Updated efficacy and safety results from a phase 1b study of the PD-1 antagonist CS1003 combined with lenvatinib (LEN) as first-line (1L) treatment in Chinese patients (pts) with unresectable hepatocellular carcinoma (uHCC).
Authors: Shen Lin , Guo Ye , Zhang Yanqiao , Li Wei , Gong Jifang , Li Qun , Ma Zhigang , Wang Nanya , Su Rila , Cai Zhongheng , Guo Rong , Li Peiqi , Tse Archie N. 
Published: June 2022

e16191 Background: CS1003 is a novel humanized, recombinant IgG4 anti-PD-1 monoclonal antibody. LEN, a multi-kinase inhibitor of VEGFR 1-3, FGFR 1-4, PDGFRα, RET, and KIT, is approved as 1L treatment in pts with uHCC in multiple countries. A multi-regional, double-blinded, randomized phase 3 trial (CS1003-305, NCT04194775) of CS1003/placebo in combination with LEN as 1L treatment in uHCC is underway. The preliminary efficacy and safety data from the open-label phase 1b study of CS1003 + LEN as 1L treatment in uHCC after a median 6.2 months of follow-up were previously reported at ESMO Congress 2020. Here we present the updated results with a median 18.0 months of follow-up. Methods: Pts with uHCC, BCLC stage B or C, Child-Pugh class A, and ECOG PS ≤ 1 received 200 mg CS1003 intravenously once every 3 weeks and LEN orally (body weight ≥ 60 kg: 12 mg; < 60 kg: 8 mg) daily as 1L treatment. The primary endpoint was objective response rate (ORR) assessed by investigators per RECIST v1.1. Secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety. Data cutoff for this final analysis was August 13, 2021. Results: At data cutoff, a total of 20 pts had received treatment. Compared with the last preliminary analysis, confirmed ORR was changed from 30.0% to 45.0% (95% CI: 23.06%, 68.47%) with 9 pts achieving partial response. DCR was 90.0% with 9 pts having stable disease as best overall response. DOR ranged from 4.2 to 18.7+ months, and median DOR in all responders had not been reached. Median PFS was extended compared with the previous study readout from 8.4 months to 10.4 months (95% CI: 6.2, not estimable) with 6-month and 12-month PFS rates of 85.0% and 48.2%, respectively. Median OS had not been reached. All adverse events (AEs) were grade 1-3. Grade 3 AEs attributed to CS1003 and/or LEN occurred in 9 (45.0%) pts with the most common being gamma-glutamyltransferase increased (2 pts, 10.0%). Six (6) pts experienced grade 3 CS1003-related AEs, among whom, 4 pts also experienced grade 3 AEs related to LEN. Only 2 pts discontinued treatment due to AEs. There were no deaths due to AEs, and no new safety signals were identified. Conclusions: The antitumor activity of CS1003 + LEN combination as 1L treatment in Chinese pts with uHCC remains encouraging and durable through a longer follow-up period, and the safety profile is well tolerated and manageable. The PFS is longer and the ORR is higher compared to the data previously reported, which support further development as a combination treatment for improving outcomes in uHCC pts. The ongoing multi-regional, double-blinded, randomized, placebo-controlled, phase 3 trial (CS1003-305, NCT04194775) is currently recruiting and will further evaluate adding CS1003 to LEN as a 1L treatment in uHCC. Clinical trial information: NCT03809767.