Abstract
Lenvatinib (LEN) combined with tislelizumab (TIS) plus transcatheter arterial chemoembolization (TACE) for unresectable hepatocellular carcinoma (uHCC): A single-arm, phase II clinical trial.
Author
person
Xiang Nong
Guangxi Medical University Cancer Hospital, Nanning, China
info_outline
Xiang Nong, Yu-Mei Zhang, Jing-Chang Liang, Jin-Long Xie, Zhi-Ming Zhang
Full text
Authors
person
Xiang Nong
Guangxi Medical University Cancer Hospital, Nanning, China
info_outline
Xiang Nong, Yu-Mei Zhang, Jing-Chang Liang, Jin-Long Xie, Zhi-Ming Zhang
Organizations
Guangxi Medical University Cancer Hospital, Nanning, China, Guangxi Medical University Cancer Hospital, Nnanning, China
Abstract Disclosures
Research Funding
Pharmaceutical/Biotech Company
BeiGene biopharma incorporation
Background:
uHCC still lacks effective treatments, combination of antiangiogenic targeted drugs and immune checkpoint inhibitors showed promising efficacy. TACE induces tumor necrosis and tumor antigen release, may synergize with immunotherapy. This study was to evaluate the efficacy and safety of TACE in combination with TIS and LEN in patients with uHCC.
Methods:
This study was a single-center, single-arm, open-label phase II exploratory clinical study (NCT05131698). Eligible patients were BCLC C stage and not candidates for surgical resection or liver transplantation, at least one target lesion evaluable, ECOG performance status of ≤ 1, and Child-pugh grade A or B. Enrolled patients received TACE treatment (loplatin + raltitrexed + iodine oil) followed by TIS (200 mg, IV, on Day 1 of a 21-day cycle) and LEN (body weight ≥ 60 kg: 12 mg/day; < 60 kg: 8 mg/day) daily. The primary endpoint was overall response rate (ORR) by mRECIST. The secondary endpoints included disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) and safety.
Results:
As of December 28, 2022, 31 enrolled patients with uHCC were treated. Median follow-up time is 11.3 months. Among all patients with BCLC C, 28 patients (90.3%) had microvascular invasion and 17 (54.8%) had portal vein tumor thrombus. As assessed by mRECIST, the ORR and DCR were 71.1% and 87.1%, respectively (2 CR, 6.6%; 20 PR, 64.5%; 5 SD, 16.1%), 4 patients developed tumor progression (12.9%). As assessed by RECIST 1.1, the ORR and DCR were 67.7% and 87.1%, respectively (1 CR, 3.2%; 20 PR, 64.5%; 6 SD, 19.4%), 4 patients developed tumor progression (12.9%). The median PFS was 10.2 months(95% CI: 4.5-NA), and the median OS was not reached. Any grade treatment-emergent adverse events (TEAEs) occurred in 64.5% (20/31) patients. The most common TEAEs were Increased γ-glutamyl transpeptidase (35%), Increased aspartate aminotransferase (32%), thrombopenia (25%). Only 2 patients experienced grade 3 TEAE (pneumonia). No serious adverse events (SAEs) were reported.
Conclusions:
In this study, TACE combined with TIS and LEN showed preliminary antitumor efficacy and tolerable safety profile in uHCC. Clinical trial information: NCT05131698.
Variable
All patients (n=31)
mRECIST
RECIST 1.1
Confirmed objective response, n (% [95% CI])
22 (71.1% [52.0- 85.8])
21 (67.7% [48.6- 83.3])
Complete response, n(%)
2 (6.6%)
1 (3.2%)
Partial response, n(%)
20 (64.5%)
20 (64.5%)
Stable disease, n(%)
5 (16.1%)
6 (19.4%)
Disease control, n (%[95% CI])
26 (87.1% [70.2- 96.4])
26 (87.1% [70.2- 96.4])
Progressive disease, n(%)
4 (12.9%)
4 (12.9%)
Clinical status
Clinical
4 organizations
3 drugs
3 targets
Organization
Guangxi Medical University Cancer HospitalOrganization
Nanning, ChinaOrganization
China National Biotec GroupOrganization
NnanningDrug
TACE-HAICDrug
TisagenlecleucelDrug
lenvatinibTarget
Tissue Factor (TF)Target
TACE-HAICTarget
LENTINAN