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This study is being conducted to evaluate the safety, tolerability, dose-limiting toxicity (DLT) and determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDE) of INCA033989 administered as a Monotherapy or in Combination With Ruxolitinib in participants with myeloproliferative neoplasms.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| INCA033989 | Drug | INCA033989 will be administered at protocol defined dose. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with Dose Limiting Toxicities (DLTs) | Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol. | Up to 28 days |
| Number of participants with Treatment-emergent Adverse Events (TEAEs) | 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. | Up to 3 years and 60 days |
| Measure | Description | Time Frame |
|---|---|---|
| Participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF | Defined as the percentage of participants with Response using the revised IWG-MRT and ELN response criteria. | Up to 3 years and 60 days |
| Participants With MF: Percentage of participants achieving spleen volume reduction as defined in the protocol |
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Inclusion Criteria:
Exclusion Criteria:
Other protocol-defined Inclusion/Exclusion Criteria may apply.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Incyte Corporation Call Center (US) | Contact | 1.855.463.3463 | medinfo@incyte.com | |
| Incyte Corporation Call Center (ex-US) | Contact | +800 00027423 | eumedinfo@incyte.com |
| Name | Affiliation | Role |
|---|---|---|
| Incyte Medical Monitor | Incyte Corporation | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| City of Hope Medical Center | Recruiting | Duarte | California | 91010 | United States | |
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| Label | URL |
|---|---|
| A study to Evaluate INCA033989 Administered in Participants with Myeloproliferative Neoplasms | View source |
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| 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. |
|
| Ruxolitinib | Drug | Rux will be administered according to Prescribing Information/SmPC. |
|
|
Defined as percentage of participants with a protocol defined Spleen Volume Reduction. |
| Up to 24 weeks |
| Participants with symptomatic anemia: Anemia Response as defined in the protocol | Anemia Response as defined by the protocol. | Up to 24 weeks |
| Participants with ET: Response using the revised IWG-MRT and ELN response criteria for ET | Defined as the percentage of participants with Response using the revised IWG-MRT and ELN response criteria. | Up to 3 years and 60 days |
| Incidence of AEs, ECGs, vital signs, and clinical laboratory evaluation | To evaluate the safety of INCA033989. | Up to 3 years and 60 days |
| Percentage of participants achieving ≥ 50% reduction from baseline in total symptom score (TSS) | Defined as the percentage of participants achieving ≥ 50% reduction from baseline in TSS. | Week 12 and Week 24 |
| Mean change from baseline in TSS | Mean change in TSS from baseline. | Week 12 and Week 24 |
| Mean change in disease-related allele burden | Mean change from baseline in disease-related variant allele frequency quantified by targeted NGS and evaluated with myeloid and lymphoid proportion in blood. | Up to 3 years and 60 days |
| Pharmacokinetics Parameter: Cmax of INCA033989 alone or for the combination of INCA033989 with ruxolitinib | Defined as maximum observed plasma concentration of INCA033989 alone or for the combination of INCA033989 with ruxolitinib. | Up to 3 years and 60 days |
| Pharmacokinetics Parameter: Tmax of INCA033989 alone or for the combination of INCA033989 with ruxolitinib | Defined as the time to reach the maximum plasma concentration of INCA033989 alone or for the combination of INCA033989 with ruxolitinib. | Up to 3 years and 60 days |
| Pharmacokinetics Parameter: Cmin of INCA033989 alone or for the combination of INCA033989 with ruxolitinib | Defined as the minimum observed plasma concentration of INCA033989 alone or for the combination of INCA033989 with ruxolitinib. | Up to 3 years and 60 days |
| Pharmacokinetics Parameter: AUC(0-t) of INCA033989 alone or for the combination of INCA033989 with ruxolitinib | Defined as the area under the concentration-time curve up to the last measurable concentration of INCA033989 alone or for the combination of INCA033989 with ruxolitinib. | Up to 3 years and 60 days |
| Pharmacokinetics Parameter: AUC 0-∞ of INCA033989 alone or for the combination of INCA033989 with ruxolitinib | Defined as the area under the concentration-time curve from 0 to infinity of INCA033989 alone or for the combination of INCA033989 with ruxolitinib. | Up to 3 years and 60 days |
| Pharmacokinetics Parameter: CL/F of INCA033989 alone or for the combination of INCA033989 with ruxolitinib | Defined as the apparent oral dose clearance of INCA033989 alone or for the combination of INCA033989 with ruxolitinib. | Up to 3 years and 60 days |
| Pharmacokinetics Parameter: Vz/F of INCA033989 alone or for the combination of INCA033989 with ruxolitinib | Defined as the apparent oral dose volume of distribution of INCA033989 alone or for the combination of INCA033989 with ruxolitinib. | Up to 3 years and 60 days |
| Pharmacokinetics Parameter: t1/2 of INCA033989 alone or for the combination of INCA033989 with ruxolitinib | Defined as the apparent terminal phase disposition half-life of INCA033989 alone or for the combination of INCA033989 with ruxolitinib. | Up to 3 years and 60 days |
| Stanford Cancer Institute |
| Recruiting |
| Palo Alto |
| California |
| 94304 |
| United States |
| University of Miami Health System | Recruiting | Miami | Florida | 33136 | United States |
| The University of Kansas Cancer Center | Recruiting | Westwood | Kansas | 66205 | United States |
| Johns Hopkins Hospital | Recruiting | Baltimore | Maryland | 21287 | United States |
| Dana Farber Cancer Institute | Recruiting | Boston | Massachusetts | 02215 | United States |
| Washington University School of Medicine | Recruiting | St Louis | Missouri | 63108 | United States |
| Icahn School of Medicine At Mount Sinai | Recruiting | New York | New York | 10029 | United States |
| Memorial Sloan Kettering Cancer Center | Recruiting | New York | New York | 10065 | United States |
| Wake Forest Baptist Medical Center | Recruiting | Winston-Salem | North Carolina | 27157 | United States |
| Cleveland Clinic | Recruiting | Cleveland | Ohio | 44195 | United States |
| Vanderbilt University Medical Center | Recruiting | Nashville | Tennessee | 37232 | United States |
| Md Anderson Cancer Center | Recruiting | Houston | Texas | 77030 | United States |
| ID | Term |
|---|---|
| D009196 | Myeloproliferative Disorders |
| D055728 | Primary Myelofibrosis |
| D013920 | Thrombocythemia, Essential |
| ID | Term |
|---|---|
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D001778 | Blood Coagulation Disorders |
| D013922 | Thrombocytosis |
| D001791 | Blood Platelet Disorders |
| D006474 | Hemorrhagic Disorders |
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| ID | Term |
|---|---|
| C540383 | ruxolitinib |
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