CHICAGO – The molecule of the moment – an experimental immunotherapeutic agent known as anti-PD-1 – appears to have encouraging activity against renal cell carcinoma in early clinical studies, an investigator reported at the annual meeting of the American Society of Clinical Oncology.
Nine of 33 patients (27%) with metastatic renal cell carcinoma (RCC) in a phase I trial had clinical responses to the agent, officially named BMS-936558, reported Dr. David F. McDermott, a hematologist/oncologist at Beth Israel Deaconess Medical Center in Boston.
Dr. David F. McDermott
The duration of responses ranged from more than 5.6 months to more than 22.3 months. More than half the patients (56%) had not progressed at 24 weeks.
"BMS-936558 can be administered safely in an outpatient setting to pretreated RCC patients, while demonstrating durable clinical benefit. Blockade of the PD-1 pathway may represent an important new target for RCC immunotherapy," Dr. McDermott said.
BMS-936558 is a monoclonal antibody that blocks the programmed death (PD)-1 receptor on the surface of activated T cells. Inhibition of the PD-1 and the PD-1 ligand (PD-L1) pathway rescues exhausted T-cells and enhances antitumor immunity.
When tested in a phase I trial, objective responses, defined as complete regression or significant partial regression, were reported in 18%-28% of 236 evaluable patients.
Serious side effects were observed in 14% of the 296 patients in the entire cohort, said Dr. Suzanne Topalian, director of the melanoma program and professor of surgery and oncology at Johns Hopkins University in Baltimore, who presented the results of the main study at the ASCO meeting. Dr. McDermott presented the results for patients with metastatic RCC in a separate session.
Patients with advanced RCC and other tumor types who had disease progression after 1-5 cycles of systemic therapies received the anti-PD-1 agents at varying doses until disease progression or clinical deterioration or unacceptable toxicity. Patients who had either a complete or partial response or stable disease, or had progressive disease but were clinically stable, were treated until they achieved a complete response, worsening progressive disease, or unacceptable toxicity for up to 12 cycles (96 weeks).
A total of 16 patients with RCC were enrolled at a 10 mg/kg dose of BMS-936558, and 17 were later enrolled at 1 mg/kg. Dr. McDermott presented safety data for those patients and another patient who was not available for an efficacy analysis but had available safety data.
Among patients on the 1-mg/kg dose, four (24%) had a response, with responses lasting from 5.6 to 17.5 months. All of these patients had stable disease for at least 24 weeks, and 47% of the group was progression free at 24 weeks. Median overall survival for this 1-mg/kg group has not been reached, precluding an analysis of overall survival for the entire cohort, "but it’s safe to say that it’s at least going to be 6 months," Dr. McDermottt said.
In the 10-mg/kg group, the overall response rate was 31%; two patients with a persistent reduction in baseline target lesions in the presence of new lesions were not counted as responders in the analysis, he noted.
The responses lasted from 8.4 to 22.3 months, and about two-thirds of the group were progression free at 24 weeks.
"In the RCC patients, this agent was generally tolerable in the outpatient setting, with a safety profile that was similar to the total treated population," Dr. McDermott said.
Dr. Lauren C. Harshman
Grade 3 or 4 adverse events occurred in 6 patients (18%) with RCC.
"I think all in all, the tolerability and the intriguing preliminary efficacy support the ongoing studies of PD-1 blockade in RCC, and I think what makes the pathway especially interesting is whether we can use tumor PDL-1 expression as an upfront selection criterion," commented Dr. Lauren C. Harshman, an oncologist at Stanford (Calif.) University. Dr. Harshman was the invited discussant but was not involved in the study.
The trial received support from Bristol-Meyers Squibb and Ono Pharmaceutical Company. Dr. McDermott disclosed having received research funding from BMS, maker of the anti-PD-1 compound, and serving in a consulting or advisory role to the company. Dr Harshman disclosed receiving research funding from BMS.