Vaccination With 6MHP, With or Without Systemic CDX-1127, in Patients With Stage II-IV Melanoma (Mel-65)

Evaluation of Safety and Durable Immunogenicity of Melanoma Vaccination, With or Without Systemic CDX-1127, in Patients With Stage II-IV Melanoma

This study evaluates whether it is safe to administer a peptide vaccine (6MHP) with adjuvants and the CDX-1127 monoclonal antibody, and whether the adjuvants and the CDX-1127 monoclonal antibody boost immune responses to the vaccine. In this study, the adjuvants are Montanide ISA-51 and polyICLC. The investigators will monitor these effects by performing tests in the laboratory on participants' blood and tissue from a vaccine site.

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Biological: 6MHP; Drug: Montanide ISA-51; Drug: polyICLC; Drug: CDX-1127

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Samantha Schaeffer; Phone Number: 4349826714; Email: SMS6WN@uvahealth.org

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
    • Richmond, Virginia, United States, 23284
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Main Inclusion Criteria:

1. Patients with stage IIB, IIC, III, or IV melanoma at original diagnosis or at restaging after recurrence, rendered clinically free of disease by surgery, other therapy, or spontaneous remission within 6 months prior to registration.
2. Patients with small radiologic or clinical findings of an indeterminate nature may be eligible.
3. Patients with high-risk stage IIA melanoma (by DecisionDx Melanoma test, Castle Biosciences, Inc., Friendswood, TX) may be eligible.
4. Participants may have had cutaneous, uveal, mucosal primary melanoma, or an unknown primary melanoma. Diagnosis of melanoma must be confirmed by cytological or histological examination. Staging of cutaneous melanoma will be based on version 8 AJCC staging system.

5. Participants who have had brain metastases will be eligible if all of the following are true:

   • Each brain metastasis must have been completely removed by surgery or each unresected brain metastasis must have been treated with stereotactic radiosurgery.
   • No brain metastasis is > 2 cm in diameter at the time of registration.
   • Any neurologic symptoms attributable to brain metastases have returned to baseline.There is no evidence of new or enlarging brain metastases.
   • The most recent surgical resections or gamma-knife therapy for malignant melanoma must have been completed ≥ 1 week and ≤ 6 months prior to registration.
6. ECOG performance status of 0 or 1.
7. Ability and willingness to give informed consent.
8. Adequate organ function
9. Age 18 years or older at registration.

Main Exclusion Criteria:

1. The following medications or treatments at any time within 4 weeks of registration:

   • Chemotherapy
   • Interferon (e.g. Intron-A®)
   • Radiation therapy (Stereotactic radiotherapy, such as gamma knife, can be used ≥ 1 week and ≤ 6 months prior to registration)
   • Allergy desensitization injections
   • High doses of systemic corticosteroids
   • Growth factors (e.g. Procrit®, Aranesp®, Neulasta®)
   • Interleukins (e.g. Proleukin®)
   • Any investigational medication
   • Targeted therapies specific for mutated BRAF or for MEK
2. Nitrosoureas within 6 weeks of registration.
3. Checkpoint molecule blockade therapy within 12 weeks of registration.
4. Known or suspected allergies to any component of the vaccine.
5. Previous vaccination with 6MHP.
6. Prior treatment with CDX-1127 or other CD27 agonistic antibody.
7. Pregnancy.
8. HIV positivity or evidence of active Hepatitis C virus.
9. Female participants must not be breastfeeding.
10. A medical contraindication or potential problem in complying with the requirements of the protocol in the opinion of the investigator.
11. New York Heart Association classification as having Class III or IV heart disease.
12. Uncontrolled diabetes, defined as having an HgbA1c > 8.5%.
13. Prior autoimmune disorders requiring cytotoxic or immunosuppressive therapy, or autoimmune disorders with visceral involvement. Participants with an active autoimmune disorder requiring these therapies are also excluded.
14. Participants with known addiction to alcohol or drugs who are actively taking those agents, or participants with recent (within 1 year) or ongoing illicit IV drug use.
15. Participants who have received a live vaccine within 30 days of registration.
16. Body weight < 110 pounds at registration, due to the amount and frequency with which blood will be drawn.
17. Participants with prior autoimmune pneumonitis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: 6MHP/Montanide ISA-51 + polyICLC + CDX-1127; 200 mcg of 6MHP plus 0.9 mg of polyICLC emulsified in Montanide ISA-51 adjuvant will be administered subcutaneously on days 1, 8, 15, and 36. 200 mcg of 6MHP in Montanide ISA-51 adjuvant (without polyICLC) will be administered subcutaneously/intradermally on day 176. CDX-1127 (3mg/kg) will be administered intravenously on days 1, 36, and 78.	Biological: 6MHP; 6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides; Other Names: 6 melanoma helper peptide vaccine; Drug: Montanide ISA-51; Montanide ISA-51 (Incomplete Freund's Adjuvant), local adjuvant; Drug: polyICLC; polyICLC, local adjuvant; Drug: CDX-1127; CDX-1127, anti-CD27 monoclonal antibody; Other Names: Varlilumab
Experimental: Arm B: 6MHP/Montanide ISA-51 + polyICLC; 200 mcg of 6MHP plus 0.9 mg of polyICLC emulsified in Montanide ISA-51 adjuvant will be administered subcutaneously on days 1, 8, 15, and 36. 200 mcg of 6MHP in Montanide ISA-51 adjuvant (without polyICLC) will be administered subcutaneously/intradermally on day 176.	Biological: 6MHP; 6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides; Other Names: 6 melanoma helper peptide vaccine; Drug: Montanide ISA-51; Montanide ISA-51 (Incomplete Freund's Adjuvant), local adjuvant; Drug: polyICLC; polyICLC, local adjuvant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of CDX-1127 administered with a melanoma vaccine	Number of participants with dose-limiting toxicities based on CTCAE v5.0	30 days after receiving the last dose of study drug
Immunogenicity-Percent of patients with persistent CD4+ T cell responses to the 6MHP vaccine	Number of participants with CD4+ T cell responses to 6 MHP persisting to day 127 or later.	Day 127 or Day 176 or both

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunologic effect of CDX-1127 - Impact on regulatory T cells	Number of regulatory T cells per mm2 in the vaccine site microenvironment	Day 22 and Day 85 (Note: Day 85 biopsy not required for participants whose Day 85 visit would be due after IRB approval of Protocol v12-03-2020)
Immunologic effect of CDX-1127 - Percent of circulating regulatory T cells	Percent of circulating regulatory T cells among CD4+ T cells	through day 176
Immunogenicity - Frequency of circulating CD4+ Th1 responses	Number of participants with circulating CD4+ Th1 responses to vaccine antigens	through day 176
Immunogenicity-Frequency of durable CD4+ Th1 memory responses	Number of participants with durable CD4+ Th1 memory response to vaccine antigens, measured as response at two or more consecutive time points	Day 8 to Day 85
Immunogenicity-Frequency of CD4+ Th1 memory responses	Number of participants with CD4+ Th1 memory response to vaccine antigens a week after the Day 176 booster vaccine.	Day 183

Collaborators and Investigators

• Sponsor: Craig L Slingluff, Jr
• Collaborators: Celldex Therapeutics
• Investigators: Principal Investigator: Craig L Slingluff, Jr., MD, University of Virginia

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2018
• Primary Completion (Actual): January 19, 2024
• Study Completion (Actual): January 19, 2024

Study Registration Dates

• First Submitted: June 28, 2018
• First Submitted That Met QC Criteria: July 31, 2018
• First Posted (Actual): August 6, 2018

Study Record Updates

• Last Update Posted (Actual): February 6, 2024
• Last Update Submitted That Met QC Criteria: February 2, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: vaccine; adjuvant; CDX-1127; peptide; polyICLC; Montanide ISA-51; 6MHP; varlilumab
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Interferon Inducers; Poly ICLC; Monatide (IMS 3015)
• Other Study ID Numbers: 20085

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD that underlie results in a publication will be shared starting 1 year after publication.
• IPD Sharing Time Frame: Starting 1 year after publication
• IPD Sharing Access Criteria: The PI will review access requests. We may share files or share documents through a shared server.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No