What Is Itacitinib?
Itacitinib is a drug currently under investigation in clinical trials for various conditions, primarily those involving immune system responses and certain cancers. It is administered in conjunction with different immunosuppression regimens, suggesting its role in modulating the immune system. For example, it is being studied for its potential to prevent cytokine release syndrome (CRS) in patients receiving approved immune effector cell (IEC) therapy for hematologic malignancies. Itacitinib is also being explored in combination with other therapies, such as CAR-T-cell therapy, where it is given to participants before and after CAR-T-cell infusion to manage immune responses.
Clinical trials for itacitinib began in 2012, with the latest trial starting in 2023. A total of 50 trials have been conducted or are ongoing, involving 2,966 participants. The primary sponsor for these investigations is Incyte Corporation.
Uses and Conditions Under Study
Itacitinib is being investigated for a range of conditions, with a focus on blood cancers, solid tumors, and immune-related disorders. Across 50 clinical trials, it has involved 2,966 participants.
- Blood Cancers and Related Disorders: Itacitinib is being studied for conditions such as Hematologic and Lymphocytic Disorder (3 trials), B-Cell Malignancies (2 trials), MPN (Myeloproliferative Neoplasms) (2 trials), and Secondary Myelofibrosis (2 trials). These conditions involve abnormal growth or function of blood cells, and itacitinib's immune-modulating properties may help manage disease progression or symptoms.
- Solid Tumors: The drug is also under investigation for various solid cancers, including Solid Tumors (3 trials), Non Small Cell Lung Cancer (NSCLC) (2 trials), Breast Cancer (2 trials), and Pancreatic Cancer (2 trials). One study, known as JAKaL, is evaluating itacitinib in 25 patients with advanced Hepatocellular Carcinoma (HCC), a type of liver cancer.
- Immune-Related Conditions: Itacitinib shows promise in managing severe immune responses. It is being studied for Graft-versus-host Disease (GVHD) (2 trials), a complication that can occur after a stem cell or bone marrow transplant. Additionally, it is being assessed for the prevention of Cytokine Release Syndrome (CRS) in patients aged 12 years or older who are undergoing immune effector cell therapy, aiming to reduce potentially life-threatening inflammatory reactions.
Dosing
Itacitinib has been studied in various dosage forms and strengths, primarily for oral administration. Participants in clinical trials have received itacitinib as an oral medication, often referred to as "given by mouth" or "per os." An intravenous (IV) form has also been mentioned in some trial descriptions.
The strengths of itacitinib studied include:
- 100 mg
- 200 mg
- 300 mg
- 400 mg
- 600 mg
Dosing regimens have varied across studies. Some trials have administered itacitinib once daily (QD), such as 200 mg orally once daily for 30 days post-CAR-T-cell therapy, or 300 mg orally every day for 30 days. Other regimens include twice daily (BID) dosing, for example, 200 mg twice daily or 400 mg twice daily. One study explored 200 mg orally once daily for 360 days. Itacitinib has also been investigated in combination with other drugs, such as parsaclisib, where combinations like parsaclisib 20 mg plus itacitinib 300 mg were studied. The drug has been evaluated in participants aged 12 years or older for the prevention of cytokine release syndrome.
Side Effects
In clinical trials involving 795 patients treated with Itacitinib, the most common side effect was thrombocytopenia (low platelet count). 29.1% of patients taking Itacitinib experienced thrombocytopenia, compared to 28.7% on placebo. Other common side effects included:
- Anemia (low red blood cell count): 28.6% of patients on Itacitinib experienced anemia, compared to 25.0% on placebo.
- Pyrexia (fever): 23.3% of patients on Itacitinib experienced pyrexia, compared to 17.9% on placebo.
- Peripheral edema (swelling in limbs): 22.0% of patients on Itacitinib experienced peripheral edema, compared to 22.9% on placebo.
- Diarrhea: 21.1% of patients on Itacitinib experienced diarrhea, compared to 20.8% on placebo.
- Nausea: 20.8% of patients on Itacitinib experienced nausea, compared to 17.9% on placebo.
- Fatigue: 20.6% of patients on Itacitinib experienced fatigue, compared to 19.6% on placebo.
- Hyperglycemia (high blood sugar): 18.6% of patients on Itacitinib experienced hyperglycemia, compared to 22.5% on placebo.
Clinical Trial Results
B-Cell Malignancies (CITADEL-101)
In a Phase 1/2 study (NCT02018861) investigating Itacitinib in combination with Parsaclisib for previously treated B-cell malignancies, specific results were observed for different lymphoma types. For participants with Chronic Lymphocytic Leukemia (CLL), 100.0% of those receiving Parsaclisib 20 mg plus Itacitinib 300 mg achieved an overall response (complete or partial response). The median time to maximum concentration (Tmax) for Itacitinib in combination with Parsaclisib 20/30 mg was 2.0 hours. Treatment-emergent adverse events (TEAEs) were reported in 6 participants receiving Parsaclisib 20 mg + Itacitinib 300 mg and 3 participants receiving Parsaclisib 30 mg + Itacitinib 300 mg.
Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
A study (NCT02760485) evaluated Itacitinib in combination with Ibrutinib for relapsed or refractory DLBCL. In Phase 1, the overall response rate (ORR) was 33.3% for patients on Itacitinib 300 mg daily plus Ibrutinib 560 mg daily, and 57.1% for those on Itacitinib 400 mg daily plus Ibrutinib 560 mg daily. In Phase 2, the ORR for Itacitinib 400 mg daily plus Ibrutinib 560 mg daily was 26.3%, with a durable response rate of 60.0%. The median duration of response was 8.80 months, and median progression-free survival was 3.17 months.
Acute Graft-Versus-Host Disease (aGVHD) (GRAVITAS-301)
The GRAVITAS-301 study (NCT03139604) compared Itacitinib plus corticosteroids to placebo plus corticosteroids for acute GVHD. The overall response rate based on the CIBMTR Response Index was 74.0% for patients receiving Itacitinib plus corticosteroids, compared to 66.4% for those on placebo plus corticosteroids. The median duration of response was 587 days for the Itacitinib group, while it was not available for the placebo group. Median overall survival was 365 days for Itacitinib plus corticosteroids, versus 348.5 days for placebo plus corticosteroids. Failure-free survival was observed in 44.29% of participants in the Itacitinib group, compared to 40.00% in the placebo group.
Myelofibrosis
A study (NCT03144687) explored Itacitinib alone or in combination with low-dose Ruxolitinib for myelofibrosis. At Week 24, patients receiving Itacitinib alone (Cohort B) showed a mean reduction in total symptom score of 4.7 points as measured by the MFSAF v2.0 Symptom Diary, and a mean reduction in spleen length by palpation of 3.6 cm. The percentage change from baseline in spleen volume reduction (SVR) at Week 12 was -24.6% for Itacitinib alone (Cohort B), indicating a reduction in spleen size.
Non-Small Cell Lung Cancer (NSCLC)
In a study (NCT03425006) of Pembrolizumab and Itacitinib for previously untreated, PD-L1 positive metastatic NSCLC, 65% (13 out of 20 participants) achieved a response at 12 weeks according to RECIST 1.1 criteria. Among these 20 participants, 13 participants had a minimum duration of response of 12 weeks. All 20 participants in this arm experienced treatment-related toxicities.
Currently Recruiting Trials
Itacitinib is currently being investigated in several clinical trials, exploring its potential in diverse conditions. These studies aim to understand how itacitinib works, its safety, and its effectiveness in treating specific diseases. Participating in a clinical trial can offer access to investigational treatments and contribute to medical knowledge.
One active Phase 2 study, NCT05757219, is evaluating itacitinib as a pre-modulation treatment for diffuse large B-cell lymphoma (DLBCL). This trial, sponsored by H. Lee Moffitt Cancer Center and Research Institute, is assessing the safety and efficacy of once-daily oral itacitinib in participants with DLBCL who are scheduled to receive axicabtagene ciloleucel (axi-cel) CAR-T cell therapy. The study is seeking to enroll up to 27 participants.
Another Phase 2 study, NCT04789850, is focused on systemic sclerosis. Sponsored by Assistance Publique - Hôpitaux de Paris, this trial is determining whether itacitinib is safe and effective for adults living with this condition. The study plans to include up to 74 adults.
Additionally, a Phase 1/Phase 2 basket study named ABNL-MARRO, identified as NCT04061421, is exploring novel compound combinations for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) overlap syndromes. This international collaboration, led by Michael Savona, is investigating combinations such as ASTX727 with itacitinib, and ASTX727 with ruxolitinib, to advance treatment for these complex blood disorders. This study aims to enroll up to 94 participants.
Where to Participate
Clinical trials for itacitinib are accessible across the United States, with study sites located in four cities across four different states. The top locations currently recruiting participants include Tampa, Florida; Rochester, New York; Portland, Oregon; and Nashville, Tennessee. Each site offers an opportunity for eligible individuals to contribute to the research and potentially benefit from new treatments.
Eligibility criteria for these studies typically require participants to be adults 18 years of age. All genders are welcome to participate. It is important to note that these trials are not open to healthy volunteers and children are not eligible.
Development Timeline
The journey of itacitinib in clinical development began with its first trial in 2012. Since then, the investigational drug has been studied in a comprehensive program, encompassing over 50 trials and enrolling nearly 3,000 participants across various phases. Initial investigations focused on conditions such as IBS-C and hyperphosphatemia, laying the groundwork for its broader application.
Over time, the development pipeline for itacitinib expanded significantly. Research progressed into a wide array of conditions, including various B-cell malignancies, non-small cell lung cancer, breast cancer, and pancreatic cancer. Itacitinib also showed promise in immune-related disorders like graft-versus-host disease (GVHD) and systemic sclerosis, as well as myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS).
The majority of these studies have been in Phase 2 (25 trials), indicating a focus on assessing efficacy and safety in larger patient groups. Phase 1 studies (13 trials) explored initial safety and dosing, while several Phase 1/Phase 2 trials (9 trials) combined these objectives. Incyte Corporation has been a primary driver of this research, sponsoring 27 of the trials, with significant contributions from academic institutions and other sponsors.