Pembrolizumab Granted Priority Review for NSCLC

Roger Perlmutter, MD, PhD

Roger M. Perlmutter, MD, PhD

The FDA has granted a priority review to pembrolizumab (Keytruda) as a potential treatment for patients with advanced non-small cell lung cancer (NSCLC) following treatment with chemotherapy or a targeted therapy, if applicable.

The priority review and a prior breakthrough therapy designation for patients with NSCLC were based on results from the phase I KEYNOTE-001 trial. In this study, pembrolizumab had an ORR of nearly 20% among 495 previously treated and treatment-naïve patients with advanced or metastatic NSCLC. The ORR was 45.2% among a cohort of patients with high PD-L1—expressing NSCLC. The FDA is scheduled to make a decision on the application by October 2, 2015.

“Today’s announcement reflects our commitment to accelerate the development of immunotherapeutic approaches to treat lung cancer, one of the most deadly malignancies," Roger M. Perlmutter, MD, president of Merck Research, said in a statement. "We believe that data submitted to the FDA illustrate the significant potential of Keytruda to treat advanced non—small cell lung cancer—and we look forward to working with the FDA to bring our anti–PD-1 therapy to patients afflicted with this devastating cancer.”

The KEYNOTE-001 trial included 495 previously treated and treatment-naïve patients with advanced or metastatic NSCLC. The total population comprised a training set of 182 patients and a validation set of 313 patients. Pembrolizumab was administered at three dosages: 2 mg/kg every 3 weeks, 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks. The researchers assessed patient responses every 9 weeks.

Results from the KEYNOTE-001 study were presented at the 2015 AACR Annual Meeting and simultaneously published online in TheNew England Journal of Medicine.

In the entire study population, the ORR was 19.4% and median overall and progression-free survival were 12.0 and 3.7 months, respectively. The median duration of response was 12.4 months.

In the validation group, researchers were able to evaluate PD-L1 expression in 204 patients using an IHC clinical trial assay (CTA). Patients were divided into three groups, based on whether they had membranous PD-L1 expression in their tumor cells of &ge;50% (n = 73), 1%-49% (n = 103), or <1% (n = 28).

ORR in the three groups was 45.2%, 16.5%, and 10.7%, respectively. The results were comparable but slightly better among patients who had not received prior therapy versus those who were previously treated.

Survival data were also presented at AACR for 356 patients in the total population whose PD-L1 levels were evaluable by the CTA. After a median follow-up of 10.9 months, OS was not yet reached in the high PD-L1 group (n = 119) and was 8.8 months in both the intermediate (n = 161) and low (n = 76) PD-L1 groups. PFS was 6.3, 3.3, and 2.3 months in the three groups, respectively. The duration of response was similar in the three cohorts at 12.4 months, 10.3 months, and not yet reached.

Overall, pembrolizumab was considered tolerable. Grade &ge;3 adverse events occurred in 9% of patients. Immune-related adverse events reported in &ge;2% of the population included pneumonitis, hypothyroidism, and infusion reactions. Pneumonitis was the cause of the one treatment-related death in the study.

&ldquo;These results have the potential to substantively change the way that lung cancer is treated,&rdquo; KEYNOTE-001 lead author, Edward Garon, MD, said when the results were presented. &ldquo;The effectiveness of pembrolizumab in treating patients with NSCLC and the prolonged duration of their responses is quite exciting,&rdquo; added Garon, who is medical director of Thoracic Oncology at UCLA&rsquo;s Jonsson Comprehensive Cancer Center.