The phase 3 RATIONALE 301 trial of tislelizumab in patients with unresectable hepatocellular carcinoma has met its primary end point of non-inferior overall survival.
Tislelizumab met its primary end point of non-inferior overall survival (OS) compared with sorafenib (Nexavar) in the first-line in adult patients with unresectable hepatocellular carcinoma (HCC), according to BeiGene.1
Results come from a readout of results from the phase 3 RATIONALE 301 (NCT03412773), Findings also showed there were no new safety signals reported, and the safety profile for tislelizumab was consistent with previous studies.
These results mark the eighth positive phase 3 trial for tislelizumab across various cancer types and in multiple lines of therapy. Full results are expected to be submitted for presentation at an upcoming medical conference.
“Patients with unresectable HCC face a devastating prognosis, with a median life expectancy of one year. Currently, there are few treatment options if patients cannot tolerate TKI therapy or if their condition progresses,” said Mark Lanasa MD, PhD, chief medical officer, Solid Tumors at BeiGene, 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.”
Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages. The antibody helps aid the body’s immune cells which detect and fight against tumors. Preclinical studies have shown that binding to Fcγ receptors on macrophages have been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells.
In the randomized, open-label, multicenter, global, phase 3 RATIONALE 301 study, the safety and efficacy of tislelizumab were compared with sorafenib as a first-line treatment in adult patients with unresectable HCC.2
A total of 674 patients aged 18 years and older were enrolled in the trial. Those eligible for enrollment had a histologically confirmed diagnosis of HCC, Barcelona Clinic Liver Cancer stage B or C disease that is not amenable to or progressing after loco-regional therapy and not amenable to a curative treatment approach, received no prior systemic therapy for HCC, and measurable disease. Further eligibility criteria included Child-Pugh score A, an ECOG performance status of 0 or 1, and adequate organ function.
In the experimental arm (arm A), patients were administered intravenous tislelizumab at 200 mg once every 3 weeks. Those in the active comparator arm (arm B) were given sorafenib at 400 mg twice a day.
The primary end point of the study is non-inferiority of OS between the 2 treatment groups from the date of randomization up to 4 years key secondary end points of objective response rate, progression-free survival, durability of response, time to progression per BIRC, health-related quality of life, disease control rate, clinical benefit rate, safety, and tolerability.