Advanced Hepatocellular CarcinomaPhase 1JAKaLNCT04358185
Itacitinib in Advanced Hepatocellular Carcinoma
A Phase 1 study testing Itacitinib in people with Advanced Hepatocellular Carcinoma, run by Imperial College London at 1 site in United Kingdom.
Trial summary
This research will assess the effects of Itacitinib as a second line treatment for patients with advanced inflammatory hepatocellular carcinoma (HCC), a type of liver cancer. Itacinib is a protein inhibitor of the tyrosine kinase, JAK1, which is believed to enable cancer cells to metastasise to other parts of the body. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Hepatocellular Carcinoma
- What is being tested?
- Itacitinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 3 Dec 2018to 7 Apr 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18 or over
- Diagnosis of hepatocellular carcinoma. If primary diagnosis of HCC: diagnosis based on the following criteria:
- cyto-histological criteria, OR
- radiological criteria: Focal lesion >1 cm with arterial hypervascularization in 2 coincident imaging techniques (CT, MRI, or US), OR
- combined criteria: one imaging technique showing a focal lesion 1-2 cm with arterial hypervascularization AND AFP levels >400 ng/mL, OR
- combined criteria: one imaging technique showing a focal lesion >2 cm with arterial hypervascularization AND AFP levels >200 ng/mL
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- Child-Pugh A and B up to 7 points (in patients receiving anticoagulant therapy; Child-Pugh score up to 5 points; INR category not regarded for calculation of the Child-Pugh score)
- Progression or intolerance to first line therapy - N.B: Date of patients last dose of therapy must be more than 28 days before enrolment into this study.
- ECOG Performance status 0, 1 or 2.
- Adequate organ function as defined by:
- Adequate hematologic function (ANC 1.0x109/l, platelet count 50x109/l, and hemoglobin 9g/dl).
- Serum creatinine concentration < 1.5 times the upper limit of normal (ULN) and/or creatinine clearance >60 ml/min
- Bilirubin level < 1.5 X ULN
- PT-INR/PTT<1.5 x ULN
- For women of child-bearing potential (defined as women who have not undergone surgical sterilization with a hysterectomy, and/or bilateral oophorectomy, and are not postmenopausal, defined as ≥12 months of amenorrhea) must have a negative serum pregnancy test within 14 days prior to the first study drug administration Effective contraception must be used throughout the duration of the study and up to 30 days following the last dose of the investigational medicinal product (IMP). Effective forms of contraception include complete abstinence from sexual intercourse, double barrier methods (condom with spermicide in conjunction with use of an intrauterine device or condom with spermicide in conjunction with use of a diaphragm), birth control patch or vaginal ring, oral, injectable, or implanted contraceptives and surgical sterilization (tubal ligation or vasectomy). Sperm and ova donation are prohibited during the duration of the study and 30days after the last dose. 8. Written informed consent prior to initiation of any study procedures and willing and able to comply with the study schedule
Who cannot join
- Previous treatment with:
- Study medication, any other JAK1 inhibitor and/or known hypersensitivity to the study medication
- An investigational agent within 28 days prior to start of study treatment
- Serious concurrent medical or psychiatric illness, including serious active infection
- Uncontrolled ascites
- Uncontrolled hypertension
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- History of organ transplant (including prior liver transplant)
- Diagnosis of HIV, congenital immune defect, any immunosuppressive therapy for autoimmune disease or inflammatory bowel disease
- Patients with active or latent tuberculosis
- Patients with active hepatitis C or active hepatitis B that requires treatment
- Patients who have received a live vaccine 30 days or fewer prior to enrolment as well as patients who intend to receive live vaccination during study participation or for three months after last dose administration
- 8. Patients who have a history of unprovoked venous thromboembolism (VTE) prior to the diagnosis of malignancy 9. Pregnant or breast feeding women Other clinically significant co-morbidities that could compromise the subject's participating in the study
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Imperial College Healthcare NHS Trust
London, W12 0HS
About this study
Official title: A Phase Ib Study of Itacitinib, a JAK1 Inhibitor, in Advanced Hepatocellular Carcinoma
This research will assess the effects of Itacitinib as a second line treatment for patients with advanced inflammatory hepatocellular carcinoma (HCC), a type of liver cancer. Itacinib is a protein inhibitor of the tyrosine kinase, JAK1, which is believed to enable cancer cells to metastasise to other parts of the body.
Read the detailed description
JAKaL is a single arm phase Ib study evaluating the effect of Itacitinib in 25 patients with advanced HCC.
Many patients diagnosed with HCC will have advanced disease where only palliative care is offered to them, this could account for the relatively low reported 5-year survival rate of approximately 10%. There are a number of epidemiological and pre-clinical studies that have investigated the role of chronic inflammatory conditions in the development of HCC and these provide evidence that inflammation promotes malignant transformation. The production of tumour-promoting cytokines by inflammatory cells can activate transcription factors, such as STAT3 via the JAK/STAT pathway in premalignant cells. STAT3, once activated, can cause the expression of further genes necessary for cell activation, localisation, survival and proliferation. Inhibition of JAK could therefore be a way of directly affecting malignant cell proliferation, as STAT3 in most malignancies are persistently phosphorylated and thereby stimulated to carry out its function; to sustain cell proliferation and block apoptosis.
For reference, STAT3 is a member of the STAT protein family and is switched on, via phosphorylation, by receptor-associated Janus kinases (JAK), a type of tyrosine kinase, and together they form homo-/heterodimers that translocate to the cell nucleus and act as transcription activators. STAT3 mediates the expression of a variety of genes and therefore is integral to many cellular processes, as mentioned above, such as cell growth and apoptosis, and thus they can promote oncogenesis by being over-active in the different signalling pathways it is involved in.
Itacitinib has not yet been approved by the U.S. Food and Drug Administration (FDA) for any clinical indication but has been developed as potential treatments for myelofibrosis (MF), rheumatoid arthritis (RA), psoriasis, graft-versus-host disease (GVHD), B cell malignancies and solid tumours like HCC. It is a small molecule selective inhibitor of JAK1 thereby preventing its phosphorylation of STAT proteins, particularly STAT3, resulting in a decrease in the expression of genes responsible for cell activation, localisation, survival and proliferation
- Conditions
- Advanced Hepatocellular Carcinoma
- Being tested
- Itacitinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ItacitinibDrug
Also called INCB039110
Novel and small molecule selective inhibitor of JAK1
| Study group | Role | What they receive |
|---|---|---|
| Itacitinib | Experimental | Itacitinib (INCB039110) - novel and small molecule selective inhibitor of JAK1 Receives: Drug: Itacitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Assess the Safety and Tolerability of Itacitinib in Patients With HCC: Adverse Events
Assessment of adverse events relating to experimental drug intake according to the Common Terminology Criteria for Adverse Events (CTCAE) V4.03.
An adverse event (AE) is any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which dose not necessarily have a casual relationship with this treatment. An AE can therefore be any unfavourable and unintended (including an abnormal laboratory finding), symptoms, or disease temporally associated with the use of an investigational medicinal project (IMP), whether or not considered related to the IMP.
Treatment-related adverse events (TrAE) are AEs that are possibly, probably, or likely related to the IMP. Here, TrAEs are reported.
Measured: Throughout study completion, up to 1 year
To Assess Efficacy of Itacitinib by Overall Response Rate: Objective Response Rate (ORR)
The Response Evaluation Criteria in Solid Tumours (RECIST) criteria v1.1. classifies response based on the assessment of target and non-target lesions on CT scans as:
- Complete Response (CR): requires all of:
- disappearance of all target and non-target lesions
- pathological lymph nodes must have reduced to <10 mm in short axis
- no new lesions
- Partial Response (PR): requires all of:
- at least 30% decrease in sum of diameters (SOD) of target lesions compared to baseline sum diameters
- non-progressive disease of non-target lesions
- no new lesions
- Progressive Disease (PD): either one of:
- any new lesions
- at least 20% relative and 5 mm absolute increase of SOD of target lesions compared to smallest SOD ever recorded for the patient
- Stable Disease (SD): not meeting criteria for PD or PR.
Measured: Throughout study completion, up to 1 year
Secondary outcomes (2)
Efficacy of Itacitinib by Progression Free Survival
Progression free survival (PFS), defined as time from study entry to first evidence of disease progression assessed by RECIST or death due to any cause.
Measured: Throughout study completion, up to 1 year
Efficacy of Itacitinib by Overall Survival
Overall survival (OS), defined as time from study entry to death due to any cause.
Measured: Throughout study completion, up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2020
- Study start3 Dec 2018
- Primary completion7 Apr 2023
- Study completion7 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Incyte Biosciences UK
- Responsible party
- Sponsor
- Investigators
- Rohini Sharma, Prof., Principal investigator, Professor Clinical Pharmacology and Medical Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04358185
- Sponsor's protocol ID
- 237279
- Other IDs
- 2017-004437-81, 2017
- Acronym
- JAKaL
- Status last verified
- Apr 2026
- First submitted
- 17 Apr 2020
- Last updated
- 4 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Troiani A, Martinez M, Ward C, Benartzi CW, Pinato DJ, Sharma R. Safety and efficacy of itacitinib, a selective JAK1 inhibitor, in advanced hepatocellular cancer: Phase 1b trial (JAKAL). Future Oncol. 2024;20(36):2839-2847. doi: 10.1080/14796694.2024.2396795. Epub 2024 Sep 16.
PubMed 39283290
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Study of Itacitinib, a JAK1 Inhibitor, in Advanced Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT04358185
- Acronym / sponsor ID
- JAKaL / 237279
- Conditions
- Advanced Hepatocellular Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Incyte Biosciences UK
- Study start
- 3 Dec 2018 (actual)
- Primary completion
- 7 Apr 2023 (actual)
- Study completion
- 7 Apr 2023 (actual)
- First posted
- 24 Apr 2020 (actual)
- Results
- Posted 4 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research will assess the effects of Itacitinib as a second line treatment for patients with advanced inflammatory hepatocellular carcinoma (HCC), a type of liver cancer. Itacinib is a protein inhibitor of the tyrosine kinase, JAK1, which is believed to enable cancer cells to metastasise to other parts of the body.
Detailed description
JAKaL is a single arm phase Ib study evaluating the effect of Itacitinib in 25 patients with advanced HCC.
Many patients diagnosed with HCC will have advanced disease where only palliative care is offered to them, this could account for the relatively low reported 5-year survival rate of approximately 10%. There are a number of epidemiological and pre-clinical studies that have investigated the role of chronic inflammatory conditions in the development of HCC and these provide evidence that inflammation promotes malignant transformation. The production of tumour-promoting cytokines by inflammatory cells can activate transcription factors, such as STAT3 via the JAK/STAT pathway in premalignant cells. STAT3, once activated, can cause the expression of further genes necessary for cell activation, localisation, survival and proliferation. Inhibition of JAK could therefore be a way of directly affecting malignant cell proliferation, as STAT3 in most malignancies are persistently phosphorylated and thereby stimulated to carry out its function; to sustain cell proliferation and block apoptosis.
For reference, STAT3 is a member of the STAT protein family and is switched on, via phosphorylation, by receptor-associated Janus kinases (JAK), a type of tyrosine kinase, and together they form homo-/heterodimers that translocate to the cell nucleus and act as transcription activators. STAT3 mediates the expression of a variety of genes and therefore is integral to many cellular processes, as mentioned above, such as cell growth and apoptosis, and thus they can promote oncogenesis by being over-active in the different signalling pathways it is involved in.
Itacitinib has not yet been approved by the U.S. Food and Drug Administration (FDA) for any clinical indication but has been developed as potential treatments for myelofibrosis (MF), rheumatoid arthritis (RA), psoriasis, graft-versus-host disease (GVHD), B cell malignancies and solid tumours like HCC. It is a small molecule selective inhibitor of JAK1 thereby preventing its phosphorylation of STAT proteins, particularly STAT3, resulting in a decrease in the expression of genes responsible for cell activation, localisation, survival and proliferation
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Itacitinib | Experimental | Drug: ItacitinibItacitinib (INCB039110) - novel and small molecule selective inhibitor of JAK1 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Aged 18 or over
- Diagnosis of hepatocellular carcinoma. If primary diagnosis of HCC: diagnosis based on the following criteria:
- Child-Pugh A and B up to 7 points (in patients receiving anticoagulant therapy; Child-Pugh score up to 5 points; INR category not regarded for calculation of the Child-Pugh score)
- Progression or intolerance to first line therapy - N.B: Date of patients last dose of therapy must be more than 28 days before enrolment into this study.
- ECOG Performance status 0, 1 or 2.
Key exclusion criteria (12 listed)
- Previous treatment with:
- Serious concurrent medical or psychiatric illness, including serious active infection
- Uncontrolled ascites
- Uncontrolled hypertension
- History of organ transplant (including prior liver transplant)
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 |
|---|---|---|
| ItacitinibAlso: INCB039110Novel and small molecule selective inhibitor of JAK1 | Drug | Itacitinib |
Primary outcome
To Assess the Safety and Tolerability of Itacitinib in Patients With HCC: Adverse Events
Time frame: Throughout study completion, up to 1 year
Assessment of adverse events relating to experimental drug intake according to the Common Terminology Criteria for Adverse Events (CTCAE) V4.03. An adverse event (AE) is any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which dose not necessarily have a casual relationship with this treatment. An AE can therefore be any unfavourable and unintended (including an abnormal laboratory finding), symptoms, or disease temporally associated with the use of an investigational medicinal project (IMP), whether or not considered related to the IMP. Treatment-related adverse events (TrAE) are AEs that are possibly, probably, or likely related to the IMP. Here, TrAEs are reported.
To Assess Efficacy of Itacitinib by Overall Response Rate: Objective Response Rate (ORR)
Time frame: Throughout study completion, up to 1 year
The Response Evaluation Criteria in Solid Tumours (RECIST) criteria v1.1. classifies response based on the assessment of target and non-target lesions on CT scans as: * Complete Response (CR): requires all of: * disappearance of all target and non-target lesions * pathological lymph nodes must have reduced to <10 mm in short axis * no new lesions * Partial Response (PR): requires all of: * at least 30% decrease in sum of diameters (SOD) of target lesions compared to baseline sum diameters * non-progressive disease of non-target lesions * no new lesions * Progressive Disease (PD): either one of: * any new lesions * at least 20% relative and 5 mm absolute increase of SOD of target lesions compared to smallest SOD ever recorded for the patient * Stable Disease (SD): not meeting criteria for PD or PR.
2 secondary outcomes
Efficacy of Itacitinib by Progression Free Survival
Time frame: Throughout study completion, up to 1 year
Efficacy of Itacitinib by Overall Survival
Time frame: Throughout study completion, up to 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 39283290Troiani A, Martinez M, Ward C, Benartzi CW, Pinato DJ, Sharma R. Safety and efficacy of itacitinib, a selective JAK1 inhibitor, in advanced hepatocellular cancer: Phase 1b trial (JAKAL). Future Oncol. 2024;20(36):2839-2847. doi: 10.1080/14796694.2024.2396795. Epub 2024 Sep 16.
- 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. This study is not recruiting at the moment.
Rohini Sharma, Prof. principal investigator
Professor Clinical Pharmacology and Medical Oncology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Itacitinib in people with Advanced Hepatocellular Carcinoma, run by Imperial College London at 1 site in United Kingdom.
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 15 inclusion and 12 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: finished, as of the sponsor's last update on 4 May 2026. 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 United Kingdom. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To Assess the Safety and Tolerability of Itacitinib in Patients With HCC: Adverse Events (time frame: Throughout study completion, up to 1 year). The study lists 2 primary outcomes in all. 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 NCT04358185, which also lists 1 linked publication.
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 4 May 2026.