Phase I Study of Single Agent Pembrolizumab MK-3475 in Patients with Progressive Locally Advanced or Metastatic Carcinomas, Melanoma and Non-Small Cell Lung Carcinomas, (Keynote 001)
There are 5 parts to this clinical research study. MD Anderson will be taking part in Parts B, D, and F. This consent form will cover Parts B, D, and F. The goal of Part B is to further test the highest tolerable dose of MK-3475 (pembrolizumab) that was found in Part A when given to patients with melanoma. The safety of this drug will also be studied. The goal of Part D is to study 2 dose levels of pembrolizumab when given to patients with melanoma. The goal of Part F is to study 2 dose levels of pembrolizumab when given to patients with lung cancer. Pembrolizumab is a drug that includes a protein naturally created by living cells. It is designed to help the body's natural defense system react against tumors by blocking proteins that cancers cells create to "turn off" the body's immune (defense) system.
Treatment Location: N/A
Primary Objectives: 1) To evaluate and characterize the tolerability and safety profile of single agent MK-3475 in adult patients with unresectable advanced carcinoma including non-small cell lung cancer (NSCLC or melanoma (MEL). 2) To evaluate anti-tumor activity of MK-3475 in MEL and NSCLC per RECIST 1.1 3) To evaluate the extent of tumor response that correlates with the degree of biomarker positivity in the tumors of ipilimumab naive patients treated with MK-3475 with the intent that the cut point for the PD-L1 assay willb e explored and refined with tumor samples from ipilimumab-naive MEL. 4) To evaluate anti-tumor activity per RECIST 1.1 of MK-3475 in unselected MEL refractory to ipilimumab patients and MEL patients refractory to ipilimumab with PD-L1 expressing tumors. 5) To evaluate anti-tumor activity per RECIST 1.1 of MK-3475 in patients with NSCLC with at least one prior systemic therapy whose tumors express a high level of PD-L1. Secondary Objectives: 1) To evaluate the RR of unselected patients with MEL refractory to ipilimumab and MEL naïve to ipilimumab, patients with MEL refractory to ipilimumab and MEL naïve to ipilimumab whose tumors express PD-L1, and patients with NSCLC with at least one prior systemic therapy whose tumors express a high level of PD-L1, per immune-related response criteria. 2) To characterize the PK profile of single agent MK-3475. 3) To evaluate target engagement and modulation in peripheral blood program cell death-1 (PD-1) receptor occupancy and modulation of receptor activity. 4) To investigate the relationship between candidate efficacy biomarkers and anti-tumor activity of MK-3475: To evaluate the correlation between PD-L1 expression levels and anti-tumor activity of MK-3475 in patients with melanoma, excluding ipi-refractory patients as stated in the primary objectives, and separately, non-small cell lung cancer. To investigate other biomarkers (e.g., tumor infiltrating lymphocytes, PD-L2, PD-1 ribonucleic acid (RNA) signature profiles) that may correlate with tumor responses. To evaluate differences in tumor tissue characteristics in biopsies taken during or post-treatment with MK-3475 versus baseline. 5) To evaluate response duration, progression-free-survival and overall survival of MEL patients who are treated with MK-3475. 6) To evaluate response duration, progression-free survival and overall survival of NSCLC patients who are treated with MK-3475. Tertiary Objectives: To examine concordance between archival tumor tissues, formalin-fixed, paraffin embedded tissue (FFPET) and newly obtained frozen tumor tissue with respect to PD-L1 expression and other candidate efficacy biomarkers.
IRB Review and Approval Date: 03/06/2012
Recruitment Status: Closed
Projected Accrual: N/A
Information and next steps
Melanoma Medical Oncology
For general questions about clinical trials: