Results from an early-stage study show that treatment with the investigational drug BMS-936558 caused tumor shrinkage in up to a quarter of patients with advanced melanoma, kidney and non-small cell lung (NSCLC) cancers. This antibody drug targets a key pathway in T-cells (white blood cells that help fight infection and cancer) called PD-1, which inhibits the body’s immune response to cancer. By blocking this pathway, BMS-936558 may re-activate the immune system to fight tumor cells.
“It’s exciting to see this degree of anti-tumor activity from a single agent among patients with a range of cancers that had progressed despite standard therapies,” said Suzanne Topalian, MD, Professor of Surgery and Oncology at the Johns Hopkins University School of Medicine. “We were especially surprised to see activity in nearly 20 percent of patients with lung cancer, who are historically unresponsive to immune-based therapies. These findings mark what is probably the strongest anti-lung cancer activity observed to date with any immunotherapy.”
This Phase I trial with expansion cohorts enrolled 296 patients with melanoma, colorectal, NSCLC, prostate and renal cancer that had progressed despite standard therapies. Responses were observed in patients with melanoma (26/94 patients; 28%), renal cancer (9/33 patients; 27%), and NSCLC (14/76 patients; 18%). Responses were seen both in patients with squamous and non-squamous cell subtypes of lung cancer. Many patients responded for 12 months or longer and had ongoing responses at the time of this report.
The drug was generally well-tolerated; serious toxicities were observed in 14 percent of patients. Side effects were generally consistent with those seen in other immune-focused therapies for cancer.
A sub-analysis of data from the trial also hints at a potential biomarker on cancer cells – a protein called PD-L1 – that could help predict which patients will respond to BMS-936558. Investigators analyzed tumor samples obtained from 42 patients prior to treatment initiation, for expression of the PD-L1 protein on the surface of tumor cells. After correlating the results with response data, they noted that over one-third of patients with PD-L1 positive tumors responded to the drug (9/25 patients; 36%), while none of the 17 PD-L1 negative patients had a response. Additional studies are planned to further assess the potential role of PD-L1 as a predictive marker of response to anti-PD-1 therapy.
Title: Anti-PD-1 (BMS-936558, MDX-1106) in patients with advanced solid tumors: Clinical activity, safety, and a potential biomarker for response.