Abstract 999P
Background
Both donafenib and anti-PD-1 antibodies are indicated for uHCC, HAIC significantly improved treatment response over TACE in patients (pts) with large uHCC in a phase III trial. Considering the different mechanisms, this study aimed to investigate the safety and efficacy of donafenib combined with HAIC and sintilimab in pts with uHCC.
Methods
This is a prospective, single-arm phase II study. Pts with histologically diagnosed uHCC, no previous systemic treatment, Child-Pugh A5-B7, ECOG performance status (PS) of 0 or 1 were eligible for inclusion. Enrolled pts received donafenib (200 mg, bid), sintilimab (200 mg, q3w) and HAIC (oxaliplatin 85 mg/m2 2h, leucovorin 400 mg/m2 2h, fluorouracil bolus 400 mg/m2 in the first 10 minutes, and fluorouracil infusion 1200 mg/m2 for 23 hours, q3w) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR).
Results
From Dec 2021 to Apr 2023, 30 pts were enrolled: BCLC stage A/B/C: 4/10/16; Child-Pugh class A/B: 29/1; ECOG PS 0/1: 29/1. The median tumor size was 7.9 cm, 46.7% pts presented macro vascular invasion, 10.0% had extrahepatic metastasis. As of May 6, 2023, the median follow-up time was 102 days, the median number of HAIC was 3 times (range, 1-8). Based on mRECIST, the ORR was 82.1% (95% CI, 63.1% - 93.9%) with 4 (14.3%) complete responses (CR) and 19 (67.8%) partial responses (PR). The disease control rate (DCR) was 96.4% (95% CI, 81.7% - 99.9%). Of 28 pts evaluable for response, the conversion success rate was 64.3% (18/28), 13 of them received hepatectomy, 5 cases (38.5%) achieved complete pathological response and 6 cases (46.2%) achieved major pathological response. The median time to response (TTR) was 2.1 months. The median progression-free survival (PFS) was 10.2 months (95% CI, NR). The most common treatment-emergent adverse events (TEAEs) were thrombocytopenia, anemia and neutropenia. Grade 3-4 TEAEs occurred in 33.3% of pts. No grade 5 TEAEs were observed.
Conclusions
Combination treatment with donafenib and HAIC plus sintilimab showed promising clinical benefits and acceptable toxic effects in pts with uHCC. The enrollment and follow-up are continuing.
Clinical trial identification
NCT05166772.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
956P - Phase II study of adjuvant tislelizumab combined with interferon-α and active surveillance in hepatocellular carcinoma patients with microvascular invasion
Presenter: Yixiu Wang
Session: Poster session 18
957P - Interim report of Notable-HCC: A phase Ib study of neoadjuvant PD-1 with stereotactic body radiotherapy in patients with resectable hepatocellular carcinoma (HCC)
Presenter: Mingming Li
Session: Poster session 18
959P - Combination therapy of envafolimab and suvemcitug in patients with hepatocellular carcinoma (HCC): Results from a phase II clinical trial
Presenter: Lixia Ma
Session: Poster session 18
960P - Personalized circulating tumor DNA (ctDNA) monitoring for recurrence detection and treatment response assessment in hepatocellular carcinoma (HCC)
Presenter: Maen Abdelrahim
Session: Poster session 18
961P - Blood circulating Galectin-3 is a prognostic biomarker in hepatocellular carcinoma
Presenter: Shadi Chamseddine
Session: Poster session 18
962P - SBRT improves the efficacy of immuno-checkpoint inhibitors for hepatocellular carcinoma through the activation of IL-6/JAK1-STAT3/PD-L1 axis mediated by MBD3 degradation
Presenter: Weiwei Yan
Session: Poster session 18
963P - Discovery and validation of cfDNA methylation, AFP and ctDNA mutation for the early detection of hepatocellular carcinoma: A multicenter prospective study (ASCEND-Hep)
Presenter: Mingxin Pan
Session: Poster session 18
966P - Potential role of neuropilin-1 in the prognosis, development and risk of invasion in hepatocellular carcinoma patients
Presenter: Tania Payo-Serafín
Session: Poster session 18