1R represents a potentially useful means of targeting therapeutics to melanoma. Lead-212 ([212Pb]-) based peptide-radiopharmaceuticals are an emerging class of targeted alpha-particle cancer therapies which have the potential to improve delivery of a highly effective form of radiation. Patients may be eligible to receive up to 3 administrations of [212Pb]VMT01 approximately 8 weeks apart. The first part of the study is an dose-escalation study to determine the Maximum Tolerated radioactivity Dose (MTD) or Maximum Feasible radioactivity Dose (MFD) following a single administration of [212Pb]VMT01. The second part of the study is a dose expansion based on the identified MTD/MFD for the selection of [212Pb]VMT01 dose(s) for further clinical development. A dosimetry sub-study utilizing the SPECT imaging surrogate, [203Pb]VMT01, has been incorporated into the study in order to assess normal organ biodistribution, tumor uptake of the investigational products, to estimate radiation dosimetry, and to correlate uptake of the investigation products with observed toxicities and efficacy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma (Skin), Metastatic Melanoma, Melanoma Stage IV, Melanoma, Uveal, Mucosal Melanoma, Melanoma Stage III
Keywords
Melanoma, Theranostic, Radiopharmaceutical, Radiotherapy, Alpha Particle, Melanocortin Receptor Sub-type 1 (MC1R), VMT01-T101, Pb-203, Pb-212, Ga-68

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Phase I/IIa First-in-Human Study of [212Pb]VMT01 Targeted Alpha-Particle Therapy for MC1R Positive Advanced Malignant Melanoma Dose
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
52 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dose Escalation
Arm Type
Experimental
Arm Description
Dose Escalation to determine MTD/MFD among 4 different dose levels in up to 32 patients receiving up to 3 administrations of [212Pb]VMT01 approximately 8 weeks apart. The second part of the study is a dose expansion based on the identified MTD/MFD for the selection of [212Pb]VMT01 dose(s) in up to 20 additional subjects for further clinical development. A dosimetry sub-study utilizing [203Pb]VMT01 has been incorporated into the study.
Arm Title
Dose Expansion with RPh2D
Arm Type
Experimental
Arm Description
Up to 20 patients with advanced or metastatic melanoma
Intervention Type
Drug
Intervention Name(s)
[203Pb]VMT01
Intervention Description
[203Pb]VMT01 IV administered as Image agent for SPECT/CT
Intervention Type
Drug
Intervention Name(s)
[212Pb]VMT01
Intervention Description
Patients with positive uptake of [203Pb]VMT01 will receive a fixed dose of [212Pb]VMT01 IV administered every 8 weeks for a maximum of three doses. Doses range between 111 MBq to 555 MBq (3 mCi to 15 mCi)
Intervention Type
Drug
Intervention Name(s)
[212Pb]VMT01
Intervention Description
Patients with positive update of [203Pb]VMT01 will receive a fixed dose of [212Pb]VMT01 IV administered every 8 weeks at the RPh2D and schedule determined in Phase I dose escalation
Primary Outcome Measure Information:
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
Any untoward medical occurrence in a clinical investigational participant administered [212Pb]VMT01 and Associated Adverse Events (AE) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Time Frame
42 days; up to 3 years
Title
Number of patients with laboratory abnormalities [Time Frame: Through 42 days following last dose of [212Pb]VMT01; up to 3 years]
Time Frame
up to 3 years
Title
Number of participants with dose-limiting toxicities (DLTs) through 42 days following last dose of [212Pb]VMT01-T101
Time Frame
42 days; up to 3 years
Title
Objective response rate (ORR) per RECIST 1.1 [Time Frame: up to approximately 3 years]
Time Frame
up to 3 years
Secondary Outcome Measure Information:
Title
Area under the concentration-time curve (AUC) [Time Frame: Through 42 days following last dose of [212Pb]VMT01; up to 3 years]
Description
Pharmacokinetic (PK) endpoint
Time Frame
up to 3 years
Title
Apparent terminal elimination half-life (T1/2) [Time Frame: Through 42 days following last dose of [212Pb]VMT01; up to 6 months]
Description
PK endpoint
Time Frame
up to 6 months
Title
Duration of response (DOR) following treatment with [212Pb]VMT01
Description
Median DOR for subjects receiving at least 1 administration of[212Pb]VMT01, as assessed by RECIST v1.1 criteria.
Time Frame
up to approximately 3 years
Title
Progression free survival (PFS) treatment with [212Pb]VMT01
Description
For subjects receiving at least 1 administration of [212Pb]VMT01, assessed by RECIST v1.1 criteria.
Time Frame
up to approximately 3 years
Title
Overall survival (OS) following treatment with [212Pb]VMT01
Description
Median OS for subjects receiving at least 1 administration of [212Pb]VMT01.
Time Frame
up to approximately 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Ability to understand and willingness to provide informed consent, willingness to comply with all study procedures for the duration of the study Male or female, aged ≥ 18 years Diagnosed with Stage IV metastatic melanoma, or unresectable Stage III Previously progressed (clinical or radiological progression) on at least one prior therapy for metastatic melanoma Uptake of [68Ga]VMT02 or [203Pb]VMT01 by PET or SPECT imaging observed in at least one melanoma tumor site using quantitative imaging analysis compared to reference normal tissue Subjects on prior intravenous therapy (e.g., chemotherapy or checkpoint inhibitors), or prior oral therapy (e.g., BRAF or MEK inhibitors) who demonstrate MC1R positivity during screening are eligible for enrollment, provided that they undergo a wash-out period of 21 days, or 14 days, respectively, prior to Day 1 treatment with [212Pb]VMT01. Presence of measurable disease by RECIST v1.1 criteria assessed within 30 days prior to the start of Day 1 Ability to lie flat and still for up to two hours for imaging scans; moderate conscious sedation allowed if indicated For females of reproductive potential: use of highly effective contraception for at least one month prior to screening, and agreement to use such a method during study participation and for an additional four weeks after the last administration of an investigational product For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner during study participation and for an additional four weeks after the last administration of an investigational product ECOG performance score of < 2 at Screening Life expectancy of at least 3 months Evidence of sufficient organ function as determined by all of the following: Oxygen saturation > 90% on room air eGFR > 50 mL/min/1.73m2 by CKD-EPI equation Complete blood count with differential, within 7 calendar days prior to therapy and off Growth Factors White blood cells (WBC) > 2500/mm3 Hemoglobin (Hgb) > 9.0 g/dL Platelets > 60,000/mm3 Absolute Neutrophil Count (ANC) > 1,250/mm3 The comprehensive metabolic panel, within seven calendar days prior to Day 1, demonstrating values within the site's upper limit of normal (ULN), with the following exceptions: Alanine aminotransferase (ALT) < 3x ULN Aspartate aminotransferase (AST) < 3x ULN Alkaline phosphatase (ALP) < 2.5x ULN Exclusion Criteria: Active secondary malignancy Prior treatment (for any reason) with radioactive nuclides; however, imaging tracers are acceptable Pregnancy or breastfeeding a child Active infection Brain metastasis requiring acute therapy of any modality (i.e., surgical or external beam radiotherapy) within two weeks of enrollment or clinical instability, including signs or symptoms of brain edema. Subjects must demonstrate stable or decreasing brain metastasis by a noninvasive imaging scan and must be off steroids or on decreasing doses prior to enrollment. Treatment with another investigational drug product (therapeutic IND agents) within the last 30 days. Current abuse of alcohol or illicit drugs 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Markus Puhlmann, MD
Phone
319-665-2151
Email
mpuhlmann@perspectivetherapeutics.com
Facility Information:
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
Phone
203-785-5102
First Name & Middle Initial & Last Name & Degree
Mariam Aboian, MD/PhD
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yusuf Menda, MD
First Name & Middle Initial & Last Name & Degree
Yousef Zakharia, MD
Facility Name
Mayo Clinic Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthew S Block, MD, PhD
First Name & Middle Initial & Last Name & Degree
Geoffrey B Johnson, MD, PhD
Facility Name
Saint Louis University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martha Edwards, BSN, RN
Phone
314-977-4498
First Name & Middle Initial & Last Name & Degree
Medhat Osman, MD
Facility Name
Washington University of St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
314-362-7100
First Name & Middle Initial & Last Name & Degree
Richard Wahl, MD
Facility Name
University of Wisconsin
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Diana Trask
Email
trask@humonc.wisc.edu
First Name & Middle Initial & Last Name & Degree
Zachary S Morris, MD, PhD
First Name & Middle Initial & Last Name & Degree
Vincent Ma, MD

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
Protocol, CSR

Learn more about this trial

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

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