Overview

This trial is active, not recruiting.

Condition renal cell carcinoma
Treatments axitinib, mk-3475
Phase phase 1
Targets PD-1, VEGF, PDGF
Sponsor Pfizer
Collaborator Merck Sharp & Dohme Corp.
Start date September 2014
End date March 2017
Trial size 60 participants
Trial identifier NCT02133742, A4061079

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Masking open label
Primary purpose treatment
Arm
(Experimental)
To test the maximum tolerated dose of MK-3475 at 2 mg/kg every three weeks intravenous infusion in combination with approved axitinib dose
axitinib
Axitinib at starting dose of 5 mg and 3 mg BID.
mk-3475
MK-3475 with two dose levels: 2 mg/kg every three weeks to find the maximum tolerated dose and continue treatment in a dose expansion phase.

Primary Outcomes

Measure
Number of participants with Dose-limiting toxicities (DLT)
time frame: Baseline up to 6 weeks

Secondary Outcomes

Measure
Duration of Response (DR)
time frame: 18 months
Percentage of Participants With Objective Response
time frame: 18 months
Progression-Free Survival (PFS)
time frame: 18 months
Overall Survival (OS)
time frame: five years
Maximum Observed Plasma Concentration (Cmax)
time frame: up to 2.5 years
Time to Reach Maximum Observed Plasma Concentration (Tmax)
time frame: up to 2.5 years
Apparent Oral Clearance (CL/F)
time frame: up to 2.5 years
Immunogenicity
time frame: Up to 2.5 years
Eastern Cooperative Oncology Group [ECOG] performance status
time frame: Up to 2.5 years
Presence (rate) or absence of blood biomarkers
time frame: Up to 2.5 years

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title 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
Trial information was received from ClinicalTrials.gov and was last updated in December 2016.
Information provided to ClinicalTrials.gov by Pfizer.