Evaluation of Biomarkers Predictive of Benefit from the PD-1 Inhibitor MK-3475 in Patients with Non-Small Cell Lung Cancer and Brain Metastases
Abstract
Rationale and Objective: Approximately 30% of patients with non-small cell lung cancer (NSCLC) at some point in their disease course have cancer that has spread to the brain. These patients on average have a shorter life span and limited treatment options compared to patients without cancer in the brain. Unfortunately, many clinical trials do not allow such patients or they require treatment such as surgery or radiation to the brain prior to starting the trial therapy, which can cause significant and long-lasting side effects. Recently there have been several very promising drugs developed for lung cancer that target the immune system. These immunotherapies act to allow the patient s own immune system to attack the cancer and appear to work extremely well for long periods of time in some patients with NSCLC. However, there is still much to learn about these drugs so that they have the most benefit for patients with lung cancer. First, we do not know whether they work in patients who have lung cancer in the brain. Second, there is no definite test that tells doctors who will benefit from immunotherapy. To address these issues, we have started a clinical trial using the immunotherapy pembrolizumab (MK-3475) for patients with lung cancer that has spread to the brain. The objective of this study is to determine how to identify patients with lung cancer and untreated cancer in the brain who are most likely to benefit from immunotherapy. This addresses the Lung Cancer Research Program Areas of Emphasis in that it aims to establish biomarkers predictive of treatment response and enables us to understand susceptibility and resistance to treatment. To achieve our objective, we will first study tumors from patients with lung cancer who have multiple samples available from different parts of the body and will determine if markers differ based on where the biopsy is taken: the primary lung tumor, another site of cancer, and cancer in the brain. If we find that there is a difference, this may lead us to obtain biopsies from only a certain site of cancer in the future. Next, we will obtain tumor biopsies and blood samples from patients on our clinical trial with the immunotherapy pembrolizumab and will determine whether certain markers on the tumor or in the blood correlate with how well the treatment works. If we find specific markers on the tumors or in the blood of patients that respond well to treatment, this may lead us in the future to test for these markers in order to decide which patients to treat with immunotherapy. Career Goals: Dr. Goldberg is an Assistant Professor of Medicine at the Yale Cancer Center. She completed a medical oncology fellowship that included both clinical and research training. Her career goal is to conduct lung cancer clinical and translational research in novel therapeutics and biomarker development with the objective of identifying improved treatment strategies to increase survival from this deadly disease. Her formal training and research experience create a strong foundation on which to build a research career. The Career Development Plan in this proposal includes devoting a significant proportion of time to research at this early stage in her career to allow for the experience necessary while in a mentored setting. It also provides the ability to undergo formal training in laboratory techniques and to receive hands-on experience designing and executing experiments in a laboratory setting. Providing her with the time to dedicate to this project including the laboratory experience and formal research training will allow her to focus on the scientific aspects of translational research, which will strengthen her overall research abilities. Applicability: Our hope is that this work will help us know in advance which patients will do well with immunotherapy so that they have better access to these drugs and also which patients will not benefit so that they can avoid this treatme
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510203
Entities
People
- Sarah Goldberg
Organizations
- United States Army
- Yale University