JAKaL
Research type
Research Study
Full title
A phase Ib study of INCB039110, a JAK1 inhibitor, in advanced hepatocellular carcinoma
IRAS ID
237279
Contact name
R Sharma
Contact email
Sponsor organisation
Imperial College London
Eudract number
2017-004437-81
Duration of Study in the UK
3 years, 9 months, 31 days
Research summary
Research Summary:
This is a single arm phase Ib study to evaluate the effect of Itacitinib (a JAK1 inhibitor) in -25 patients with advanced HCC where we are trying to assess the safety and tolerability of Itacitinib in patients with advanced hepatocellular carcinoma (HCC). Eligible patients will receive Itacitinib every 400mg QD until disease progression, unacceptable toxicities or withdrawal of consent.
We would also like to assess the efficacy of Itacitinib by overall response rate (ORR)Summary of Results:
Study Title: Phase Ib study of itacitinib, a selective JAK1 inhibitor, for the management of advanced stage hepatocellular cancer after failure of first line therapy.
Hepatocellular carcinoma (HCC) develops on a background of long-term inflammation of the liver, which may be caused by excessive alcohol use, viral infections and dysfunction of the metabolism. Long-term inflammation activates signalling pathways within our cells, which can result in transformation into cancer (or ‘malignant’) cells and tumour growth. One of these key pathways is called the ‘JAK/STAT’ pathway. Itacitinib is a drug that targets ‘JAK1’, a protein involved in the JAK/STAT pathway. It works by blocking JAK1 activity, which can decrease activity of the pathway and have anti-tumour effects, extending survival in some patients with HCC.
Combination immunotherapies are the main treatment option for patients with HCC, however a high proportion of patients will eventually see progression of their disease, and there is limited amount of data available for second line treatments. Additionally, these second line treatments are only suitable for patients who still have maintained good function of their liver, with no established options for patients with impaired liver function.
The JAKaL study aimed to evaluate whether itacitinib was a safe and tolerable treatment for patients with advanced HCC that have already received a first line of treatment. It also evaluated whether the treatment showed any efficacy.
19 patients received treatment in the trial, receiving 400mg of itacitinib daily for 28-day cycles. Participants continued to receive treatment until their disease progressed, they experienced unacceptable side effects, withdrew their consent to participate, or passed away. Participants were observed for any dose-limiting toxicities (DLTs). DLTs are severe adverse reactions to a treatment that mean it is not safe to increase the dose any further in a clinical trial. Four episodes of thrombocytopaenia (low platelet count, a type of blood cell that helps blood to clot) occurred in two patients, resulting in them having to discontinue their treatment. Four participants (21%) had to have their dose of study treatment reduced. Two developed thrombocytopaenia and one developed raised liver enzymes, which were related to the study treatment; one participant developed acute liver decompensation (a severe deterioration in liver function), which was not related to the study treatment.
Overall, 74% of participants experienced a treatment-related adverse reaction. The most frequent adverse reactions were thrombocytopenia in 31% of participants, fatigue in 26% and palmar-plantar erythrodysesthesia syndrome (‘hand-foot syndrome’, a skin reaction to certain types of chemotherapy) in 26%.
Efficacy of the treatment was by measured by analysing Progression-Free Survival (PFS) and Overall Survival (OS). PFS is defined as the length of time after a treatment that a patient lives with a disease before the disease progresses, or worsens. The median PFS observed was 3.5 months. OS is defined as the length of time a patient lives after a treatment, and a median of 7.4 months survival was observed in this study.
Efficacy of the treatment was also measured by assessing any disease response, using CT scans of the chest abdomen and pelvis every 8 weeks, until the treatment was discontinued. 47% of participants had Stable Disease, meaning their tumour(s) did not significantly increase or decrease after receiving treatment.
This study has helped researchers show that itacitinib treatment was associated with an improved survival rate . It also showed that the adverse reactions that occurred are consistent with previous studies, however with a higher rate of severe thrombocytopenia.
This study was sponsored by Imperial College London, and was funded by Incyte Biosciences International Sàrl. The study was conducted at Imperial College Healthcare NHS Trust, starting in December 2018 and ending in December 2022 . Patients with hepatocellular carcinoma (HCC) were involved in the design of the study by identifying an unmet clinical need, and with the conduct of the study directly via the HCC clinic at Imperial College Healthcare NHS Foundation Trust.
You can find out more information about this study by visiting clinicaltrials.gov: Study Details | NCT04358185 | Itacitinib in Advanced Hepatocellular Carcinoma | ClinicalTrials.gov, or contacting the Chief Investigator, Professor Rohini Sharma: r.sharma@imperial.ac.uk Thank you to all participants in this study.REC name
Yorkshire & The Humber - Sheffield Research Ethics Committee
REC reference
18/YH/0212
Date of REC Opinion
13 Aug 2018
REC opinion
Further Information Favourable Opinion