Ipilimumab vs Ipilimumab Plus Nivolumab in Patients With Stage III-IV Melanoma Who Have Progressed or Relapsed on PD-1 Inhibitor Therapy

Main Inclusion Criteria:

• American Joint Committee on Cancer (AJCC) (2009) Stage IV cutaneous melanoma or Stage III cutaneous, acral or mucosal melanoma that is judged inoperable. Patients with a history of uveal melanoma are not eligible.
• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with computerized tomography (CT) scan. Patients must have at least one measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) and a separate lesion amenable to biopsy.
• Histologic proof of melanoma reviewed and confirmed by the enrolling site.
• Previous treatment with a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor with documented progression of disease on most recent CT scan. Progression of disease is defined as 1) the appearance of a new measureable lesion (>10 mm) on cross-sectional imaging or physical examination OR 2) enlargement of previously detected lesions on two consecutive imaging studies OR 3) enlargement of a previously detected lesion with correlative symptomatology on one cross-sectional imaging study. Patients remain eligible if they had a previous response to a PD-1 inhibitor, including patients who had a complete response, partial response or stable disease (SD). Primary progressing patients are defined as those who received anti-PD-1 therapy within 2 months of study enrollment. Patients with relapsed disease are defined as those who received their last dose of PD-1 blocking antibody ≥2 months prior to enrollment.
• Patients who received adjuvant PD-1 therapy who then develop measurable disease are eligible. However, they must have received their last dose of PD-1/PD-L1 blockade within two months of enrollment in this study. They will be stratified with patients who have primary progressive disease.
• Life expectancy of greater than 3 months.
• Age ≥ 18 years old.
• Eastern Cooperative Oncology Group performance status = 0 or 1 or Karnofsky Performance Status equivalent.
• Patients must have adequate organ and marrow function as defined below:
• White blood cells >2, 000/microliter (mcL)
• Absolute neutrophil count >1,500/mcL
• Platelets >100,000/mcL
• Hemoglobin > 9.0 g/dL
• Total bilirubin ≤ 1.5 X institution's upper limit of normal
• Aspartate aminotransferase (serum glutamic oxaloacetic transaminase)/alanine aminotransferase (serum glutamic pyruvic transaminase) ≤ 2.5 X institution's upper limit of normal for patients with no concurrent liver metastases, OR ≤ 5 X institution's upper limit of normal for patients with concurrent liver metastases
• Serum creatinine 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted.
• Patients with history of any grade 4 toxicity during previous anti PD-1 treatment or history of Grade 3 or higher pneumonitis.
• Patients with a history of Grade ≥2 neuropathy.
• Prisoners or patients who are involuntarily incarcerated.
• Children under the age of 18.
• Patients who require hemodialysis.
• Patients with a history of allergy to study drug components or history of a severe hypersensitivity reaction to any monoclonal antibody.