This article is more than 5 years old. Information may no longer be current.
Trial to assess novel therapeutic approach for kidney cancer
Click Here to Manage Email Alerts
Researchers at Dana-Farber Cancer Institute are testing a new treatment strategy designed to improve outcomes for patients with kidney cancer at high risk for recurrence after surgery, according to a press release.
The approach pairs a novel personalized vaccine with immunotherapy delivered in a new way.
“These are patients who have high-risk disease and have had the tumor surgically removed. There is no clear evidence of disease left in their body, but we know that up to half of them will eventually have disease recurrence resulting from undetected residual tumor cells,” David A. Braun, MD, PhD, fellow in medical oncology at Dana-Farber Cancer Institute and Brigham and Women’s Hospital, said in a press release. “Currently there are no good treatment options available for these patients to decrease the chances of recurrence.”
HemOnc Today spoke with Braun about the study, the need for more effective treatments in this setting, the timeline for results, and the implications of this approach if proven effective and safe.
Question: Can you explain the rationale for this study?
Answer: There is a tremendous clinical need to increase the effectiveness of immunotherapies in kidney cancer and decrease their immune-related toxicities. Kidney cancer is one of those diseases where, historically, a limited number of patients responded to the old style of cytokine immunotherapy. As we enter the modern era of immune checkpoint blockade, these are becoming the mainstay of therapy for kidney cancer. As promising as these therapies are, a substantial number of patients will not derive long-term benefit. These therapies also can be associated with immune-related adverse events. We wanted to see if we could increase the effectiveness of the immune response to specifically target a patient’s tumor. Rather than only ‘cutting the brakes’ with immune checkpoint blockade, we also hope to ‘steer’ the immune system directly toward the tumor using a personalized, tumor-specific vaccine.
Q: Can you elaborate on the need for more effective treatments in this setting?
A: There are unfortunately not a lot of good treatment options in this disease setting. There is one FDA-approved therapy for stage III kidney cancer — sunitinib (Sutent, Pfizer) — but it has not been shown to increase OS and can be accompanied by serious toxicities. Further, for patients with stage IV kidney cancer who have had their tumor removed surgically, there is really no standard-of-care therapy to reduce the risk for tumor recurrence.
Q: How will the study be conducted?
A: We chose to conduct the study in the adjuvant setting, including patients with high-risk kidney cancer who have had all of the tumor removed and no evidence of disease at the time of study. We sequence the tumor and blood to identify specific mutations of the tumor. With computational biology collaborators at Dana-Farber and the Broad Institute, we have a state-of-the-art bioinformatics pipeline where we hope to predict which of these mutations are most likely to stimulate the patient’s immune system to generate a response. We then manufacture a customized peptide vaccine for each patient, based on that patient’s mutations, and deliver the therapy. We are administering this vaccine in combination with the standard immune checkpoint inhibitor, ipilimumab (Yervoy, Bristol-Myers Squibb), but delivered in a new way — a local injection in the subcutaneous tissue at the vaccine site — with the hope that we can give a lower dose of the immune checkpoint inhibitor and steer the activated immune response specifically toward the tumor. The goal is to increase the specificity of the antitumor immune response in order to increase the effectiveness of immune-based therapy while decreasing adverse events.
Q: What is the anticipated timeline for results?
A: This is a proof-of-concept study that has never been done before in kidney cancer. We hope to accrue 15 patients within the next year. There are different endpoints we will want to follow, including safety, the ability to stimulate the immune system, and ultimately whether we are able to decrease the rate at which these patients relapse.
Q: What do you expect to find?
A: We first want to see that this approach is safe, and we have strong reason to believe that it will be. In other cohorts of patients with melanoma and glioblastoma, a similar personalized vaccine approach was very safe. We also hope this treatment will generate a proper immune response and prevent relapse.
Q: What are the implications if this approach is proven effective and safe?
A: There are a lot of potential implications, but it is important to take this one step at a time and first prove that this is a safe approach. Ultimately, we hope that this trial — together with future studies — will help develop a novel, safe and effective tool in the armamentarium against kidney cancer. – by Jennifer Southall
For more information:
David A. Braun, MD, PhD, can be reached at Dana-Farber Cancer Institute, DA518, 450 Brookline Ave., Boston, MA, 02215; email: david_braun@dfci.harvard.edu.
Disclosure: Braun reports no relevant financial disclosures.