Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
INCA033989 · 3 trials · 2 indications
Normalization of platelet and white blood cell (WBC) counts and absence of disease progression as defined in the protocol.
Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.
Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug, including those leading to dose modification or discontinuation.
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. |
| 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. |
| 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 |
| Incyte Corporation | INCY | 2 | PHASE3 | INCA033989, INCB057643, Ruxolitinib |
INCA033989 is an investigational small molecule being developed for essential thrombocythemia and myeloproliferative neoplasms, which are blood cancers in the hematology therapeutic area. It is designed for adults 18 years and older and is being studied both as a monotherapy and in combination with ruxolitinib. It has not been approved by the FDA.
INCA033989 targets mutant CALR, or mutCALR, a mutated form of the calreticulin protein found in certain myeloproliferative neoplasms. By targeting this mutant protein, the drug is designed to act on the disease-causing clone rather than healthy cells. The trials are biomarker selected, meaning participants are chosen based on this mutation.
INCA033989 is being developed by Incyte Corporation, which trades on the Nasdaq under the ticker INCY. Incyte is running the clinical program, including a Phase 3 study in essential thrombocythemia and Phase 1 studies in myeloproliferative neoplasms.
INCA033989 is in Phase 3 development. The Phase 3 trial is a randomized, controlled study comparing INCA033989 with best available therapy in essential thrombocythemia. The program also includes two Phase 1 studies in myeloproliferative neoplasms. INCA033989 is investigational and has not received FDA approval.
INCA033989 is being evaluated in three registered studies. NCT07623200 is a Phase 3 trial versus best available therapy in essential thrombocythemia, recruiting across the United States, Europe, Japan, and other regions. NCT06034002 is a Phase 1 monotherapy and ruxolitinib combination study in myeloproliferative neoplasms in the United States. NCT05936359 is a Phase 1 monotherapy and ruxolitinib combination study in myeloproliferative neoplasms across Australia, Canada, Europe, and Japan.
INCA033989 has received Breakthrough Therapy designation from the FDA. This designation is intended to expedite development and review of drugs that may offer substantial improvement over available therapies for serious conditions. The drug remains investigational and is still in clinical development.