Melanoma Vaccine Against Neoantigen and Shared Antigens by CD40 Activation and TLR Agonists In Patients With Melanoma (Including Ocular Melanoma)

NCT04364230 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: HSR200006
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

This study evaluates whether it is safe to administer a peptide vaccine made of 6MHP and a mutated neoantigen peptide (BRAF585-614-V600E) combined with adjuvants. The adjuvants that will be used in this trial are a CD40 antibody (CDX-1140) and a toll-like receptor (TLR) 3 agonist (Poly-ICLC). The study will also investigate the effects of the vaccine and the adjuvants on the immune response. The investigators will monitor these effects by performing tests in the laboratory on participants' blood and skin tissue.

Conditions

Melanoma; Ocular Melanoma; Uveal Melanoma

Keywords

peptide; vaccine; 6MHP; adjuvant; polyICLC; CDX-1140; NeoAg-mBRAF; CD40; TLR; nevi; nevus; BRAF585-614-V600E; Ocular Melanoma; Uveal Melanoma

Outcome Measures

Primary Outcomes (2)

• Safety of CDX-1140 + melanoma peptide vaccine (6MHP and NeoAg-mBRAF) + PolyICLC

  Number of participants with dose-limiting toxicities based on CTCAE v5.0

  30 days after receiving the last dose of study drug

• Immunogenicity: Estimate immune response rate to a melanoma vaccine combined with CDX-1140

  Number of participants with durable or persistent CD4+ Th1 responses to the melanoma vaccine at either day 85 or day 176, or both

  Day 85 and/or Day 176

Secondary Outcomes (4)

• Immunogenicity: Impact of vaccine containing peptides plus CDX-1140 and polyICLC on regulatory T cells

  Day 50

• Immunogenicity: Impact of addition of CDX-1140 to melanoma vaccine on circulating regulatory T cells

  Through Day 85

• Immunogenicity: Impact of addition of CDX-1140 to melanoma vaccine on induction of CD4+ Th1 responses to vaccine antigens

  Through Day 176

• Immunogenicity: Impact of addition of CDX-1140 to melanoma vaccine on CD4+ Th1 memory response to vaccine antigens

  Day 176

Study Arms (1)

All Participants

EXPERIMENTAL

6MHP (200mcg of each peptide) and 300mcg of NeoAg-mBRAF will be co-administered locally with 0.9mg of polyICLC and CDX-1140. There will be a dose escalation of CDX-1140 (50mcg, 200mcg, 800mcg, 3.0mg). A vaccine containing all of these components will be given on days 1, 22, 43, and 64. The vaccine will be given subcutaneously/intradermally.

Drug: 6MHP; Drug: NeoAg-mBRAF; Drug: PolyICLC; Drug: CDX-1140

Interventions

6MHP DRUG

6 melanoma helper vaccine comprised of 6 class II MHC-restricted helper peptides

Also known as: 6 melanoma helper peptide vaccine

All Participants

NeoAg-mBRAF DRUG

BRAF 586-614 (V600E) peptide to which a histidine has been added to the N-terminus, resulting in BRAF 585-614 (V600E).

Also known as: BRAF 585-614 (V600E)

All Participants

PolyICLC DRUG

polyICLC, local adjuvant

All Participants

CDX-1140 DRUG

CDX-1140, local adjuvant

All Participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• a. For individuals with primary cutaneous, mucosal, or unknown melanoma, an individual must have stage IB ulcerated, II, III, or IV melanoma at original diagnosis or at restaging after recurrence, and be rendered clinically free of disease by surgery, other therapy, or spontaneous remission within 6 months prior to registration.
• b. For patients with stage II, III, or IV uveal melanoma, patients must be rendered clinically free of disease by surgery, other therapy, or spontaneous remission within 6 months prior to registration.
• An individual with small radiologic or clinical findings of an indeterminate nature may still be eligible
• An individual may have had cutaneous, uveal, mucosal primary melanoma, or an unknown primary melanoma.
• Biopsies of nevi are optional. Participants with at least 4-10 evaluable nevi at least 4 mm in diameter that are located on truncal or non-acral extremity sites and are accessible for biopsy and observation will be asked to participate in the optional nevi biopsies
• Diagnosis of melanoma must be confirmed by cytological or histological examination except that patients with clinically localized primary uveal melanoma will not require pathologic review.
• Individuals will be required to have radiological studies to rule out radiologically evident melanoma metastasis.
• Individuals 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.
• ECOG performance status of 0 or 1 (Section 13.3).
• Ability and willingness to give informed consent.

You may not qualify if:

• Individuals who have received 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, with some qualifications and exceptions
• Growth factors (e.g. Procrit®, Aranesp®, Neulasta®)
• Interleukins (e.g. Proleukin®)
• Any investigational medication
• Targeted therapies specific for mutated BRAF or for MEK
• Individuals who are currently receiving nitrosoureas or who have received this therapy within 6 weeks of registration.
• Individuals who are currently receiving a checkpoint molecule blockade therapy, or who have received this therapy within 12 weeks of registration.
• Individuals with known or suspected allergies to any component of the vaccine.
• Individuals who have received prior melanoma vaccinations with 6MHP plus the mutated BRAF peptide. However, participants who have received prior vaccinations will be eligible to enroll 12 weeks following their last vaccination if they have recurred during or after administration of the vaccine, and if their vaccines did not include all of the synthetic peptides included in this protocol.
• Individuals who have previously received CDX-1140 or another CD40 agonistic antibody.

Sponsors & Collaborators

• Craig L Slingluff, Jr: lead
• Celldex Therapeutics: collaborator

Study Sites (2)

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Melanoma; Uveal Melanoma; Nevus

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases

Study Officials

• Craig L. Slingluff, Jr., MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Surgery; Director, Human Immune Therapy Center

Study Record Dates

• First Submitted: April 21, 2020
• First Posted: April 28, 2020
• Study Start: September 28, 2020
• Primary Completion: March 14, 2024
• Study Completion: March 14, 2024
• Last Updated: July 16, 2024

Record last verified: 2024-07

Locations

US (2)