Hepatocellular CarcinomaPhase 2NCT07157306
Gecacitinib Combined With Donafenib and PD-1 Inhibitor as Immune Rechallenge Therapy for Unresectable Hepatocellular Carcinoma
A Phase 2 study testing Gecacitinib Combined With Donafenib and PD-1 Inhibitor in people with Hepatocellular Carcinoma, run by Tianjin Medical University Cancer Institute and Hospital at 1 site in China.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Gecacitinib Combined With Donafenib and PD-1 Inhibitor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteChina
- Study dates
- 10 Sep 2025to 1 Jan 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 9.ECOG PS 0-1. 10.Child-Pugh ≤7.
Who cannot join
- 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.
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Tianjin Medical University Cancer Institute and Hospital
Tianjin, Tianjin Municipality, 300060
About this study
Official title: Gecacitinib Combined With Donafenib and PD-1 Inhibitor as Second-Line Therapy for Unresectable Hepatocellular Carcinoma Failed in Immunotherapy, A Phase II Prospective Clinical Study
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
Read the 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.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Gecacitinib Combined With Donafenib and PD-1 Inhibitor
- Keywords
- Immune re-challenge for HCC
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gecacitinib Combined With Donafenib and PD-1 InhibitorDrug
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 group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Gecacitinib Combined With Donafenib and PD-1 Inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
ORR
Evaluation of tumor burden based on mRECIST criteria
Measured: 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
Measured: From date of enrollment until the date of death from any cause, assessed up to 3 years
PFS
Evaluation of tumor burden based on mRECIST criteria
Measured: 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
Evaluation of tumor burden based on mRECIST criteria
Measured: 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)
Number of patients with AE, treatment-related AE (TRAE), serious adverse event (SAE) assessed by CTCAE v5.0
Measured: From date of enrollment until the date of 30 days after the last treatment according to the protocol, assessed up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2025
- Study start10 Sep 2025 (estimated)
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Tianjin Medical University Cancer Institute and HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wei Zhang, Tianjin Medical University Cancer Institute and Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07157306
- Sponsor's protocol ID
- E20250854
- Status last verified
- Aug 2025
- First submitted
- 14 Aug 2025
- Last updated
- 5 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38900877Zak 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.
PubMed 38900864
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gecacitinib Combined With Donafenib and PD-1 Inhibitor as Second-Line Therapy for Unresectable Hepatocellular Carcinoma Failed in Immunotherapy, A Phase II Prospective Clinical Study
- ClinicalTrials.gov ID
- NCT07157306
- Acronym / sponsor ID
- E20250854
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Immune re-challenge for HCC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Tianjin Medical University Cancer Institute and HospitalUniversity, hospital or other
- Study start
- 10 Sep 2025 (estimated)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Jan 2028 (estimated)
- First posted
- 5 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| study arm | Experimental | Drug: Gecacitinib Combined With Donafenib and PD-1 InhibitorThe participants in this arm will be treated with combination therapy of Gecacitinib（100mg,Bid,po）, Donafenib (200mg,Bid,po), and PD-1(Q3W,iv). |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (9 listed)
- Fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma confirmed by histology or cytology.
- History of malignant tumor, excluding the following cases:
- Diffuse tumor lesion.
- Preexisting or history of hepatic encephalopathy, hepatorenal syndrome or liver transplantation.
- Clinically uncontrolled ascites or pleural effusion.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gecacitinib Combined With Donafenib and PD-1 InhibitorSubjects 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. | Drug | study arm |
Primary outcome
ORR
Time frame: 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
4 secondary outcomes
OS
Time frame: From date of enrollment until the date of death from any cause, assessed up to 3 years
PFS
Time frame: 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
Time frame: 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)
Time frame: From date of enrollment until the date of 30 days after the last treatment according to the protocol, assessed up to 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2025.
- Background: PubMed 38900877Mathew 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.
- Background: PubMed 38900864Zak 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Gecacitinib Combined With Donafenib and PD-1 Inhibitor in people with Hepatocellular Carcinoma, run by Tianjin Medical University Cancer Institute and Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 5 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wei Zhang (86-2223340123 Ext. 3090, zhang.wei@tmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ORR (time frame: 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07157306, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2025.