Phase I Study Successfully Targets Metastatic Kidney Cancer Interview with:

Kevin D. Courtney, M.D., Ph.D.  Assistant Professor UT Southwestern Medical Cente

Dr. Courtney

Kevin D. Courtney, M.D., Ph.D. 
Assistant Professor
UT Southwestern Medical Center What is the background for this study? What are the main findings?

Response: Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer. Metastatic ccRCC does not respond to traditional chemotherapy.

Current standard treatments for metastatic ccRCC include drugs called vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) that block the growth of new blood vessels that feed the cancer, as well as drugs that inhibit an enzyme called mTOR that is involved in ccRCC growth and immune therapies that rev up the body’s immune response to try to fight the cancer. Each of these treatments can have significant side effects for patients that can make them difficult to tolerate.

Metastatic ccRCC is largely incurable, and we need novel and better-tolerated treatments. A central driver of ccRCC is a protein called hypoxia inducible factor 2alpha (HIF-2alpha). This protein has been very difficult to try to target with a drug. This study is the first to test a drug that targets HIF-2alpha in patients with metastatic ccRCC. The study results showed that the HIF-2alpha inhibitor, PT2385 (Peloton Therapeutics) was active in fighting metastatic ccRCC and was well-tolerated. What should clinicians and patients take away from your report?

Response: PT2385 is the first drug that targets HIF-2alpha, a protein that is a central driver of the most common form of kidney cancer, and in doing so benefited patients with metastatic kidney cancer and was safe to administer. What recommendations do you have for future research as a result of this study?

Response: Further testing of HIF-2alpha inhibitors, either by themselves or in combination with other anti-cancer drugs like the VEGFR TKIs or immune therapies described above, is warranted to try to advance our treatment of patients with metastatic kidney cancer and perhaps other types of cancer as well. Is there anything else you would like to add?

Response: UT Southwestern Medical Center owns stock in Peloton Therapeutics and has a financial interest in the clinical trial described in the article. Thank you for your contribution to the community.


J Clin Oncol. 2017 Dec 19:JCO2017742627. doi: 10.1200/JCO.2017.74.2627. [Epub ahead of print]

Phase I Dose-Escalation Trial of PT2385, a First-in-Class Hypoxia-Inducible Factor-2α Antagonist in Patients With Previously Treated Advanced Clear Cell Renal Cell Carcinoma.

Courtney KD1, Infante JR1, Lam ET1, Figlin RA1, Rini BI1, Brugarolas J1, Zojwalla NJ1, Lowe AM1, Wang K1, Wallace EM1, Josey JA1, Choueiri TK1.

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Last Updated on January 1, 2018 by Marie Benz MD FAAD