Phase II Study of KW2871 Combined With High Dose Interferon-α2b in Patients With Metastatic Melanoma
Condition: Metastatic Melanoma; Cutaneous Melanoma
MeSH terms: Melanoma
Intervention: HDI; KW2871; KW2871; KW2871
Intervention description: 20 MU/m^2 IV QD for 5 days/week for 4 weeks, then 10 MU/m^2 SC 3 days/week until disease progression; 5 mg/m^2 IV every 2 weeks until disease progression; 10 mg/m^2 IV every 2 weeks until disease progression; 20 mg/m^2 IV every 2 weeks until disease progression
Intervention MeSH terms: Interferons; Ecromeximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Dose-escalation cohorts
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: KW2871; Ecromeximab; Anti-ganglioside; Antibody; Interferon alpha; Metastatic melanoma

Summary:

      This was a Phase 2, open-label study of KW2871 (ecromeximab) in combination with high-dose
      interferon-α2b (HDI) in patients with metastatic melanoma. The primary objectives of this
      study were to assess progression-free survival (PFS) and safety. The secondary objectives
      were to assess the objective response rate, KW2871 pharmacokinetics (PK), and other
      exploratory immunology as indicated (e.g., development of human anti-chimeric antibodies
      [HACA], activity of antibody-dependent cell-mediated cytotoxicity [ADCC] and
      complement-dependent cytotoxicity [CDC] in peripheral blood, number and functional state of
      tumor-infiltrating immune cells and expression of GD3 in immune and tumor cells of tumor
      biopsies, and markers of interferon [IFN] response/resistance and markers of resistance to
      ADCC/CDC in peripheral blood mononuclear cells [PBMCs]).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age ≥ 18 years of age.

          2. Histologically proven metastatic cutaneous, mucosal, or unknown primary melanoma.

          3. Measurable disease using Response Evaluation Criteria in Solid Tumors (RECIST).

          4. Ambulatory (Eastern Cooperative Oncology Group [ECOG] performance status 0 or 1) or
             expected survival ≥ 4 months.

          5. Within the last 2 weeks prior to study day 1, the following laboratory parameters
             within the ranges specified:

               -  Hemoglobin: ≥ 9 g/dL

               -  Platelets: ≥ 100 x 10^9/L

               -  Neutrophils: ≥ 1.5 x 10^9/L

               -  International normalized ratio: ≤ 2.0 (≤ 3.0 if on warfarin therapy)

               -  Serum creatinine: ≤ 1.5 x upper limit of normal (ULN)

               -  Serum total bilirubin: ≤ 1.5 x ULN

               -  Aspartate aminotransferase/alanine aminotransferase: ≤ 2.5 x ULN

          6. Able and willing to give valid written informed consent.

        Exclusion Criteria:

          1. Other malignancy within 3 years prior to study entry for which the patient received
             active treatment, except for treated melanoma or non-melanoma skin cancer, cervical
             cancer, and breast carcinoma in situ.

          2. Mental impairment that may have compromised the ability to give informed consent and
             comply with the study requirements.

          3. Participation in any other clinical trial involving chemotherapy, radiotherapy, or
             other immunotherapy within 4 weeks prior to study enrollment.

          4. Prior exposure to anti-GD3 antibodies.

          5. Pregnancy or breastfeeding.

          6. Women of childbearing potential who refused or were unable to use effective means of
             contraception.

          7. Active autoimmune or other disorders that required systemic treatment with
             immunomodulatory or immunosuppressant medications (i.e., corticosteroids,
             cyclophosphamide, methotrexate, other biologics). Corticosteroids at substitution
             doses were allowed.

          8. Metastatic brain disease was allowed provided that appropriate treatment had been
             administered (surgery or irradiation) and 2-month follow-up by brain magnetic
             resonance imaging (MRI) showed disease control (stability or regression).

          9. Autoimmune-related hypothyroidism and vitiligo-like depigmentation were allowed
             provided the patient was medically stable with treatment (thyroid-hormone replacement
             or observation).

         10. Serious medical illness, such as cardiovascular disease (uncontrolled congestive heart
             failure or hypertension, active ischemic disease of the heart [angina], recent [<3
             months] myocardial infarction, severe cardiac arrhythmia), bleeding disorders,
             obstructive or restrictive pulmonary diseases, active systemic infections requiring
             antibiotics, serious intercurrent illness requiring hospitalization, inflammatory
             bowel disorders, or significant psychiatric disease, which in the opinion of the
             principal investigator would have prevented adequate informed consent or rendered
             study treatment unsafe or contraindicated.

         11. Patients with clinical suspicion of human immunodeficiency virus (HIV) or hepatitis
             underwent the following viral tests: patients with HIV must have had negative
             antibodies; patients with hepatitis B virus must have had negative antigens; patients
             with hepatitis C virus must have had a negative test for serum antibodies. If any of
             the tests were positive, patients were excluded from the study.