Clinical Trials /

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

NCT04364230

Description:

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.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Melanoma Vaccine Against Neoantigen and Shared Antigens by CD40 Activation and TLR Agonists In Patients With Melanoma
  • Official Title: Enhanced Melanoma Vaccine Against Neoantigen and Shared Antigens by CD40 Activation and TLR Agonists in Patients With Melanoma

Clinical Trial IDs

  • ORG STUDY ID: Mel 66
  • NCT ID: NCT04364230

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
6MHP6 melanoma helper peptide vaccineArm A
NeoAg-mBRAFBRAF 585-614 (V600E)Arm A
PolyICLCArm A
CDX-1140Arm A

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Arm AExperimental6MHP (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 for both arms (50mcg, 200mcg, 800mcg, 3.0mg). A vaccine containing all of these components will be given at the primary site at days 1, 8, 16, 38, 67, and 78 and at the replicate site at day 1. A vaccine that contains all components except for CDX-1140 will be given at the replicate site at days 8 and 16. The vaccine will be given subcutaneously/intradermally.
  • 6MHP
  • NeoAg-mBRAF
  • PolyICLC
  • CDX-1140
Arm BExperimental6MHP (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 for both arms (50mcg, 200mcg, 800mcg, 3.0mg). A vaccine containing all of these components will be given at the primary site at days 1, 38, 67, and 78 and at the replicate site at days 1, 8, and 16. A vaccine that contains all components except for CDX-1140 will be given at the primary site at days 8 and 16. The vaccine will be given subcutaneously/intradermally.
  • 6MHP
  • NeoAg-mBRAF
  • PolyICLC
  • CDX-1140

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. An individual must have at least 6-10 nevi at least 4 mm in diameter that are located
             on truncal or non-acral extremity sites and are accessible for biopsy and observation.

          5. Diagnosis of melanoma must be confirmed by cytological or histological examination.

          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 two intact (undissected) axillary and/or inguinal lymph
             node basins

         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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety of CDX-1140 + melanoma peptide vaccine (6MHP and NeoAg-mBRAF) + PolyICLC
Time Frame:30 days after receiving the last dose of study drug
Safety Issue:
Description:Number of participants with dose-limiting toxicities based on CTCAE v5.0

Secondary Outcome Measures

Measure:Immunogenicity: Impact of CDX-1140 on regulatory T cells
Time Frame:Day 8 and Day 22
Safety Issue:
Description:Number of FoxP3+ CD4+ T cells per mm^2 in vaccine site biopsies
Measure:Immunogenicity: Impact of addition of CDX-1140 to melanoma vaccine on circulating regulatory T cells
Time Frame:Through Day 85
Safety Issue:
Description:Number of participants with circulating Tregs (CD4+ FoxP3+) as a proportion of circulating CD4 T cells
Measure:Immunogenicity: Impact of addition of CDX-1140 to melanoma vaccine on frequency of CD4+ Th1 responses to vaccine antigens
Time Frame:Through Day 176
Safety Issue:
Description:Number of participants with CD4+ T cell response; maximum increase after vaccination at any time point.
Measure:Immunogenicity: Impact of addition of CDX-1140 to melanoma vaccine on CD4+ Th1 memory response to vaccine antigens
Time Frame:Day 176
Safety Issue:
Description:Number of participants with CD4+ T cell response to the melanoma peptides

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Craig L Slingluff, Jr

Trial Keywords

  • peptide
  • vaccine
  • 6MHP
  • adjuvant
  • polyICLC
  • CDX-1140
  • NeoAg-mBRAF
  • CD40
  • TLR
  • nevi
  • nevus
  • BRAF585-614-V600E

Last Updated

September 28, 2020