Noninferior OS End Point Met With First-line Tislelizumab Vs Sorafenib in Unresectable HCC

The phase 3 RATIONALE 301 trial examining first-line tislelizumab vs sorafenib in unresectable hepatocellular carcinoma met the primary end point of noninferior overall survival.

The phase 3 RATIONALE 301 trial (NCT03412773) met its primary end point of noninferior overall survival with tislelizumab (BGB-A317) for patients with unresectable hepatocellular carcinoma (HCC) receiving treatment in the frontline setting compared with sorafenib (Nexavar), according to a press release from BeiGene.

No new safety signals were reported as they remained consistent with previous studies. Tislelizumab is a humanized IgG4 anti–PD-1 monoclonal antibody that was designed to minimize binding to Fc-gamma receptors on macrophages which helps immune cells attack tumors. The data will be presented at an upcoming conference.

“Patients with unresectable HCC face a devastating prognosis, with a median life expectancy of 1 year. Currently, there are few treatment options if patients cannot tolerate [tyrosine kinase inhibitor] therapy or if their condition progresses,” Mark Lanasa MD, PhD, chief medical officer of Solid Tumors at BeiGene, said in the press release. “We are encouraged by the outcome of the final analysis of RATIONALE 301 and look forward to sharing the full safety and efficacy results at an upcoming medical conference.”

A total of 674 patients were enrolled in the randomized, open-label trial. Patients were given either tislelizumab at 200 mg intravenously once every 3 weeks or 400 mg of sorafenib orally twice daily. Safety was also assessed as a dual primary end point in Japan only. Secondary end points included objective response rate, progression-free survival, duration of response, time to progression, and health-related quality of life.

Patients were eligible for treatment if they had a confirmed diagnosis of HCC, Barcelona Clinic Liver Cancer stage B or C, and no prior systemic therapy. Additional requirements included having a Child-Pugh score A, an ECOG performance status of 1 or less, and adequate organ function.

Exclusion criteria included having known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology. Patients must not have tumor thrombus implicating the main trunk of portal vein or inferior vena cava, loco-regional therapy to the liver within 28 days before randomization, or clinical evidence of portal hypertension with bleeding esophageal or gastric varices during screening or within 6 months of randomization.


BeiGene announces positive global phase 3 trial results for PD-1 inhibitor tislelizumab in first-line unresectable hepatocellular cancer. News Release. BeiGene. August 9, 2022. Accessed August 10, 2022.