A multicenter, phase 2 study of atezolizumab plus bevacizumab (atezo+bev) combination therapy in patients with unresectable hepatocellular carcinoma (HCC) and Child–Pugh class B cirrhosis: CHALLENGE trial final results.

587 Background: The Phase 2 CHALLENGE trial (jRCTs031210355) evaluated the safety and efficacy of atezo+bev combination therapy in patients with advanced HCC with Child–Pugh class B cirrhosis. Results of the trial’s main analysis demonstrated that atezo+bev was well-tolerated. Here, we present the trial’s final safety and efficacy outcomes. Methods: This multicenter, open-label, single-arm, Phase 2 study enrolled patients with advanced HCC and a Child–Pugh score of 7 or 8 who had not received prior systemic therapy. Patients were administered atezolizumab 1200 mg plus bevacizumab 15 mg/kg every 3 weeks. The primary endpoint was the frequency of severe adverse events (SAEs). Secondary endpoints included the objective response rate (ORR), progression-free survival (PFS), time to progression (TTP), overall survival (OS), and frequency of adverse events (AEs). Results: A total of 31 patients were enrolled between December 2021 and April 2023. Child–Pugh score was 7 points in 25 patients (80.6%) and 8 points in 6 patients (19.4%). Fourteen patients (45.2%) were classified as having Barcelona Clinic Liver Cancer stage C. We set 30 eligible patients as the population for analysis. The final analysis performed with a median follow-up duration of 517days showed that the frequency of SAEs was 30.0% (95% confidence interval [CI] 14.7–49.4%). ORRs according to RECIST 1.1 and modified RECIST were 40.0% and 46.7%, respectively. Median PFS, TTP, and OS were 240 days (95% CI: 176–526 days), 240 days (95% CI: 176–526 days), and 470 days (95% CI: 256–576 days), respectively. Frequent Grade ≥3 SAEs were blood bilirubin increased (n=3), proteinuria (n=3), hypoalbuminemia (n=2), and hypertension (n=2). Grade ≥3 severe liver-related AEs occurred in 7 patients (23.3%), including blood bilirubin increased (n=3) and esophageal varices hemorrhage (n=2). Grade ≥3 severe immune-related AEs occurred in 2 patients – these were mucositis oral (n=1) and malaise (n=1). The mean Child–Pugh score (±standard deviation) at the start of treatment was 7.2±0.4, and was 7.0±1.0, 7.2±0.9, and 7.6±1.7 at the third and fifth cycles and at the withdrawal study, respectively. Conclusions: Atezo+bev was well-tolerated with demonstrable anti-tumor effects in patients with unresectable HCC and Child–Pugh class B cirrhosis. Additional studies are warranted to confirm the efficacy results of atezo+bev in this patient group. Clinical trial information: jRCTs031210355.