Successful Phase II trial of Keytruda in patients with advanced liver cancer.

The phase II KEYNOTE-224 trial investigating the use of Keytruda (pembrolizumab), Merck's anti-PD-1 therapy, in patients with advanced hepatocellular carcinoma (HCC), the most common type of liver cancer, who were previously treated with systemic therapy (sorafenib) have been announced.

Results showed an overall response rate (ORR) of 16.3 percent (95% CI, 9.8-24.9) (n=17/104) with Keytruda as monotherapy. Data also include six-month overall survival (OS) and progression-free survival (PFS) rates. The findings will be presented at the 2018 American Society of Clinical Oncology Gastrointestinal (ASCO GI) Cancers Symposium in San Francisco in an oral presentation on Friday, Jan. 19, from 1:10-1:15 p.m. PT (Location: Level 3 – Room 3014) (Abstract #209).

Data in Previously Treated Advanced HCC, KEYNOTE-224 (Abstract #209) - KEYNOTE-224 is a registrational, open-label phase II trial investigating Keytruda monotherapy in patients with advanced HCC who had previously received systemic therapy with sorafenib. The primary endpoint is ORR; secondary endpoints include duration of response, disease control rate, time to progression, PFS and OS. Findings presented at ASCO GI were based on data from 104 evaluable patients, previously treated with sorafenib, who received one or more doses of KEYTRUDA (200 mg intravenous infusion on day 1 of each 3-week cycle for up to 35 administrations). Data showed an ORR of 16.3 percent (95% CI, 9.8-24.9) (n=17/104) with a complete response rate of one percent (95% CI, 0.0-5.2) and a partial response rate of 15.4 percent (95% CI, 9.1-23.8). ORR was similar across subgroups with different etiology, including Hepatitis B and Hepatitis C positive patients. At the time of analysis, the median duration of response was 8.2 months (range: 2.3+ to 8.3+) with 94 percent of responses ongoing for six months or longer (calculated per Kaplan-Meier method). The disease control rate was 61.5 percent (95% CI, 51.5-70.9) (n=64/104). The median PFS was 4.8 months (95% CI, 3.4-6.6) with a six-month PFS rate of 43.1 percent. The median OS had not been reached at the time of analysis (95% CI, 9.4-not reached) with a six-month OS rate of 77.9 percent.

The safety profile ofKeytruda was consistent with that observed in previously reported studies. The treatment-related adverse events (any grade occurring in 10% or more of patients) were fatigue (12.5%), increased aspartate aminotransferase (9.6%), diarrhea (9.6%) and pruritus (21.2%). Grade 3-5 treatment-related adverse events occurred in 26 (25%) patients and there was one treatment-related death. Immune-mediated adverse events occurred in 2.9 percent of patients. Seven patients discontinued treatment due to treatment-related adverse events.

Comment: Opdivo showed an 18.2% overall response rate in a phase 1/II study, with 3.2% of patients responding completely to support its its liver cancer approval.