NCT06354387

Alectinib in Combination With Nivolumab in the Treatment of Recurrent or Refractory HCC Patients Guided With Serum RNase1 and Tumor Expression of PD-L1

A Pilot Study of Alectinib (Alecensa) in Combination With Nivolumab (Opdivo) in the Treatment of Recurrent or Refractory Hepatocellular Carcinoma Patients Guided With Serum Level of RNase1 and Tumor Expression of PD-L1

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: China Medical University Hospital · Academic / Other
• Sex: All
• Age: 20 Years
• Healthy volunteers: Not accepted

Summary

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death and the second most deadly malignancy in Taiwan. Despite decades' intensive studies, surgery and local-regional chemo-embolization, radio-frequency ablation or radiation therapy remain the mainstay of HCC treatments.

Detailed description

For HCC that are not resectable and not amenable to loco-regional therapies, the tyrosine kinase inhibitors (TKIs) sorafenib and its derivative regorafenib, lenvatinib and caboxantinib are of the standard systemic therapy. However, on average only marginal improvement of overall survival has been achieved with significant variation in response to TKI among patients. Effective predictive biomarkers to stratify patients for effective treatments have yet to be discovered. In recent researches, the investigators have found RNase1 was highly expressed in nivolumab non-response HCC patients, and human ribonuclease1 (RNase1) secreted by tumor cells, was positive correlated with PD-L1 level in HCC patients. Notably, the investigators also found RNase1 regulates macrophage polarization and promotes immunosuppression in immunotherapy by activating ALK signaling in macrophage. the investigators showed that RNase1-overexpressing tumors were sensitive to ALK inhibitor and anti-PD-1 combinational therapy in HCC orthotopic mouse model. Thus the investigators hypothesize that RNase1 is a potential biomarker for ALK inhibitor and anti-PD-1 combinational therapy in HCC. HCC patients who fit into the criteria would be benefit from ALK inhibitor (alectinib) and anti-PD-1 agent (nivolumab) combinational therapy. To test the role of circulatory RNase1 as a predictive biomarker for responsiveness to ALK inhibitor (alectinib) and anti-PD-1 agent (nivolumab) combinational therapy in Recurrent or Refractory HCC patients, the investigators propose the following pilot clinical studies in patients of HCC who failed the standard TKIs treatment. Total 8 evaluable subjects will be included. Participants will receive Alectinib (Alecensa) which has been approved for the treatment of ALK(+) NSCLC,ROS-1(+) NSCLC; and Nivolumab (Opdivo) has been approved for the treatment of several cancer types. Both of Alectinib and Nivolumab have also been under the reimbursement policy of Taiwan NHIA.

Conditions

• Hepatocellular Carcinoma

Interventions

Type	Name	Description
DRUG	Alectinib (Alecensa), Nivolumab (Opdivo)	Alectinib (Alecensa) in Combination with Nivolumab (Opdivo)

Timeline

• Start date: 2022-02-16
• Primary completion: 2026-02-28
• Completion: 2026-02-28
• First posted: 2024-04-09
• Last updated: 2026-03-19

Locations

1 site across 1 country: Taiwan