Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as INCB039110
itacitinib · 15 trials · 27 indications
Defined as the percentage of participants demonstrating a complete response (CR), very good partial response (VGPR), or partial response (PR).
An adverse event was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug-related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment.
A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grades 1 through 5. The investigator made an assessment of intensity for each AE and SAE reported during the study and assigned it to 1 of the following categories: Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.
SRR was defined as the percentage of participants who had a reduction in spleen volume (by imaging) of at least 35% when compared with Baseline.
The ASBMT CRS Consensus Grading Criteria was used to assess the severity of CRS. Grade 2 CRS: temperature ≥38°C not attributable to any other cause, defined as fever; hypotension not requiring vasopressors, and/or; hypoxia requiring low-flow nasal cannula (oxygen delivered at ≤6 liters/minute) or blow-by. Grade 3 CRS: fever; hypotension requiring one vasopressor with or without vasopressin, and/or; hypoxyia requiring high-flow nasal cannula (oxygen delivered at \>6 liters/minute), facemask, nonrebreather mask, or Venturi mask. Grade 4 CRS: fever; hypotension requiring multiple vasopressors (excluding vasopressin), and/or; hypoxia requiring positive pressure (e.g., continuous positive airway pressure \[CPAP\], bilevel intermittent positive air pressure \[BiPAP\], intubation, mechanical ventilation).
Spleen volume was measured using magnetic resonance imaging (MRI) or CT scan in participants who were not candidates for MRI or when MRI was not readily available. The MRIs or CTs were read in the central imaging laboratory. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the technique of least squares. The same method (MRI or CT) was used for a given participant unless a new contraindication to the use of MRI (eg, pacemaker insertion) occurred. A positive value indicates an increase in spleen volume and a negative value indicates a decrease in spleen volume.
Spleen volume was measured using MRI or CT scan in participants who were not candidates for MRI or when MRI was not readily available. The MRIs or CTs were read in the central imaging laboratory. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the technique of least squares. The same method (MRI or CT) was used for a given participant unless a new contraindication to the use of MRI (eg, pacemaker insertion) occurred. A positive value indicates an increase in spleen volume and a negative value indicates a decrease in spleen volume.
Failure to engraft will be defined as failure to achieve absolute neutrophil count \>500 for 3 days by day 35.
-Incidence of acute grade III-IV GVHD will be assessed using Mount Sinai Acute GvHD International Consortium (MAGIC) criteria. Attempts should be made to confirm the diagnosis pathologically by biopsy of target organ(s).
Per CTCAE 5.0
Defined as any adverse event reported for the first time or worsening of a pre-existing event after first dose of study drug.
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and until 30 days after the last dose of study drug.
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and until 30 days after the last dose of study drug. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: life-threatening consequences; urgent intervention indicated.
A DLT was defined as the occurrence of any protocol-defined toxicities occurring up to and including Study Day 28, except those with a clear alternative explanation (e.g., disease progression) or transient (≤72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. All DLTs were assessed by the investigator using Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria. In order to be included in the tolerability review, subjects must have received the cohort-specific dose of INCB039110 and ibrutinib for at least 75% of the days during the 28-day surveillance period or have experienced a DLT.
CR: (1) target nodes/nodal masses of lymph nodes/extralymphatic sites regressed to ≤1.5 centimeters (cm) in the longest dimension transverse diameter of lesion (LDi); (2) absence of non-measured lesions; (3) organ enlargement regressed to normal; (4) no new lesions; (5) normal bone marrow morphology; if indeterminate, immunohistochemistry negative. PR: (1) lymph nodes/extralymphatic sites: ≥50% decrease in the sum of the product of perpendicular diameters for multiple lesions of up to 6 target measurable nodes/extranodal sites; if lesion is too small to measure on computed tomography, assign 5 millimeters (mm) × 5 mm as default; if no longer visible, 0 mm × 0 mm. For node \>5 mm × 5 mm but smaller than normal, use actual measurement; (2) absent/regressed non-measured lesions, no increase; (3) organ enlargement; spleen regressed by \>50% in length beyond normal; (4) no new lesions.
ORR defined as the percentage of subjects who have a confirmed best overall response of complete response (CR) or partial response (PR).
| Arm | Type | Description |
|---|---|---|
| Itacitinib | EXPERIMENTAL | Itacitinib plus corticosteroids |
| Placebo | PLACEBO_COMPARATOR | Matching placebo plus corticosteroids |
| Part 1 : Dose Escalation of itacitinib | EXPERIMENTAL | Participants will be dosed at different dose levels with a maximum of up to 9 participants per dose level. |
| Part 2 : Dose Expansion of itacitinib | EXPERIMENTAL | Participants will be dosed at the recommended Phase 2 dose (RP2D) identified in Part 1. |
| Part 1: Open Label Itacitinib Once Daily | EXPERIMENTAL | During Part 1, all participants receive itacitinib 200mg once daily (open label) for 30 days. The study population will include participants receiving any approved IEC for an approved indication. |
| Part 2: Double-Blind Itacitinib Twice Daily | EXPERIMENTAL | During Part 2, participants will be randomized to receive itacitinib 200mg or placebo twice daily for 30 days. The study population also includes participants who are receiving Yescarta for relapsed or refractory large B-cell lymphoma or follicular lymphoma. |
| Cohort A | EXPERIMENTAL | Participants with MF who were tolerating a ruxolitinib dose of less than 20 milligrams (mg) daily with no dose increase or no dose modification in the 8 weeks before screening visit received a combination of the itacitinib at the dose of 200 mg, orally, once daily (QD) and ruxolitinib, orally, twice daily (BID) at their previous stable dose (must had been \< 20 mg daily). Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment are met. |
| Cohort B | EXPERIMENTAL | Participants with MF who progressed after initial reduction in spleen with ruxolitinib treatment, progressed or discontinued for hematologic toxicities received treatment with itacitinib alone at the dose of 600 mg QD. Participants continued study treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other Protocol-specified criteria to stop treatment are met. |
| itacitinib 100 mg | EXPERIMENTAL | itacitinib 100 mg twice a day |
| itacitinib 200 mg | EXPERIMENTAL | itacitinib 200 mg twice a day |
| itacitinib 300 mg | EXPERIMENTAL | itacitinib 300 mg once a day |
| itacitinib 400 mg | EXPERIMENTAL | itacitinib 400 mg once a day |
| itacitinib 600 mg | EXPERIMENTAL | itacitinib 600 mg once a day |
| 100 mg QD Itacitinib | EXPERIMENTAL | - |
| 100 mg QD Placebo | EXPERIMENTAL | - |
| 200 mg QD Itacitinib | EXPERIMENTAL | - |
| 200 mg QD Placebo | EXPERIMENTAL | - |
| 200 mg BID Itacitinib | EXPERIMENTAL | - |
| 200 mg BID Placebo | EXPERIMENTAL | - |
| 600 mg once a day Itacitinib | EXPERIMENTAL | - |
| 600 mg once a day Placebo | EXPERIMENTAL | - |
| Itacitinib 400 mg twice a day | EXPERIMENTAL | Itacitinib 400 mg twice a day |
| Itacitinib 400 mg placebo twice a day | PLACEBO_COMPARATOR | Itacitinib 400 mg placebo twice a day |
| Itacitinib 100 mg twice a day | EXPERIMENTAL | This dose group will be studied twice during the study. |
| Itacitinib 100 mg placebo twice a day | PLACEBO_COMPARATOR | This dose group will be studied twice during the study. |
| Itacitinib 100mg once a day | EXPERIMENTAL | Itacitinib 100mg once a day |
| Itacitinib 100 mg placebo once a day | PLACEBO_COMPARATOR | Itacitinib 100 mg placebo once a day |
| Itacitinib 200 mg twice a day | EXPERIMENTAL | Itacitinib 200 mg twice a day |
| Itacitinib 200 mg placebo twice a day | PLACEBO_COMPARATOR | Itacitinib 200 mg placebo twice a day |
| Itacitinib 300 mg once a day | EXPERIMENTAL | Itacitinib 300 mg once a day |
| Itacitinib 300 mg placebo once a day | PLACEBO_COMPARATOR | Itacitinib 300 mg placebo once a day |
| Itacitinib 600 mg once a day | EXPERIMENTAL | Itacitinib 600 mg once a day |
| Itacitinib 600 mg placebo once a day | PLACEBO_COMPARATOR | Itacitinib 600 mg placebo once a day |
| Pilot Study: Itacitinib | EXPERIMENTAL | * Will undergo institutionally standard myeloablative or reduced intensity chemotherapy or chemoradiotherapy * Stem cell transplantation on Day 0 * Itacitinib 200 mg/day from Day -3 to Day 100. After Day 100, for patients at a dose of 200 mg daily, reduce to 100 mg daily for 1 month, then every other day for one month, then discontinue OR after day 100, for patients already dose reduced to 100 mg daily, reduce to 100 mg every other day then discontinue OR after day 100, for patients on study drug hold, discontinue permanently * To address concerns of engraftment failure using itacitinib throughout the transplant period, for the first three patients the investigators will consent the donor for a second CD34+ collection to use as a rescue in the case of engraftment failure. |
| Expansion Phase: Itacitinib | EXPERIMENTAL | * Will undergo institutionally standard myeloablative or reduced intensity chemotherapy or chemoradiotherapy * Stem cell transplantation on Day 0 * Itacitinib 200 mg/day from Day -3 to Day 180. After Day 180, for patients at a dose of 200 mg daily, reduce to 100 mg daily for 1 month, then every other day for one month, then discontinue OR after day 180, for patients already dose reduced to 100 mg daily, reduce to 100 mg every other day then discontinue OR after day 180, for patients on study drug hold, discontinue permanently |
| Donors | NO_INTERVENTION | -Donors were consented for the patients enrolled in the Safety Lead-In Phase (planned 3 patients). Donors were consented for a second CD34+ collection to use as a rescue in the case of engraftment failure and for collection of a research blood specimen prior to mobilization. |
| ASTX727 + itacitinib | EXPERIMENTAL | ASTX727 and itacitinib will be taken by mouth |
| ASTX727 + ruxolitinib | EXPERIMENTAL | ASTX727 and ruxolitinib will be taken by mouth |
| Itacitinib + corticosteroids | EXPERIMENTAL | Itacitinib administered in combination with corticosteroids. |
| itacitinib + ibrutinib | EXPERIMENTAL | - |
| Itacitinib + osimertinib | EXPERIMENTAL | - |
| pembrolizumab + itacitinib | EXPERIMENTAL | Part 1a Group A will utilize an open-label 3+3 dose-escalation design based on observing each dose level for a period of 21 days. Part 1b Group A-1 and Group A-2 will evaluate the MTD or PAD of itacitinib in combination with pembrolizumab in subjects with select solid tumors. |
| pembrolizumab + INCB050465 | EXPERIMENTAL | Part 1a Group B will utilize an open-label 3+3 dose-escalation design based on observing each dose level for a period of 21 days. Part 1b Group B-1 and Group B-2 will evaluate the MTD or PAD of INCB050465 in combination with pembrolizumab in subjects with select solid tumors. Part 2 will evaluate the combination of INCB050465 in combination with pembrolizumab in subjects with small cell lung cancer, non-small lung cancer and urothelial cancer. |
| Itacitinib (200 mg) | EXPERIMENTAL | Itacitinib (200 mg) + prednisone or methylprednisolone (corticosteroids) |
| Itacitinib (300 mg) | EXPERIMENTAL | Itacitinib (300 mg) + prednisone or methylprednisolone (corticosteroids) |
| itacitinib, gemcitabine, nab-paclitaxel, filgrastim | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Itacitinib | DRUG | Itacitinib at the protocol-defined dose administered orally once daily (QD) plus corticosteroids. |
| Placebo | DRUG | Matching placebo tablets administered orally once daily (QD) plus corticosteroids. |
| Prednisone | DRUG | Oral prednisone may be used to begin standard corticosteroid background treatment at the investigator's discretion, at a dose equivalent to methylprednisolone 2 mg/kg per day. |
| Methylprednisolone | DRUG | Methylprednisolone 2 mg/kg IV daily (or prednisone equivalent) or at a dose appropriate for the severity of disease as background treatment. |
| Immune effector cell therapy | DRUG | Participants will receive IEC therapy that is approved by the health authority in the country where the study is being conducted for any approved hematologic indication. |
| Yescarta | BIOLOGICAL | Eligible participants are receiving Yescarta (An infusion of chimeric antigen receptor (CAR)-transduced autologous T cells) for relapsed or refractory larbe B-cell lymphoma or follicular lymphoma intravenously. |
| Ruxolitinib | DRUG | Ruxolitinib self-administered orally at the stable dose of \< 20 mg daily established before entering the study. |
| Itacitinib Placebo | DRUG | - |
| Stem cell transplantation | PROCEDURE | Standard of care |
| Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) | OTHER | * Screening, day 14, day 28, day 42, day 74, day 100, taper period, and follow-up (pilot study) * Screening, day 14, day 28, day 42, day 74, day 100, day 180, taper period, and follow-up period (expansion study) |
| Human Activity Profile | OTHER | * Screening, day 14, day 28, day 42, day 74, day 100, taper period, and follow-up (pilot study) * Screening, day 14, day 28, day 42, day 60, day 74, day 100, day 180, taper period, and follow-up period (expansion study) |
| ASTX727 | DRUG | Taken by mouth daily during days 1-5 of every 28-day cycle. |
| Corticosteroid | DRUG | Either oral prednisolone or intravenous methylprednisolone at the investigator's discretion. |
| ibrutinib | DRUG | - |
| Osimertinib | DRUG | Osimertinib 80 mg once daily (QD) |
| Pembrolizumab | DRUG | Pembrolizumab 200 mg IV Q3W. |
| INCB050465 | DRUG | INCB050465 tablets administered orally once daily. |
| Itacitinib (200 mg) | DRUG | - |
| Itacitinib (300 mg) | DRUG | - |
| prednisone or methylprednisolone (corticosteroids) | DRUG | All subjects will receive prednisone 2.5 mg/kg per day PO (or methylprednisolone 2 mg/kg IV daily) on Days 1 through 5. Subjects will be tapered as tolerated beginning on Day 6 to no less than 0.25 mg/kg per day PO (or methylprednisolone 0.2 mg/kg per day) by Day 28. After Day 28, corticosteroids should be tapered according to institutional guidelines to attain ≤ prednisone 0.2 mg/kg per day (or ≤ methylprednisolone 0.16 mg/kg per day) by Day 56. |
| Gemcitabine | DRUG | - |
| nab-paclitaxel | DRUG | - |
| filgrastim | DRUG | - |
Inclusion Criteria: * Has undergone 1 allo-HSCT from any donor (related or unrelated with any degree of HLA matching) and any donor source (bone marrow, peripheral blood stem cells, or cord blood) for a hematologic malignancy or disorder. Recipients of myeloablative and reduced-intensity conditioni...
Top 4 of 6 competitors
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Sanofi SA Sponsored ADR | SNY | 5 | PHASE3 | Belumosudil |
| Incyte Corporation | INCY | 10 | PHASE3 | INCA034176, Ruxolitinib, Axatilimab |
| Johnson & Johnson | JNJ | 1 | PHASE3 | Ibrutinib |
| Syndax Pharmaceuticals Inc | SNDX | 1 | PHASE2 | Axatilimab |
Itacitinib is an investigational small molecule developed by Incyte Corporation for immunology and oncology indications. It has been studied in acute graft-versus-host disease, cytokine release syndrome, myelofibrosis, myelodysplastic syndromes, acute myelogenous leukemia, and other cancers. It is not approved and remains in clinical development.
Itacitinib targets JAK1, a Janus kinase enzyme. It acts as a JAK1 inhibitor, meaning it blocks signaling through that kinase. This mechanism underlies its study in immune-mediated conditions such as graft-versus-host disease and cytokine release syndrome, where JAK1-dependent inflammatory signaling is involved.
Itacitinib is developed by Incyte Corporation, which trades on Nasdaq under the ticker INCY. Incyte is the sponsor of the clinical trials evaluating the drug across immunology and oncology indications.
Itacitinib is investigational and remains in clinical development, with trials conducted in Phase 1 and Phase 2. It is not FDA approved. Reported studies include Phase 2 trials in myelofibrosis and cytokine release syndrome prevention, and Phase 1 trials in MDS/MPN overlap syndromes and post-transplant prophylaxis.
Itacitinib has been studied in trials including NCT04629508 (LIMBER-213) in myelofibrosis, NCT04071366 for prevention of cytokine release syndrome after immune effector cell therapy, NCT03755414 for graft-versus-host disease and cytokine release syndrome prophylaxis after haploidentical transplant, and NCT04061421 (ABNL-MARRO) in MDS/MPN overlap syndromes, which is recruiting.