181P - TQB2450 (PD-L1 blockade) in combination with anlotinib as a perioperative treatment for patients with hepatocellular carcinoma at high risk of recurrence: Primary results from a prospective, single-arm, phase Ib study

Background

Hepatocellular carcinoma (HCC) is an extremely aggressive tumor, and surgical resection is the primary curative treatment. However, the high rate of early recurrence results in a poor prognosis. This study aims to evaluate the efficacy and safety of TQB2450 plus anlotinib as a perioperative regimen for the treatment of resectable HCC with a high risk of recurrence.

Methods

This single-arm, phase Ib study enrolled pts with primary resectable HCC who were at high risk of recurrence. High-risk features include tumor size >5 cm, multiple tumors (≤ 3), satellite nodules, and macrovascular invasion (MVI). Before surgery, pts received 3 cycles of TQB2450 (1200 mg, IV, d1, Q3W) plus 2 cycles of anlotinib (10 mg, PO, d1-d14, Q3W). The feasibility of resection was assessed by radiographic imaging. After 30 days of surgery, patients continued combination therapy for 24 weeks. The primary endpoints were pCR and ORR (mRECIST). Secondary endpoints were PFS, OS, and safety. CRAFITY was derived from serum CRP and AFP values at baseline by adding one point each for CRP ≥1 mg/dL and AFP ≥100 ng/mL resulting in three categories: CRAFITY-low, 0 points; CRAFITY-intermediate, 1 point; CRAFITY-high, 2 points.

Results

As of July 15, 2023, 20 pts were enrolled (median age 61y [31-68], 95% male), 80% had HBV infection. All pts had Child-Pugh class A and ECOG PS 0. 11 (55%) had single (>5 cm) and 9 (45%) had multiple tumors. While n=10 (50%), n=8 (40%), and n=2 (10%) had CRAFITY-low, intermediate and high, respectively. Of 17 evaluable pts, ORR was 29.4% (5/17), 2 PR pts had low and 3 had intermediate CRAFITY scores. 13 pts completed preoperative therapy and underwent hepatic resection, the R0 resection rate was 100% and the pCR rate was 23.1% (3/13). Among the 3 pCR pts, 1 had low and 2 had intermediate CRAFITY scores; 2 had multiple tumors and no pts had MVI. 13 pts had TRAEs and grade 3/4 TRAEs (10%) including one hypertension (grade 3) and one liver damage (grade 4).

Conclusions

Neoadjuvant therapy combining TQB2450 and anlotinib shows promising results, with a tolerable safety profile. The predictive role of the CRAFITY score for HCC prognosis is worth further exploration.

Clinical trial identification

Clinical trial information: NCT04888546.

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.