CMP-001 in Combo With Nivolumab in Stage IIIB/C/D Melanoma Patients With Clinically Apparent Lymph Node Disease
Condition: Melanoma; Lymph Node Cancer
MeSH terms: Melanoma
Intervention: CMP-001; Nivolumab
Intervention description: A molecule comprised of a 30 nucleotide strand, flanked by 10 guanines on either end. The nucleotide strand is surrounded by a Qβ viral-like protein. The intended mechanism of action of CMP-001 in oncology is the activation of TLR9 in pDC within the tumor or the tumor-draining lymph nodes (tumor-associated pDC).; A fully human Ig G4 antibody that blocks PD-1. Nivolumab was initially approved by the FDA for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Nivolumab has also been FDA approved to treat patients with advanced (metastatic) squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy, as well as advanced renal cell carcinoma.
Intervention MeSH terms: Nivolumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Stage IIIB/C/D

Summary:

      The purpose this research study is to determine if the combination of nivolumab and CMP-001
      improves the likelihood of eradicating (destroying) disease in the lymph node (pathologic
      response rate).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Be willing and able to provide written informed consent for the study.

          2. Be ≥ 18 years of age on day of signing informed consent.

          3. Diagnosis of histologically or cytologically confirmed diagnosis of cutaneous melanoma
             belonging to one of the following AJCC TNM stages:

               1. Tx or T1-4 and

               2. N1b, or N1c, or N2b, or N2c, or N3b, or N3c and

               3. M0

             Patients are eligible for this trial either at presentation for primary melanoma with
             concurrent regional nodal and/or in-transit metastasis; or at the time of clinical
             detected nodal and/or in-transit recurrence; and may belong to any of the following
             groups:

               -  Primary cutaneous melanoma with clinically apparent regional lymph node
                  metastases.

               -  Clinically detected recurrent melanoma at the proximal regional lymph node(s)
                  basin.

               -  Clinically detected primary cutaneous melanoma involving multiple regional nodal
                  groups.

               -  Clinical detected nodal melanoma (if single site) arising from an unknown
                  primary.

               -  In-transit and/or satellite metastases with or without regional lymph node
                  involved permitted if considered potentially surgically resectable at baseline.

               -  NOTE: Determination of potential resectability must be made at baseline to be
                  eligible for this neoadjuvant study.

               -  NOTE: Patients with mucosal and/or uveal melanoma are not permitted to enroll.
                  Patients with melanomas of unknown primary may be enrolled at the discretion of
                  the treating investigator in discussion with Principal Investigator.

          4. Presence of injectable and measureable disease based on RECIST 1.1.

          5. Willing to undergo tumor biopsy (core, punch, incisional or excisional). Patients must
             undergo biopsy (core, punch) or open biopsy (incisional, excisional) within 4 weeks of
             registration on the study.

          6. Performance status of 0 or 1 on the ECOG Performance Scale.

          7. Demonstrate adequate organ function as defined below performed on screening labs
             obtained within 4 weeks of registration.

               -  Absolute neutrophil count (ANC) ≥1,500 /mcL

               -  Hemoglobin ≥9 g/dL or ≥5.6 mmol/L

               -  Platelets ≥100,000 / mcL

               -  Serum creatinine or Measured or calculated creatinine clearance (GFR can also be
                  used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60
                  mL/min for subject with creatinine levels > 1.5 X institutional ULN.

               -  Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with
                  total bilirubin levels > 1.5 ULN.

               -  AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN.

               -  International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless
                  subject is receiving anticoagulant therapy as long as PT or PTT is within
                  therapeutic range of intended use of anticoagulants.

               -  Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is
                  receiving anticoagulant therapy as long as PT or PTT is within therapeutic range
                  of intended use of anticoagulants.

          8. Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 7 days prior to receiving the first dose of study medication. If the
             urine test is positive or cannot be confirmed as negative, a serum pregnancy test will
             be required.

          9. Female subjects of childbearing potential should be willing to use 2 methods of birth
             control or be surgically sterile, or abstain from heterosexual activity for the course
             of the study through 26 weeks after the last dose of study medication. Subjects of
             childbearing potential are those who have not been surgically sterilized or have not
             been free from menses for > 1 year.

         10. Male subjects should agree to use an adequate method of contraception starting with
             the first dose of study therapy through 26 weeks after the last dose of study therapy.
             Note: Abstinence is acceptable if this is the usual lifestyle and preferred
             contraception for the subject.

        Exclusion Criteria:

          1. History of uveal or mucosal melanoma.

          2. 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.

          3. 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.

          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.

               -  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.

               -  Note: Subjects with autoimmune disorders of Grade 4 while on prior immunotherapy
                  will be excluded. Subjects who developed autoimmune disorders of Grade ≤ 3 may
                  enroll if the disorder has resolved to Grade ≤1 and the subject has been off
                  systemic steroids at doses >10 mg/d for at least 2 weeks.

          5. Active (i.e., symptomatic or growing) central nervous system (CNS) metastases.

          6. Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
             skin, or in situ cervical cancer that has undergone potentially curative therapy.

          7. Has a systemic disease that requires systemic pharmacologic doses of corticosteroids
             greater than 10mg daily prednisone (or equivalent). Subjects who are currently
             receiving steroids at a dose of ≤10mg daily do not need to discontinue steroids prior
             to enrollment Subjects that require topical, ophthalmologic and inhalational steroids
             would not be excluded from the study. Subjects with hypothyroidism stable on hormone
             replacement or Sjogren's syndrome will not be excluded from the study. Subjects who
             require active immunosuppression (greater than steroid dose discussed above) for any
             reason are excluded.

          8. Has evidence of 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 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.

         11. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation 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, starting with the pre-screening or screening visit
             through 26 weeks after the last dose of trial treatment.

         13. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137.
             Prior treatment with ipilimumab or interferon alfa is allowed. Patients with history
             of allergic or hypersensitivity reaction to interferon alfa or ipilimumab are also
             excluded.

         14. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

         15. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected. Patients with treated Hepatitis B/C with no evidence of
             active infection may be enrolled.