FDA Grants Priority Review to Keytruda for Advanced Small Cell Lung Cancer

The U.S. Food and Drug Administration has accepted Merck‘s application seeking accelerated approval of Keytruda (pembrolizumab) for the treatment of advanced small cell lung cancer (SCLC) patients who failed at least two prior therapies.

The supplemental biologics license application — based on results from the Phase 1b KEYNOTE-028 trial (NCT02054806) and the ongoing KEYNOTE-158 Phase 2 (NCT02628067) trial — was granted priority review. The regulatory agency expects to reach a decision by June 17.

The prognosis of patients with SCLC, a cancer that appears almost exclusively in heavy smokers, is generally poor, with a median overall survival of eight to 12 months, and a two-year overall survival rate of 5 percent.

“There is a significant need for new treatment options for small cell lung cancer, which has a five-year survival rate of only six percent overall,” Jonathan Cheng, vice president of oncology clinical research at Merck Research Laboratories, said in a press release.

Keytruda, developed by Merck (known as MSD outside the U.S. and Canada), is a type of therapy called an immune checkpoint inhibitor. It binds to a protein called PD-1 on immune T-cells, blocking their binding to PD-L1 on tumor cells. Cancer cells use this interaction between PD-1 and PD-L1 to evade immune attack. Treatment with Keytruda is intended to increase the immune system’s anti-cancer response.

The KEYNOTE-028 trial investigated the efficacy and safety of Keytruda in 24 SCLC patients whose tumors were positive for the PD-L1 factor — which usually predicts response to Keytruda. The trial also included 19 other groups of patients with different cancer types.

Participants had received at least one prior line of therapy, while 87.5% had been treated with two or more therapies. All had received first-line platinum-based chemotherapy plus etoposide.

Keytruda (10 mg/kg) was given every two weeks for two years or until disease progression or intolerable toxicity occurred.

After a median follow-up of 9.8 months, eight patients (33.3%) experienced a reduction in their tumor burden, with one patient showing a complete response, or the total disappearance of tumor signs. One additional patient had their disease stabilized for less than six months.

Responses lasted a median of 19.4 months, and patients remained alive and without disease progression for a median of 1.9 months. Median overall survival was 9.7 months, with 37.7% of patients living past the one-year mark.

All participants experienced adverse effects, the most common of which were physical weakness, fatigue, cough, joint pain, diarrhea, insomnia, and rash. Eight patients experienced serious adverse events, including two that were determined to be treatment-related. One patient died due to an intestinal inflammation, which investigators considered “probably related” to Keytruda treatment.

The KEYNOTE-158 trial, currently recruiting participants, has already enrolled 107 SCLC patients, with a median age of 63 years, 85% of whom had one or two prior therapies.

After a median follow-up of 10.1 months, 18.7% of patients had responded to treatment, with the best responses seen in PD-L1-positive patients – 35.7% – compared with 6% among those negative for the PD-L1 factor.

Median overall survival was 9.1 months, but almost double — 14.6 months — for PD-L1 positive patients. Patients with PD-L1 negative cancers lived for a median of 7.7 months.

Treatment-related adverse effects occurred in 59% of patients, and led to four discontinuations and one death due to pneumonia.

“Keytruda has already been established as an important treatment option for many patients with advanced non-small cell lung cancer and this acceptance provides an opportunity to potentially benefit even more patients,” Cheng said.

Keytruda is also being tested as a first-line treatment for SCLC patients, given in combination with the standard platinum-based chemotherapy plus etoposide, in the KEYNOTE-604 Phase 3 trial (NCT03066778).