FDA Decision Nears for Pembrolizumab in Lung Cancer

Jean-Charles Soria, MD

Jean-Charles Soria, MD

In a 2015 European Cancer Congress (ECC) presentation, data from the pivotal KEYNOTE-001 trial showing pembrolizumab’s efficacy in pretreated non—small cell lung cancer (NSCLC) were presented just days before the FDA is scheduled to make its approval decision on the PD-1 inhibitor in this setting (October 2, 2015).

“We observed similar efficacy and safety across the two doses of pembrolizumab, supporting a dose of 2 mg/kg every 3 weeks as an effective dose in non—small cell lung cancer,” said presenter Jean-Charles Soria, MD. “A PD-L1 tumor proportion score of 50% or greater identifies patients with the greatest likelihood of clinical benefit. Patients with higher PD-L1 expression may have a faster time to response.”

The data showed that almost 30% of previously treated NSCLC patients with elevated PD-L1 expression had objective responses with 2 mg/kg of pembrolizumab (Keytruda). The response rate increased to 40% with a dose of 10 mg/kg. Response rates declined with lower levels of PD-L1 expression, said Soria, who is a medical oncologist at Institut Gustave Roussy in Villejuif, France.

The phase I KEYNOTE-001 included 495 previously treated and treatment-naïve patients with advanced or metastatic NSCLC. The data Soria presented at the ECC involved only the subset of 449 previously treated patients.

The trial was divided into two stages. During the nonrandomized stage, investigators studied the safety and efficacy of pembrolizumab at 10 mg/kg administered every 3 weeks or every 2 weeks. The evaluation included three cohorts and a combined total of 114 patients with PD-L1—positive and negative tumors.

The randomized stage of the study involved 280 patients, who were allocated to 10 mg/kg of pembrolizumab administered every 3 weeks or every 2 weeks. Finally, investigators validated the 2 mg/kg dose, administered every 3 weeks, in a nonrandomized study involving 55 patients.

The patients had a median age of 62 to 63, even distribution between men and women, and 82% nonsquamous histology. A majority (53%) of the 394 patients treated at the 10 mg/kg dose had received three or more prior lines of therapy, as compared with 36% of the patients treated with 2 mg/kg.

Soria said 74.2% of patients with PD-L1 levels of at least 50% had some degree of tumor reduction with pembrolizumab, as compared with 51.7% of patients who had less than 50%.

The overall response rate was about 19% in patients treated with 2 mg/kg or 10 mg/kg of pembrolizumab. The response rate increased with increased PD-L1 expression in patients treated with either dose.

Survival data for all patients treated with the 10 mg/kg dose showed a median overall survival of 11.3 months and median progression-free survival (PFS) of 3.0 months. Survival increased to a median of 15.5 months in the subgroup of patients with PD-L1 expression ≥50%, and median PFS increased to 5.8 months in this group.

The 6-month survival was 63% in all patients treated with 10 mg/kg of pembrolizumab and 71.6% for PD-L1—positive patients. The 6-month PFS increased form 34.0% for all patients to 49.9% for those with PD-L1 levels ≥50%.

The ongoing phase II/III randomized KEYNOTE-010 trial is comparing pembrolizumab at 2 mg/kg and 10 mg/kg, both administered every 3 weeks, against docetaxel in patients with previously treated NSCLC (NCT01905657).

The current FDA review of the PD-1 inhibitor is specifically for treating patients with advanced NSCLC across all histologies whose disease has progressed on or after platinum-containing chemotherapy, as well as a targeted agent inEGFR- orALK-positive patients. A final approval decision is scheduled to be made by October 2. The priority review follows a breakthrough therapy designation for pembrolizumab in this setting that was granted by the FDA in October 2014.

Soria JC, Fløtten Ø, Horn L, et al. Efficacy and safety of pembrolizumab (Pembro; MK-3475) for patients (Pts) with previously treated advanced non-small cell lung cancer (NSCLC) enrolled in KEYNOTE-001. Presented at: 2015 European Cancer Congress; September 25-29; Vienna, Austria. LBA 33.