A Dose Finding Study To Evaluate Safety, Drug Interaction, Tumor Markers Of Axitinib In Combination With MK-3475 In Adult Patients With Previously Untreated Advanced Renal Cell Cancer

A PHASE 1B, OPEN LABEL, DOSE FINDING STUDY TO EVALUATE SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS OF AXITINIB (AG-013736) IN COMBINATION WITH PEMBROLIZUMAB (MK-3475) IN PATIENTS WITH ADVANCED RENAL CELL CANCER

Despite substantial improvements of patients outcome in advanced RCC, durable and complete response is uncommon. The majority of patients eventually develop resistance and exhibit disease progression. Combining a PD-1 inhibitor, which has shown single-agent efficacy with axitinib may provide additional clinical benefit compared to axitinib alone.

Inclusion Criteria:

• Histologically or cytologically confirmed advanced RCC with predominantly clear-cell subtype with primary tumor resected
• At least one measureable lesion as defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
• Eastern Cooperative Oncology Group performance status 0 or 1
• Controlled hypertension

Exclusion Criteria:

• Prior treatment with systemic therapy for advanced RCC
• Prior adjuvant or neoadjuvant therapy if disease progression or relapse has occurred during or within 12 months after the last dose of treatment
• Prior treatment with any agent specifically targeting T-cell co-stimulation or checkpoint pathways
• Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis
• Diagnosis of any non-RCC malignancy occurring within 2 years prior to the date of randomization except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix or low grade prostate cancer with no plans for treatment intervention
• In past 12 months: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
• In past 6 months: deep vein thrombosis or pulmonary embolism