Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
INCA033989 · 4 trials · 3 indications
Normalization of platelet and white blood cell (WBC) counts and absence of disease progression as defined in the protocol.
Defined as maximum observed plasma concentration of INCA033989.
Defined as area under the concentration-time curve from time zero to time of the last quantifiable concentration (Clast) of INCA033989.
Defined as area under the single-dose concentration-time curve extrapolated to time of infinity of INCA033989.
Defined as adverse events reported for the first time or the worsening of a pre-existing event, occurring after study drug administration.
Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.
Number of participants with TEAEs leading to dose modification or discontinuation.
| Arm | Type | Description |
|---|---|---|
| INCA033989 | EXPERIMENTAL | Administered intravenous (IV) in accordance with the protocol-defined requirements. |
| Best Available Therapy (BAT) | EXPERIMENTAL | Best Available Therapy (BAT) will be selected by the investigator. |
| Cohort 1 | EXPERIMENTAL | INCA033989 will be administered at protocol defined dose administered as a SC injection. |
| Cohort 2 | EXPERIMENTAL | INCA033989 will be administered at protocol defined dose administered as a SC injection. |
| Cohort 3 | EXPERIMENTAL | INCA033989 will be administered at protocol defined dose administered as an IV infusion. |
| Cohort 4 | EXPERIMENTAL | INCA033989 will be administered at protocol defined dose administered as a SC injection. |
| Cohort 5 | EXPERIMENTAL | INCA033989 in combination with a bioavailability enhancer will be administered at protocol defined dose administered as a SC injection. |
| Cohort 6 | EXPERIMENTAL | INCA033989 in combination with a bioavailability enhancer will be administered at protocol defined dose administered as a SC injection. |
| Cohort 7 | EXPERIMENTAL | INCA033989 in combination with a bioavailability enhancer will be administered at protocol defined dose administered as a SC injection. |
| Part 1a Dose Escalation Cohort Disease Group A - with MF | EXPERIMENTAL | INCA033989 will be administered at a protocol defined starting regimen in 28-day cycles to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE\[s\]). Participants with myelofibrosis (MF) will enroll in this group. |
| Part 1a Dose Escalation Cohort Disease Group A - with ET | EXPERIMENTAL | INCA033989 will be administered at a protocol defined starting regimen in 28-day cycles to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE\[s\]). Participants with essential thrombocythemia (ET) will enroll in this group. |
| Part 1a: Dose Escalation Cohort Disease Group B - with TGB-MF SubOpt R | EXPERIMENTAL | INCA033989 will be administered at a protocol defined starting regimen in 28- day cycles and will allow for the evaluation of INCA033989 in combination with ruxolitinib to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE\[s\]). Participants with myelofibrosis (MF) exhibiting suboptimal response (SubOpt R) will enroll in this group. |
| Part 1b: Dose Expansion - with MF | EXPERIMENTAL | INCA033989 will be administered as monotherapy at the RDE(s) identified during Part 1a. Participants with treatment group A (TGA) myelofibrosis MF will enroll in this group. |
| Part 1b: Dose Expansion - with TGB-MF SubOpt R | EXPERIMENTAL | INCA033989 will be administered as an add-on therapy in combination with ruxolitinibat at the RDE(s) identified during Part 1a. Participants with treatment Group B (TGB) MF SubOpt R will enroll in this group. |
| Part 1b: Dose Expansion - with ET | EXPERIMENTAL | INCA033989 will be administered as monotherapy at the RDE(s) identified during Part 1a. Participants with treatment group A (TGA) essential thrombocythemia (ET) will enroll in this group. |
| Part 1c: Dose Expansion | EXPERIMENTAL | INCA033989 will be administered at the dose level found to exhibit an overall positive benefit/risk as monotherapy or as combination therapy with Ruxolitinib. Participants with myelofibrosis (MF) will enroll in this group. The participants enrolled in the monotherapy arm will be offered the option to crossover to combination therapy with ruxolitinib if a suboptimal response to monotherapy is observed after 12 weeks. |
| Name | Type | Description |
|---|---|---|
| INCA033989 | DRUG | Administered intravenous (IV) in accordance with the protocol-defined requirements. |
| Best Available Treatment | DRUG | Best Available Therapy (BAT) will be selected by the investigator. |
| Bioavailability enhancer | DRUG | A bioavailability enhancer will be administered with INCA033989 at protocol defined dose. |
| Ruxolitinib | DRUG | Rux will be administered according to Prescribing Information/SmPC. |
Inclusion Criteria: * Confirmed diagnosis of high-risk ET. * Presence of mutCALR. * Prior treatment with at least 1 cytoreductive therapy. Exclusion Criteria: * Presence of any hematologic malignancy other than ET. * Major bleeding or thrombosis within the last 3 months prior to study enrollment....
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Merck & Co., Inc. | MRK | 3 | PHASE3 | Bomedemstat, Hydroxyurea |
| Incyte Corporation | INCY | 1 | PHASE1 | INCB057643, Ruxolitinib |
INCA033989 is an investigational small molecule being developed by Incyte Corporation for the treatment of myeloproliferative neoplasms and essential thrombocythemia. It is also being studied in healthy participants for pharmacokinetic, safety, and tolerability assessments. The drug is currently in Phase 3 clinical development.
INCA033989 targets mutant calreticulin (mutCALR), a protein involved in the development of certain myeloproliferative neoplasms. By targeting this specific mutant protein, the drug aims to address the underlying driver of the disease. This targeted approach is being evaluated in clinical trials for conditions like essential thrombocythemia.
INCA033989 is being developed by Incyte Corporation, a biopharmaceutical company traded on the NASDAQ under the ticker symbol INCY. Incyte is conducting clinical trials to evaluate the drug's safety and efficacy in patients with myeloproliferative neoplasms and essential thrombocythemia.
INCA033989 is in Phase 3 clinical development for essential thrombocythemia, with a randomized, controlled trial comparing it to best available therapy. It has also received Breakthrough Therapy designation from the FDA. The drug is investigational and not yet approved for any indication.
INCA033989 is being studied in several trials. NCT05936359 and NCT06034002 are Phase 1 studies in myeloproliferative neoplasms, testing the drug alone or with ruxolitinib. NCT07448155 is a Phase 1 study in healthy participants. NCT07623200 is a Phase 3 trial in essential thrombocythemia comparing INCA033989 to best available therapy.
INCA033989 is being developed specifically for essential thrombocythemia, a type of myeloproliferative neoplasm. It is currently in a Phase 3 trial for this condition, where it is being compared to best available therapy. The drug targets mutant calreticulin, which is a driver in some cases of this disease.