Gecacitinib Combined With Donafenib and PD-1 Inhibitor as Immune Rechallenge Therapy for Unresectable Hepatocellular Carcinoma

Not Applicable

Not yet recruiting

• Conditions: Hepatocellular Carcinoma
• Interventions: Drug: Gecacitinib Combined With Donafenib and PD-1 Inhibitor

• Registration Number: NCT07157306
• Lead Sponsor: Tianjin Medical University Cancer Institute and Hospital

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of Gecacitinib Combined With Donafenib and PD-1 Inhibitor as Immune Rechallenge Therapy for Unresectable Hepatocellular Carcinoma

Detailed Description

Jak inhibitors have already demonstrated the ability to reverse T-cell exhaustion in the treatment of Hodgkin lymphoma. Gecacitinib is a Jak inhibitor that has been approved for the treatment of bone marrow fibrosis. This study was designed to evaluate the safety and efficacy of Gecacitinib Combined With Donafenib and PD-1 Inhibitor as Immune Rechallenge Therapy for Unresectable Hepatocellular Carcinoma . Total 35 subjects will be recruited in this study, ORR will be will be used as primary outcome measures, OS, PFS, DCR and safety will be the secondary endpoints.

Study Timeline

• Status Verified: 2025-08
• Study First Submitted: 2025-08-14
• Study First Submitted QC: 2025-08-28
• Last Update Submitted: 2025-08-28
• Study First Posted: 2025-09-05
• Last Update Posted: 2025-09-05
• Study Start: 2025-09-10
• Primary Completion: 2027-01-01
• Study Completion: 2028-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

1. Age and gender: >18 years old and≤75 years old, both men and women.
2. All subjects must have Hepatocellular Carcinoma confirmed by pathological or clinical diagnosis.
3. Patients with viable and measurable target lesion per RECIST 1.1.
4. Patients with unresectable hepatocellular carcinoma (uHCC) who experienced disease progression after first-line therapy containing immune checkpoint inhibitors.
5. Patients who are expected to live more than 3 months.

9.ECOG PS 0-1. 10.Child-Pugh ≤7.

Exclusion Criteria

1. Fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma confirmed by histology or cytology.

2. History of malignant tumor, excluding the following cases:

   1. Malignant tumor that was curatively treated more than 5 years prior to study entry and has not recurred since then;
   2. Successful radical resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder carcinoma, preinvasive cervix carcinoma, and other preinvasive cancers.

3. Diffuse tumor lesion.

4. Preexisting or history of hepatic encephalopathy, hepatorenal syndrome or liver transplantation.

5. Clinically uncontrolled ascites or pleural effusion.

6. Received treatment with a JAK inhibitor previously .

7. Clinically severe gastrointestinal bleeding within 6 months of the start of treatment or any life-threatening bleeding events within 3 months of the start of treatment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
study arm	Gecacitinib Combined With Donafenib and PD-1 Inhibitor	The participants in this arm will be treated with combination therapy of Gecacitinib（100mg,Bid,po）, Donafenib (200mg,Bid,po), and PD-1(Q3W,iv).

Primary Outcome Measures

Name	Time	Method
ORR	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years	Evaluation of tumor burden based on mRECIST criteria

Secondary Outcome Measures

Name	Time	Method
DCR	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years	Evaluation of tumor burden based on mRECIST criteria
OS	From date of enrollment until the date of death from any cause, assessed up to 3 years
PFS	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years	Evaluation of tumor burden based on mRECIST criteria
Incidence of treatment-related adverse events (TRAE)	From date of enrollment until the date of 30 days after the last treatment according to the protocol, assessed up to 3 years	Number of patients with AE, treatment-related AE (TRAE), serious adverse event (SAE) assessed by CTCAE v5.0

Trial Locations

Locations (1)

Tianjin Medical University Cancer Institute and Hospital; 🇨🇳 Tianjin, Tianjin Municipality, China