A phase Ib study of anlotinib plus TQB2450 as a second-line investigational therapy in advanced hepatocellular carcinoma (aHCC).

e16184 Background: The combination of immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitor (TKI) manifested high efficacy in front-line therapy for aHCC, which still deserves further exploration in second-line therapy. Anlotinib, an oral multi-targeted TKI that mainly blocks VEGF/VEGFR pathway, has been approved for several solid tumor types in china. Anlotinib plus TQB2450, a novel anti-PD-L1 mAb, might be a promising strategy. This study aimed to evaluate the efficacy and safety of this regimen as second-line treatment in aHCC patients (pts). Methods: Pts with aHCC, ≥18 years, Child Pugh class A-B (scores ≤ 8), ECOG PS of 0-1, BCLC stage B or C, ≥ 1 measurable lesion (per RECIST v1.1) and progressed/tolerated after first-line treatment were eligible. Pts received anlotinib (10-12 mg, p.o., qd, d1-14, q3w) plus TQB2450 (1200mg, iv, d1, q3w). In the dose-escalation stage, anlotinib dose was explored from 10mg to 12mg. Dose expansion was performed after the determination of the maximum tolerable dose. Tumor assessment was evaluated according to the RECIST 1.1 per investigators, supplemented by iRECIST. The primary endpoints were ORR and safety. Secondary endpoints included PFS, DCR and OS. Results: 19 pts were enrolled between 16 May 2019 and 16 Jan 2020. The median age of pts was 52 years (range: 37-67), 89.5% pts were male, 94.7% pts were ECOG 0 and 78.9% had BCLC staging C. Both 10mg and 12mg were tolerable during the dose-escalation stage. At the cut off date (Jan 29, 2022), the median follow-up duration was 9.13 months. Of the 19 evaluable patients, 4 had PR, 8 had SD, 5 had PD, and 2 pts were NE. Confirmed ORR was 23.5% (95%CI: 6.8-49.9), DCR was 76.5% (95%CI: 50.1-93.2). The median PFS was 5.49 (3.46-7.51) months, and median DOR of 12.95 (5.26-20.63) months was achieved. Treatment-related adverse events (TRAEs) of any grade were recorded in 73.7% pts, ≥ grade 3 TRAEs were observed in 7 patients, with gastrointestinal reaction (15.8%), leucopenia (5.3%), neutropenia (5.3%), thrombocytopenia (5.3%), ALT increased (5.3%). Conclusions: Anlotinib plus TQB2450 was tolerable and showed preliminary antitumor activity in pre-treated aHCC. Further investigation in larger population is warranted. Clinical trial information: NCT03825705.