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)

Background

So far there is no neoadjuvant therapy recommended by major hepatocellular carcinoma (HCC) guidelines. In other malignancies, ICIs in the neoadjuvant setting have shown better outcomes than in the adjuvant setting, and the combination of radiation therapy to ICIs incrementally improves the systemic response to ICIs. Neoadjuvant therapy of ICIs plus stereotactic body radiotherapy (SBRT) has shown promising results in several types of solid tumours but not HCC.

Methods

This is a phase Ib clinical trial of neoadjuvant SBRT plus PD-1 (tislelizumab) in HCC patients (pts). Prior to resection, pts receive 8 Gy × 3 SBRT with 2 cycles of PD-1. HCC resection is scheduled 4 weeks after the second PD-1, followed by adjuvant PD-1 for up to 1 year. We plan to enrol 20 participants in this trial. The primary study endpoints include the surgery delay over 6 weeks or later, ORR on pre-resection imaging, pathologic response (pCR) rate, safety and tolerability of the sequential SBRT/PD-1. The secondary endpoints are DFS and OS rates every 3 or 6 months after the hepatic resection.

Results

By 10^th May 2023, 11 pts were enrolled, all were BCLC A stage. One pt was excluded due to the protocol violation, in other 10 pts, one just starts the adjuvant therapy, two have completed the neoadjuvant therapy and waiting for the scheduled resection, all other 7 pts have completed the resection, and no surgery delay accrued; DCR reached 100% (RECIST: 1 PR, 6 SD; mRECIST: 1 CR, 2 PR, 3 SD, 1 CR+SD ); pCR was confirmed in two tumors; So far the safety of neoadjuvant SBRT+PD-1 was satisfied, grade 1 to 2 TRAEs, mainly anemia and white blood cell decreasing were common; grade 3 TRAE occurred in 3 pts (1 granulocytopenia and 2 elevated transaminase), but all well-tolerated. One pt developed recurrence 9 months after surgery (RF ablation), all other 6 pts are still in DFS. Table: 957P

Conclusions

The safety and clinical significance of radiotherapy plus PD-1 as the neoadjuvant therapy in HCC needs further exploration.

Clinical trial identification

NCT05185531.

Editorial acknowledgement

N/A

Legal entity responsible for the study

The authors.

Funding

The Key Research and Development Program of Shandong (Major Science & Technology Innovation Project), 2021SFGC0501. The reported trial is partly funded by BeiGene.

Disclosure

L. Zhao: Financial Interests, Personal, Speaker’s Bureau: Innovent, Hengrui Medicine, MSD, Roche, Bayer; Financial Interests, Personal and Institutional, Speaker’s Bureau. All other authors have declared no conflicts of interest.