Monoclonal Antibody Shown to Shrink Various Types of Tumors

Bristol-Myers Squibb’s investigational drug facilitates improved immune response in lung cancer, kidney cancer, and melanoma patients, according to a study presented at the American Society of Clinical Oncology (ASCO).

The use of a human monoclonal antibody called BMS-936558 was shown in trials to significantly shrink tumors in 18% of non small-cell lung cancer (NSCLC) patients, 28% of metastatic melanoma patients, and 27% of those with renal cell carcinoma (RCC), according to research presented at the American Society of Clinical Oncology (ASCO) this past week.

The investigational drug works by allowing T cells to function properly, thereby strengthening the immune system. Cancer cells often have the ability to turn off the immune response by releasing a protein called PD-L1, which can bind to PD-1 (also known as programmed death 1) on the surface of activated T cells. When these two proteins are joined together, the T cell dies or becomes inactive, losing the ability to effectively attack tumor cells.

BMS-936558 is an antibody that blocks the activity of the PD-1 receptor on immune cells and prevents PD-1 and PD-L1 from binding.

The phase I trial enrolled 296 patients who already had been heavily treated for melanoma, colorectal, NSCLC, prostate, or RCC. Participants received the drug intravenously in an outpatient setting every 2 weeks of each 8-week treatment cycle.

Overall, the adverse event profile was favorable, although there were three treatment-related deaths due to lung inflammation. In addition, the drug did not appear to work for a small number of patients with prostate cancer or colon cancer.

In cases where tumors did shrink, many did not grow back again for more than a year, according to the study’s lead author, Suzanne L. Topalian, MD, professor of surgery and oncology at Johns Hopkins University.

Preliminary data implicate PD-L1 expression on tumor cells as a potential predictive biomarker of response, according to study authors. “Results from this phase 1 study of anti-PD-1 showed clinical activity across NSCLC, metastatic melanoma, and RCC, adding to our scientific understanding of the potential of immune-oncology as a therapeutic approach in the treatment of cancer,” said Thomas J. Lynch, Jr., MD, director of Yale Cancer Center and physician-in-chief of The Smilow Cancer Hospital at Yale-New Haven, which was involved in the clinical trials.

Watch the below video from OncLive to hear Suzanne L. Topalian, MD, discuss the early-stage results of BMS-936558: