Clinical Trials /

Safety Study of a Helper Peptide Vaccine Plus Pembrolizumab

NCT02515227

Description:

This study evaluates whether it is safe to administer a peptide vaccine in combination with pembrolizumab. This study will also evaluate the effects of the combination of the peptide vaccine and pembrolizumab on the immune system. The investigators will monitor these effects by performing tests in the laboratory on participants' blood, a lymph node, and tumor samples.

Related Conditions:
  • Melanoma
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety Study of a Helper Peptide Vaccine Plus Pembrolizumab
  • Official Title: A Trial to Evaluate the Safety, Immunogenicity, and Clinical Activity of a Helper Peptide Vaccine Plus PD-1 Blockade

Clinical Trial IDs

  • ORG STUDY ID: 18174
  • SECONDARY ID: R01CA178846
  • NCT ID: NCT02515227

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
6MHP6 melanoma helper peptide vaccine6MHP + Pembrolizumab
PembrolizumabKEYTRUDA, MK-34756MHP + Pembrolizumab

Purpose

This study evaluates whether it is safe to administer a peptide vaccine in combination with pembrolizumab. This study will also evaluate the effects of the combination of the peptide vaccine and pembrolizumab on the immune system. The investigators will monitor these effects by performing tests in the laboratory on participants' blood, a lymph node, and tumor samples.

Trial Arms

NameTypeDescriptionInterventions
6MHP + PembrolizumabExperimental6 MHP (200 mcg each peptide) will be administered intradermally and subcutaneously on days 1, 8, 15, 43, 64, and 85. Pembrolizumab (200 mg) will be administered intravenously every 3 weeks for up to 2 years, beginning on day 1.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Ability to provide written informed consent/assent for the trial.

          2. ≥18 years of age

          3. A subject may be naïve for immunotherapy agents or have received interferon-alpha,
             ipilimumab or other CTLA-4 antibody, PD-1 antibody (or anti-PD-L1 antibody),
             interleukin-2, or prior cancer vaccines other than the 6MHP vaccine. Patients who
             have received a PD-1/PD-L1 antibody may be enrolled in either of the following
             settings:

               1. A patient who has experienced progression of melanoma during that therapy or
                  after having completed that therapy,

               2. A patient who fails to experience an objective clinical response (partial
                  response or complete response by RECIST 1.1 criteria) after either 12 weeks of
                  continuous anti-PD1 antibody or anti-CTLA4/anti-PD1 combination therapy, and is
                  a candidate to receive pembrolizumab therapy

          4. Measurable disease based on RECIST 1.1.

             Subjects will be required to have radiological studies to define radiologically
             evident disease. Required studies include:

               -  Chest CT scan,

               -  Abdominal and pelvic CT scan, and

               -  Head CT scan or MRI PET/CT fusion scan may replace scans of the chest, abdomen,
                  and pelvis.

          5. Subjects who have metastatic melanoma available for biopsy pretreatment and on day 22
             must consent to having those biopsies. These metastases may be in nodes, skin, soft
             tissue, liver, or other sites that can be accessed safely by needle biopsy,
             incisional or excisional biopsy, with or without image guidance. The lesions to be
             biopsied must be specified at study enrollment and not included as target lesions for
             RECIST calculations. In instances where disease that is accessible to biopsy is
             limited, archival tissue specimens collected after a subject's last systemic therapy
             may be used for baseline measures.

             Subjects must have measurable disease in addition to the lesion(s) to be biopsied.

          6. Subjects 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.

               -  There has been no evident growth of any brain metastasis since the most recent
                  treatment

               -  No brain metastasis is > 2 cm in diameter at the time of registration.

               -  Neurologic symptoms have returned to baseline,

               -  There is no evidence of new or enlarging brain metastases,

               -  Subjects are not using steroids for at least 7 days prior to registration.

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

          8. ECOG performance status of 0 or 1

          9. Adequate organ function.

         10. Two intact (undissected) axillary and/or inguinal lymph node basins.

        Exclusion Criteria

          1. Is currently participating in or has participated in a study of an investigational
             agent or using an investigational device within 4 weeks of the first dose of
             treatment.

          2. Is currently receiving Interferon (e.g. Intron-A®), growth factors (e.g. Procrit®,
             Aranesp®, Neulasta®), or interleukins (e.g. Proleukin®), or has received these agents
             within 4 weeks of the first dose of treatment.

          3. Is currently receiving nitrosureas or has received this therapy within the preceding
             6 weeks of first dose of treatment.

          4. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of
             trial treatment with the following exceptions (which are permitted):

               -  replacement steroid doses in patients with adrenal or pituitary insufficiency

               -  Intra-articular steroid injections

               -  Inhaled steroids (e.g.: Advair®, Flovent®, Azmacort®) at low doses (less than
                  500 mcg fluticasone per day, or equivalent)

               -  Topical and nasal corticosteroids

               -  Non-steroidal anti-inflammatory drugs

          5. Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has
             not recovered (i.e. ≤ Grade 1 or at baseline) from adverse events due to agents
             administered more than 4 weeks earlier.

          6. Has had prior chemotherapy, targeted small molecule therapy, or external beam
             radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e.,
             ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.

               -  Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and
                  may qualify for the study.

               -  Note: If subject received major surgery, they must have recovered adequately
                  from the toxicity and/or complications from the intervention prior to starting
                  therapy.

          7. Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include carcinoma in situ of the breast (DCIS or LCIS), basal cell
             carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical
             cancer that has undergone potentially curative therapy.

          8. Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis.

          9. Has an active autoimmune disease requiring systemic treatment within the past 3
             months or a documented history of clinically severe autoimmune disease, or a syndrome
             that requires systemic steroids or immunosuppressive agents. Exceptions to this
             criterion include:

               -  Subjects with vitiligo or other depigmenting illness.

               -  Resolved childhood asthma/atopy

               -  Intermittent use of bronchodilators or local steroid injections

               -  Hypothyroidism stable on hormone replacement or Sjogren's syndrome

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

               -  Mild arthritis requiring NSAID medications

         10. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.

         11. Has an active infection requiring systemic therapy.

         12. Has a history or current evidence of any condition, therapy, or laboratory
             abnormality that might confound the results of the trial, interfere with the
             subject's participation for the full duration of the trial, or is not in the best
             interest of the subject to participate, in the opinion of the treating investigator.

         13. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

         14. Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment.

         15. Is HIV positive or has evidence of active Hepatitis C virus (testing to be done
             within 6 months of study entry) or active Hepatitis B virus.

         16. Has received a live vaccine or allergy desensitization injections within 30 days
             prior to the first dose of trial treatment.

         17. Has known or suspected allergies to any component of the vaccine.

         18. Has been vaccinated previously with any of the synthetic peptides included in this
             protocol.

         19. Is classified according to the New York Heart Association classification as having
             Class III or IV heart disease (Appendix 12.5).

         20. Has uncontrolled diabetes, defined as having a HGBA1C > 7.5%.

         21. Has a body weight < 110 pounds (without clothes) at enrollment, due to the amount and
             frequency with which blood will be drawn.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse event profile for the combination of pembrolizumab and 6MHP.
Time Frame:30 days after the last administration of study drug.
Safety Issue:
Description:Measurements of CD4+ T cell responses to the peptide vaccine.

Secondary Outcome Measures

Measure:Number of T cells in the tumor microenvironment
Time Frame:up to week 104
Safety Issue:
Description:Evaluation of tumor infiltration by CD4+ and CD8+ T cells.
Measure:Level of Th1-dominant immune signatures in the tumor microenvironment
Time Frame:up to week 104
Safety Issue:
Description:Evaluation of cytokine profile for CD4+ T cells.
Measure:Number of CD8+ T cell responses to defined melanoma antigens
Time Frame:up to week 104
Safety Issue:
Description:Evaluation of epitope-spreading through the measurement of the induction of CD8+ T cell responses to defined melanoma antigens.
Measure:Amount of IgG antibody specific for 6MHP as measured in the blood and the sentinel immunized node
Time Frame:up to week 104
Safety Issue:
Description:Evaluation of antibody responses to 6MHP

Details

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

Trial Keywords

  • peptide
  • vaccine
  • Montanide ISA-51
  • pembrolizumab
  • PD-1
  • KEYTRUDA

Last Updated

November 10, 2016