Merck announced the final results from the Phase 3 KEYNOTE-394 trial investigating KEYTRUDA, Merck's anti-PD-1 therapy, plus best supportive care (BSC) in patients in Asia with advanced hepatocellular carcinoma (HCC) previously treated with sorafenib. KEYNOTE-394 is the first trial with an anti-PD-1/L1 as a second-line monotherapy treatment to show an improvement in overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) compared to placebo plus BSC for these patients. These data add to the body of evidence relating to the use of KEYTRUDA as a monotherapy in second-line HCC post sorafenib.

KEYTRUDA plus BSC demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of OS, reducing the risk of death by 21% (HR=0.79 [95% CI, 0.63-0.99]; p=0.0180) compared to placebo plus BSC for patients with previously treated advanced HCC. For patients treated with KEYTRUDA plus BSC, median OS was 14.6 months (95% CI, 12.6-18.0) compared to 13.0 months (95% CI, 10.5-15.1) for patients treated with placebo plus BSC. The percentage of patients who were alive at two years was 34.3% for KEYTRUDA plus BSC compared to 24.9% for placebo plus BSC.

These data will be presented at the 2022 American Society of Clinical Oncology Gastrointestinal Cancers (ASCO GI) Symposium (Abstract #352788) on January 21 at 10:15 a.m. ET. Treatment-related adverse events (TRAEs) occurred in 66.9% of patients in the KEYTRUDA plus BSC arm and 49.7% of patients in the placebo plus BSC arm, and Grade 3-5 TRAEs occurred in 14.4% of patients in the KEYTRUDA plus BSC arm and 5.9% of patients in placebo plus BSC arm. Immune-mediated adverse events (AEs) of any grade occurred in 18.1% of patients receiving KEYTRUDA plus BSC and 10.5% of patients receiving placebo plus BSC.

Grade 3-5 immune-mediated AEs occurred in 3.0% of patients receiving KEYTRUDA plus BSC. There were three deaths (due to gastrointestinal hemorrhage, autoimmune hepatitis, and soft tissue infection) in the KEYTRUDA arm related to the study intervention. In the U.S., KEYTRUDA is indicated for the treatment of patients with HCC who have been previously treated with sorafenib based on ORR and duration of response (DOR) data from KEYNOTE-224.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. Data from KEYNOTE-394 are being discussed with global regulatory authorities and will be evaluated as a potential confirmatory study in the U.S. Merck is dedicated to advancing research in HCC and has a global development program of seven clinical trials that have enrolled or are expected to enroll approximately 3,000 patients.

In HCC, KEYTRUDA is being studied across multiple settings and lines of therapy as monotherapy and in combination with other treatments, including therapies through collaborations. KEYNOTE-394 (ClinicalTrials.gov, NCT03062358) is a randomized, double-blind Phase 3 trial evaluating KEYTRUDA plus BSC versus placebo plus BSC in Asian patients with advanced HCC previously treated with sorafenib or oxaliplatin-based chemotherapy. The primary endpoint is OS.

Additional endpoints include PFS, ORR, and DOR. The study enrolled 453 patients who were randomized to receive either KEYTRUDA (intravenously every three weeks for up to 35 cycles of treatment [up to approximately two years]) plus BSC (including pain management and management of other potential complications including ascites per local standards of care) or placebo plus BSC. Additional efficacy endpoint results of the trial showed KEYTRUDA plus BSC reduced the risk of disease progression or death by 26% (HR=0.74 [95% CI, 0.60-0.92]; p=0.0032) compared to placebo plus BSC.

Median PFS was 2.6 months (95% CI, 1.5-2.8) for KEYTRUDA plus BSC and 2.3 months (95% CI, 1.4-2.8) for placebo plus BSC. KEYTRUDA plus BSC showed an ORR of 12.7% (95% CI, 9.1-17.0) and a median DOR of 23.9 months (range, 2.8 to 32.0+), where placebo plus BSC showed an ORR of 1.3% (95% CI, 0.2-4.6) and a median DOR of 5.6 months (range, 3.0+ to 5.6).