Itacitinib in Advanced Hepatocellular Carcinoma

NCT04358185 | Completed Phase 1 Results DMC

• 2 other identifiers: 2372792017-004437-81
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Throughout study completion, up to 1 year

Secondary Outcomes (2)

• Efficacy of Itacitinib by Progression Free Survival

  Throughout study completion, up to 1 year

• Efficacy of Itacitinib by Overall Survival

  Throughout study completion, up to 1 year

Other Outcomes (2)

• Translational Studies 2

  Throughout study completion, up to 1 year

• Correlation of JAK1 Mutations With Treatment

  Throughout study completion, up to 1 year

Study Arms (1)

Itacitinib

EXPERIMENTAL

Itacitinib (INCB039110) - novel and small molecule selective inhibitor of JAK1

Drug: Itacitinib

Interventions

Itacitinib DRUG

Novel and small molecule selective inhibitor of JAK1

Also known as: INCB039110

Itacitinib

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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
• \. 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

Sponsors & Collaborators

• Imperial College London: lead
• Incyte Biosciences UK: collaborator

Study Sites (1)

Imperial College Healthcare NHS Trust

London, W12 0HS, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 39283290 BACKGROUND

MeSH Terms

Interventions

itacitinib; INCB039110

Results Point of Contact

• Title: Professor Rohini Sharma
• Organization: Imperial College London

r.sharma@imperial.ac.uk

02033131362

Study Officials

• Rohini Sharma, Prof.

  Professor Clinical Pharmacology and Medical Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2020
• First Posted: April 24, 2020
• Study Start: December 3, 2018
• Primary Completion: April 7, 2023
• Study Completion: April 7, 2023
• Last Updated: May 4, 2026
• Results First Posted: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)