Neoadjuvant Pembrolizumab for Unresectable Stage III and Unresectable Stage IV Melanoma
Condition: Unresectable Malignant Neoplasm; Melanoma; Metastatic Melanoma; Stage IV Melanoma; Stage III Melanoma
MeSH terms: Melanoma; Neoplasms
Intervention: Pembrolizumab
Intervention description: At the Treatment Initiation Visit (Baseline/Day 1), subjects will begin treatment with IV pembrolizumab 200 mg infusions every 3 weeks. As in previous pembrolizumab trials, eligible subjects will receive at least 24 weeks of therapy and may receive up to 2 years of pembrolizumab therapy depending on response to treatment.
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: immunotherapy; PD-1 inhibitor; programmed death 1 inhibitor; neoadjuvant; pembrolizumab; MK-3475

Summary:

      This study is being done to see if using the study drug, pembrolizumab, can shrink down
      melanoma tumors enough so that they will be small enough to cut out, so that there will be no
      cancer left in the body.

      Eligible participants include those who have not received any systemic melanoma therapies
      (i.e. participants do not have to fail ipilimumab or BRAF inhibitor) and those who have
      failed all available systemic options (if the participant meets other inclusion / exclusion
      criteria).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Be able to provide written informed consent.

          2. Be 18 years old at time of consent.

          3. Have measurable disease by RECIST 1.1.

          4. Has a diagnosis of unresectable Stage III or Stage IV melanoma with anatomic site(s)
             of metastasis that could be amenable to curative resection if the site(s) decreased in
             size by up to 50% (at the investigators' discretion).

          5. Have provided tissue sample of a tumor lesion.

          6. Have an ECOG Performance status 0 or 1.

          7. Demonstrate adequate organ function according to pre-defined criteria

          8. Females of childbearing potential should have a negative pregnancy test within 72
             hours prior to receiving the first dose.

          9. Females of childbearing potential should be willing to use 2 methods of birth control
             or be surgically sterile, or abstain from heterosexual activity during the study
             through 120 days after last dose. Subjects of childbearing potential are those who
             have not been surgically sterilized or have not been free from menses for > 1 year.

        10 . Males should agree to use an adequate method of contraception starting with the first
        dose of therapy through 120 days after last dose.

        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. 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
             treatment.

          3. 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 > 4 weeks earlier.

          4. Has had prior chemotherapy, targeted small molecule therapy, or 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.

          5. Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell and squamous cell skin cancers, or in situ cervical
             cancer.

          6. Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Subjects with previously treated brain metastases may participate provided
             they are stable (without evidence of progression by imaging 4 weeks prior to the first
             dose and any neurologic symptoms have returned to baseline), have no evidence of new
             or enlarging brain metastases, and are not using steroids for 7 days prior to trial
             treatment.

          7. Has an active autoimmune disease requiring systemic treatment within the past 3 months
             or a history of severe autoimmune disease or syndrome that requires steroids or
             immunosuppressive agents.

          8. Has interstitial lung disease or active, non-infectious pneumonitis.

          9. Has an active infection requiring systemic therapy.

         10. Has a history or current evidence of any condition, therapy, or lab abnormality that
             might confound the results, interfere with the subject's participation, or is not in
             the best interest of the subject to participate, in the opinion of the investigator.

         11. Has known psychiatric or substance abuse disorders that would interfere with the
             requirements of the trial.

         12. Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial.

         13. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 treatment.

         14. Has a history of HIV.

         15. Has active Hepatitis B or Hepatitis C

         16. Has received a live vaccine within 30 days prior to first dose.

         17. Is currently being treated with ipilimumab (defined as ipilimumab < 6 weeks before
             first dose of treatment).