LBA40 - Primary results from the phase III ALTN-AK105-III-02 study: Anlotinib plus penpulimab versus sorafenib as first-line (1L) therapy for advanced hepatocellular carcinoma (aHCC)

Background

This randomized, controlled, openlabel, multicenter, phase III study aimed to evaluate the efficacy and safety of anlotinib (VEGFR/PDGFR/FGFR/c-kit-TKI) + penpulimab (anti-PD-1 IgG1 monoclonal antibody) vs sorafenib as 1L therapy for aHCC.

Methods

Eligible pts with aHCC were randomized 2:1 to anlotinib (10 mg, po, qd, d1-14) plus penpulimab (200 mg, iv, q3w) or sorafenib (400 mg, po, bid). Pts were stratified by macrovascular invasion and/or extrahepatic metastases, baseline serum AFP (<400 vs ≥400 ng/mL), and ECOG PS (0 vs 1). The dual primary endpoints were PFS (per RECIST v1.1 by IRC) and OS; secondary endpoints included PFS, ORR, DCR, DOR and safety. The final analysis for PFS was done after 312 PFS events occurred and the planned interim analysis of OS was done after 332 deaths occurred.

Results

649 pts were randomized (anlotinib + penpulimab, 433; sorafenib, 216). Demographic and baseline characteristics were generally balanced across arms. Overall, 41% of pts had macrovascular invasion, and 62% had extrahepatic metastasis. At the final analysis for PFS (data cutoff: 5 June 2023), 313 PFS events had occurred. The median PFS was significantly improved with anlotinib + penpulimab vs sorafenib (6.9 mo [95% CI 5.8-8.0] vs 2.8 mo [2.7-4.1]; HR 0.53 [95% CI 0.41-0.68]); p<0.0001). At interim analysis for OS (data cutoff: 29 January 2024), 338 OS events had occurred. The median OS was significantly prolonged with anlotinib + penpulimab vs sorafenib (16.5 mo [95% CI 14.7-19.7] vs 13.2 mo [95% CI 9.7-16.9]; HR 0.69 [95% CI 0.52-0.92]; p=0.0013). Incidence rates of grade ≥3 TRAEs were 48.2% in the anlotinib+penpulimab arm and 47.4% in the sorafenib arm. AEs leading to dose modification (16.2% vs 29.9%) were lower with anlotinib + penpulimab compared with sorafenib. The incidence of any grade immune-mediated AEs was lower in anlotinib+penpulimab-treated pts: pneumonitis (2.5%), colitis (0.9%), and hepatitis (0.5%).

Conclusions

The combination of anlotinib + penpulimab significantly prolonged PFS and OS vs sorafenib with no new safety signals observed, and presents as a new 1L treatment option for aHCC.

Clinical trial identification

NCT04344158.

Editorial acknowledgement

Legal entity responsible for the study

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Funding

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.