Keytruda (pembrolizumab) + Lenvima (lenvatinib) in combination with Transarterial Chemoembolization significantly improved progression-free survival compared to TACE alone in unresectable, non-metastatic hepatocellular carcinoma

After a median follow-up of 25.6 months (range, 12.6-43.5), Keytruda plus Lenvima in combination with TACE demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS), reducing the risk of disease progression or death by 34% (HR=0.66 [95% CI, 0.51-0.84]; p=0.0002) compared to TACE alone. Median PFS was 14.6 months (95% CI, 12.6-16.7) for the Keytruda plus Lenvima-based regimen versus 10.0 months (95% CI, 8.1-12.2) for TACE alone. At this analysis, a trend toward improvement in overall survival (OS), the trial’s other primary endpoint, was observed for the Keytruda plus Lenvima-based regimen versus TACE alone (HR=0.80 [95% CI, 0.57-1.11]; p=0.0867); the OS data are not mature and did not reach statistical significance at the time of this interim analysis. The trial is continuing, and follow-up of OS is ongoing.

 The safety profile of the Keytruda plus Lenvima -based regimen was consistent with that observed in previously reported studies evaluating the combination.

 Treatment was administered to 237 patients receiving the Keytruda plus Lenvima -based regimen and 241 patients receiving TACE alone. Treatment-related adverse events (TRAEs) occurred in 98.7% of patients receiving Keytruda plus Lenvima in combination with TACE versus 84.6% of patients receiving TACE alone and led to the discontinuation of both study drugs in 8.4% versus 1.2% of patients, respectively. Serious adverse events were observed in 33.3% of patients receiving Keytruda plus Lenvima in combination with TACE versus 12.4% of patients receiving TACE alone. Grade 3 or 4 TRAEs occurred in 71.3% of patients receiving Keytruda plus Levima in combination with TACE versus 31.1% for TACE alone, and TRAEs led to death in 1.7% (n=4) versus 0.4% (n=1) of patients, respectively.

Study design and additional data from LEAP-012-  LEAP-012 is a multicenter, randomized, double-blind Phase III trial (ClinicalTrials.gov, NCT04246177 ) evaluating Keytruda plus Lenvima in combination with TACE versus dual placebo plus TACE for the treatment of patients with unresectable, non-metastatic HCC. The primary endpoints are PFS as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) following a maximum of five target lesions and with a requirement that new intrahepatic lesions must meet LI-RADS 5 criteria and OS. Secondary endpoints include objective response rate, duration of response, disease control rate, and time to progression as assessed by BICR per RECIST v1.1 and Modified Response Evaluation Criteria in Solid Tumors (mRECIST), as well as PFS as assessed by BICR per mRECIST and safety.

 The study randomized 480 patients 1:1 to receive: Keytruda (400 mg intravenously [IV] every six weeks [Q6W]) plus Lenvima 12 mg [for participants with screening body weight greater than 60 kg] or 8 mg [for participants with screening body weight less than 60 kg] orally once a day) in combination with TACE (conducted as a background procedure of chemotherapeutic and embolic agents injected via hepatic artery 2-4 weeks after start of study intervention, and after the first tumor assessment scan and  greater than 1 month after the first TACE); or IV placebo administered Q6W plus oral placebo administered once a day in combination with TACE. All study drugs were continued until protocol-specified discontinuation criteria. Keytruda was administered for up to two years (approximately 18 doses). After completing two years of combination therapy,Lenvima may have been administered as a single agent until protocol-specified discontinuation criteria were met.