999P - Donafenib combined with hepatic artery infusion chemotherapy (HAIC) and sintilimab for unresectable hepatocellular carcinoma (uHCC): A prospective, single-arm phase II trial (DoHAICs study)

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.