Updated results of the phase II ALTER-H003 trial: Anlotinib plus toripalimab as a first-line treatment for patients with unresectable hepatocellular carcinoma.

Abstract

e16130 Background: The combination therapy of anti-angiogenic with anti-PD-1 /L1 agents has represented superior efficacy over sorafenib in the first-line treatment for unresectable HCC (uHCC). There are unmet medical needs due to limited options. Anlotinib is a novel oral multi-targeted tyrosine kinase inhibitor for tumor angiogenesis and proliferation, and has been approved for treatment of several malignancies in China. Toripalimab is a humanized IgG4 mAb against PD-1. Now we present the updated results with more patients enrolled and longer follow-up of ALTER-H003 to evaluate the efficacy and safety of anlotinib plus toripalimab as the first-line regimen for uHCC. Methods: This was a single-arm, multicenter, phase II trial. 30 patients (pts) with uHCC, previously untreated, Child-Pugh ≤7 and ECOG PS <2 will be enrolled. Pts received anlotinib (12 mg, p.o., qd, d1-14, q3w) and toripalimab (240 mg, iv, d1, q3w) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) assessed by investigator according to mRECIST and irRECIST. Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DoR) and safety. Results: By the cutoff date of January 21, 2021, 18 pts were enrolled and durations of treatment ranged from 0.1+ to 7.4+ months, 13 pts were still on treatment. 14 pts were evaluable, confirmed ORR and DCR was 21.4% (95% CI 4.7%-50.8%) and 92.9% (95% CI 66.1%-99.8%) respectively according to mRECIST. one patient achieved a complete response (CR), and one additional patient remained on treatment with unconfirmed PR. The median duration of response (DoR) has not been reached and DoRs ranges from 2.4m to 4.9m. 14 of 18 pts (77.8%) experienced treatment-related adverse events (TRAEs), Grade 3 TRAEs occurred in 7 pts (38.9%). Immune-Related TRAEs (irTRAEs) occurred in 10 pts (55.6%), few grade 3 irTRAEs were observed. No grade 4 or higher (ir)TRAEs occurred. More detailed (ir)TRAEs information were shown in Table. Conclusions: Anlotinib in combination with toripalimab showed promising anti-tumor efficacy and manageable toxicity in the first-line treatment for uHCC patients. This study is still ongoing and more data is being updated. Most common (ir)TRAEs in enrolled pts (n=18). Clinical trial information: ChiCTR1900028295. [Table: see text]