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

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Brief Title

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

Official Title

Enhanced Melanoma Vaccine Against Neoantigen and Shared Antigens by CD40 Activation and TLR Agonists in Patients With Melanoma

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.
    


Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

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

Secondary Outcome

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

Condition

Melanoma

Intervention

6MHP

Study Arms / Comparison Groups

 All Participants
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

44

Start Date

September 28, 2020

Completion Date

May 2025

Primary Completion Date

September 2024

Eligibility Criteria

        Main Inclusion Criteria:

          1. 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.

          2. An individual with small radiologic or clinical findings of an indeterminate nature
             may still be eligible

          3. An individual may have had cutaneous, uveal, mucosal primary melanoma, or an unknown
             primary melanoma.

          4. 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

          5. 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.

          6. Individuals will be required to have radiological studies to rule out radiologically
             evident melanoma metastasis.

          7. 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.

          8. The most recent surgical resections or gamma-knife therapy for malignant melanoma must
             have been completed ≥ 1 week and ≤ 6 months prior to registration.

          9. ECOG performance status of 0 or 1 (Section 13.3).

         10. Ability and willingness to give informed consent.

         11. Adequate organ function as determined by laboratory parameters.

         12. Male or female, age 18 years or older at registration.

         13. Individuals must have at least one intact (undissected) axillary and/or inguinal lymph
             node basin.

         14. For females and males of reproductive potential: agreement to use adequate
             contraception during study participation and for an additional 3 months after
             receiving the last dose of study drug.

        Main Exclusion Criteria:

          1. 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

          2. Individuals who are currently receiving nitrosoureas or who have received this therapy
             within 6 weeks of registration.

          3. Individuals who are currently receiving a checkpoint molecule blockade therapy, or who
             have received this therapy within 12 weeks of registration.

          4. Individuals with known or suspected allergies to any component of the vaccine.

          5. 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.

          6. Individuals who have previously received CDX-1140 or another CD40 agonistic antibody.

          7. Pregnancy. Female individuals of childbearing potential must have a negative pregnancy
             test (urinary or serum beta-HCG) obtained within 2 weeks prior to registration.

          8. HIV positivity or evidence of active Hepatitis C virus (testing to be done within 6
             months of study entry).

          9. Female individuals must not be breastfeeding.

         10. Individuals in whom there is a medical contraindication or potential problem in
             complying with the requirements of the protocol in the opinion of the investigator.

         11. Individuals classified according to the New York Heart Association classification as
             having Class III or IV heart disease (Section 13.4).

         12. Individuals must not have had prior autoimmune disorders requiring systemic cytotoxic
             or immunosuppressive therapy, or autoimmune disorders with visceral involvement.
             Participants with an active autoimmune disorder requiring these therapies are also
             excluded. Some autoimmune disorders will not be exclusionary:

               -  The presence of laboratory evidence of autoimmune disease (e.g. positive ANA
                  titer) without symptoms

               -  Clinical evidence of vitiligo

               -  Other forms of depigmenting illness

               -  Mild arthritis requiring non-steroidal anti-inflammatory drugs (NSAID)
                  medications

               -  Resolved childhood asthma/atopy

               -  Endocrinopathies on stable hormone replacement therapy

         13. Individuals 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.

         14. Individuals with current pneumonitis. Individuals must not have had pneumonitis within
             30 days of registration. Patients who have had complete resolution of prior
             pneumonitis will be eligible.

         15. Individuals who have received a live vaccine within 30 days of registration.

         16. Body weight < 110 pounds (50 kg) at registration
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Craig Slingluff, 1-434-982-6714, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04364230

Organization ID

HSR200006


Responsible Party

Sponsor-Investigator

Study Sponsor

Craig L Slingluff, Jr

Collaborators

 Celldex Therapeutics

Study Sponsor

Craig Slingluff, Principal Investigator, University of Virginia


Verification Date

April 2022