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

NCT07157306 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: E20250854
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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

Conditions

Hepatocellular Carcinoma

Keywords

Immune re-challenge for HCC

Outcome Measures

Primary Outcomes (1)

• ORR

  Evaluation of tumor burden based on mRECIST criteria

  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

Secondary Outcomes (4)

• 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

• 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

• 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

Study Arms (1)

study arm

EXPERIMENTAL

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).

Drug: Gecacitinib Combined With Donafenib and PD-1 Inhibitor

Interventions

Gecacitinib Combined With Donafenib and PD-1 Inhibitor DRUG

Subjects were enrolled and started receiving treatment with Gecacitinib (100mg, Bid, po) for 7 consecutive days; thereafter, they were treated with PD-1 antibody (Q3W, iv) and Donafenib (200mg, Bid, po), counting the day of infusion of PD-1 monoclonal antibodies as C1D1, with each cycle lasting 3 weeks. Subsequent treatments involved administering Gecacitinib for 1 week before each infusion of PD-1.

study arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age and gender: \>18 years old and≤75 years old, both men and women.
• All subjects must have Hepatocellular Carcinoma confirmed by pathological or clinical diagnosis.
• Patients with viable and measurable target lesion per RECIST 1.1.
• Patients with unresectable hepatocellular carcinoma (uHCC) who experienced disease progression after first-line therapy containing immune checkpoint inhibitors.
• Patients who are expected to live more than 3 months.
• ECOG PS 0-1. 10.Child-Pugh ≤7.

You may not qualify if:

• Fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma confirmed by histology or cytology.
• History of malignant tumor, excluding the following cases:
• Malignant tumor that was curatively treated more than 5 years prior to study entry and has not recurred since then;
• 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.
• Diffuse tumor lesion.
• Preexisting or history of hepatic encephalopathy, hepatorenal syndrome or liver transplantation.
• Clinically uncontrolled ascites or pleural effusion.
• Received treatment with a JAK inhibitor previously .
• 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.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, 300060, China

Location

Related Publications (2)

• Mathew D, Marmarelis ME, Foley C, Bauml JM, Ye D, Ghinnagow R, Ngiow SF, Klapholz M, Jun S, Zhang Z, Zorc R, Davis CW, Diehn M, Giles JR, Huang AC, Hwang WT, Zhang NR, Schoenfeld AJ, Carpenter EL, Langer CJ, Wherry EJ, Minn AJ. Combined JAK inhibition and PD-1 immunotherapy for non-small cell lung cancer patients. Science. 2024 Jun 21;384(6702):eadf1329. doi: 10.1126/science.adf1329. Epub 2024 Jun 21.

  PMID: 38900877 BACKGROUND

• Zak J, Pratumchai I, Marro BS, Marquardt KL, Zavareh RB, Lairson LL, Oldstone MBA, Varner JA, Hegerova L, Cao Q, Farooq U, Kenkre VP, Bachanova V, Teijaro JR. JAK inhibition enhances checkpoint blockade immunotherapy in patients with Hodgkin lymphoma. Science. 2024 Jun 21;384(6702):eade8520. doi: 10.1126/science.ade8520. Epub 2024 Jun 21.

  PMID: 38900864 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

donafenib; Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Wei Zhang

CONTACT

86-2223340123 Ext. 3090; zhang.wei@tmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 14, 2025
• First Posted: September 5, 2025
• Study Start: September 10, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: September 5, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)