Pembrolizumab Approved in China for Melanoma

Roy Baynes, MD, PhD

The China National Drug Administration has approved pembrolizumab (Keytruda) for the treatment of adult patients with unresectable or metastatic melanoma after 1 prior line of therapy, according to Merck (MSD) the manufacturer of the PD-1 inhibitor.

The approval was based on overall response rate (ORR) results from the phase Ib KEYNOTE-151 study, in which single-agent pembrolizumab was examined in a population of 103 Chinese patients with locally advanced or metastatic melanoma following 1 prior line of systemic therapy. No specific data are available, with Merck intending to present the results at an upcoming medical meeting.

“Merck is committed to bringing new treatment advances, like Keytruda, to cancer patients in China,” Roy Baynes, MD, PhD, senior vice president and head of Global Clinical Development, chief medical officer, Merck Research Laboratories, said in a statement.

“The approval of Keytruda in China, for this first indication, was made possible through extensive collaborative effort with the Chinese patients and investigators who participated in KEYNOTE-151, as well as the regulatory and government authorities who prioritized this filing. We appreciate their commitment to bringing forward the first ant—PD-1 therapy for advanced melanoma in China,” added Baynes.

In the multicenter, single-arm, open-label phase Ib KEYNOTE-151 trial, patients were treated with pembrolizumab monotherapy at 2 mg/kg every 3 weeks. Beyond the primary endpoint of ORR, secondary outcome measures included duration of response, progression-free survival, and overall survival (OS).

“Over the past decades, we have had limited effective options in the treatment of patients with advanced melanoma,” KEYNOTE-151 primary investigator Jun Guo, MD, PhD, director of the Department of Melanoma & Renal Cancer, Peking University Cancer Hospital and Institute Secretary-General of the Chinese Society of Clinical Oncology, said in a statement.

“Advanced melanoma is one of the cancers that has been most responsive to immunotherapy, and outside of China, anti—PD-1 therapies such as pembrolizumab have become the standard therapy for this disease. With the approval of pembrolizumab in China, the treatment of advanced melanoma will now be aligned with international standards,” added Guo.

In the United States, single-agent pembrolizumab is approved by the FDA for the treatment of patients with unresectable or metastatic melanoma. Several trials supported the PD-1 inhibitor’s authorized usage, including the KEYNOTE-006 trial, which randomized 834 patients with unresectable stage III or stage IV advanced melanoma to 4 cycles of ipilimumab (Yervoy) at 3 mg/kg every 3 weeks (n = 278); 10 mg/kg of pembrolizumab every 3 weeks (n = 277); or 10 mg/kg of pembrolizumab every 2 weeks (n = 279).

Patients enrolled on the multicenter, open-label, randomized study previously received either 0 or 1 prior lines of therapy, excluding immunotherapy with CTLA-4, PD-1, or PD-L1 inhibitors. Of the overall patient population, 65.8% did not receive prior systemic treatment for their advanced melanoma. About 80% of the patients involved had positive PD-L1 staining, 18% had negative staining, and 2% of the population was unknown. Patients also had an ECOG performance status of 0 or 1.

Results from the trial showed that OS—which was a primary endpoint—was superior in both pembrolizumab arms compared with the ipilimumab arm. The 12-month OS rate was 74% for patients who had pembrolizumab every 2 weeks, 68% for patients who had pembrolizumab every 3 weeks, and 59% for patients receiving ipilimumab.

At the 2-year mark, both pembrolizumab arms had a 55% OS rate versus 43% for those in the ipilimumab arm. The median OS at 2 years was not reached for either pembrolizumab treatment arm compared with 16 months for the ipilimumab arm (HR, 0.68; 95% CI, 0.53-0.87 for pembrolizumab every 2 weeks vs ipilimumab; P = .0009 and HR, 0.68; 0.53-0.86 for pembrolizumab every 3 weeks vs ipilimumab; P = .0008).

The ORR was 37% for patients receiving pembrolizumab every 2 weeks, 36% for the every-3-week regimen, and 13% with ipilimumab (P <.001). The complete response rates were 12%, 13%, and 5%, respectively.

Schachter J, Ribas A, Long GV, et al. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet Oncol. 2017;390(10105):1853-1862. doi: 10.1016/S0140-6736(17)31601-X.