Novel PD-1 antibody induced response in previously treated NSCLC

Patients with previously treated, advanced non–small cell lung cancer treated with the novel agent MK-3475 demonstrated durable objective responses, according to study results presented at the AACR-IASLC Joint Conference on the Molecular Origins of Lung Cancer.

The treatment also appeared well tolerated, researchers said.

Edward B. Garon

“Previously treated lung cancers are generally managed with chemotherapy, but unfortunately, the response rates and OS are quite low; therefore, there is a significant unmet need for new treatment options,” researcher Edward B. Garon, MD, assistant professor of medicine at the David Geffen School of Medicine at the University of California, said in a press release. “A significant percentage of patients with growing disease after two prior treatments had substantially reduced tumor volume in response to MK-3475, and the potential of this antibody drug to induce long-lasting responses in these patients is certainly exciting and promising.”

Garon and colleagues evaluated MK-3475 (Merck) — a humanized, monoclonal immunoglobulin G4 anti-PD-1 antibody — in 38 patients who had received at least two prior systemic regimens (median age, 63 years; range, 34-85 years).

Among the cohort, 42% were men and 42% had an ECOG performance status of 0. Researchers identified mutated EGFR in eight patients, mutated KRAS in six patients and rearranged ALK in two patients.

The patients received 10 mg/kg MK-3475 every 3 weeks and underwent tumor imaging every 9 weeks until disease progression.

At 9 weeks, the objective response rate — assessed using immune-related response criteria (irRC) — was 24%. RECIST-defined response was 21%.

Among patients with irRC-defined response, the median duration of response had not been reached at 62 weeks. Seven of these patients were still receiving treatment at the time of the last follow-up.

Researchers also identified PD-L1 protein expression in the tumors of 33 patients at baseline. Of them, the protein level was greater than the cutoff point in nine patients and lower in 24 patients.

Patients with PD-L1 expression greater than the cutoff demonstrated a 67% irRC response rate and a 57% RECIST response rate, whereas patients with expression levels lower than the cutoff demonstrated a 4% irRC response rate and a 9% RECIST response rate.

Most patients (53%) experienced a drug-related adverse event. The most common adverse events were rash (21%), pruritus (18%) and fatigue (16%).

One patient (3%) developed grade 3 pulmonary edema.

“Hopefully our data will be confirmed in larger studies and, as a result, provide more treatment options for patients with this difficult-to-treat disease,” Garon said.

For more information:

Garon EB. Abstract #A20. Presented at: AACR-IASLC Joint Conference on the Molecular Origins of Lung Cancer; Jan. 6-9, 2014; San Diego.

Disclosure: The study was funded by Merck.