A Phase 1 Multicenter Open-label Study to Evaluate the Safety Tolerability and PK of MEDI0680 (AMP-514) in Subjects With Advanced Malignancies

Inclusion criteria

• At least 18 years of age at time of study entry
• Written informed consent and any locally required authorization (eg, Health Insurance Portability and Accountability Act [HIPAA] in the USA) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations
• Histologically- or cytologically-confirmed melanoma or clear-cell RCC that are refractory to standard therapy or for which no standard therapy exists

• Subjects must have failed, be intolerant to, or be ineligible for any potentially curative approved treatment, irrespective of line of therapy
• No more than 3 prior lines of therapy
• At least 1 measurable lesion per RECIST v1.1; subjects whose only measurable lesion is a lymph node will be excluded
• Eastern Cooperative Oncology Group performance score of 0 or 1
• For all tumor types, adequate organ and marrow function, as defined below:

• Hemoglobin ³ 9.0 g/dL within first 2 weeks prior to first dose of MEDI0680 (AMP-514)
• Absolute neutrophil count (ANC) ³ 1.5 × 109/L (1,500/mm3)
• Platelet count ³ 100 × 109/L (100,000/mm3)
• Total bilirubin ≤ 1.5 × ULN except subjects with documented Gilbert's syndrome (> 3 × ULN) or liver metastasis, who must have a baseline total bilirubin ≤ 3.0 mg/
• Alanine aminotransferase and AST ≤ 2.5 × ULN; for subjects with hepatic metastases, ALT and AST ≤ 5 × ULN
• Serum creatinine ≤ 1.5 × ULN OR calculated creatinine clearance (CrCl) or 24-hour urine CrCl ≥ 50 mL/minute ▪ Cockcroft-Gault formula will be used to calculate CrCl; 24-hour urine CrCl will be derived using the measured creatinine clearance formula
• Prior treatment toxicities must be ≤ Grade 1

Exclusion criteria

• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study
• Receipt of any BRAF inhibitor (in metastatic melanoma), or investigational anticancer therapy within 4 weeks prior to the first dose of MEDI0680 (AMP-514)
• Prior exposure to immunotherapy, such as, but not limited to, other anti-CTLA-4, anti-PD-1, or anti-PD-L1 antibodies, excluding therapeutic cancer vaccines
• Major surgery (as defined by the investigator) within 4 weeks prior to first dose of MEDI0680 (AMP-514) or still recovering from prior surgery
• Other invasive malignancy within 2 years except for noninvasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured
• Prior allogeneic or autologous bone marrow or organ transplantation that requires use of immunosuppressives
• Unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE v4.03 Grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria with the exception of alopecia. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by MEDI0680 (AMP-514) may be included (eg, hearing loss) after consultation with the MedImmune medical monitor
• Active or prior documented autoimmune disease within the past 2 years