Myeloproliferative Neoplasms
Conditions
Keywords
Myeloproliferative Neoplasms, Myelofibrosis, Essential thrombocythemia, CALR mutation
Brief summary
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.
Interventions
DRUGINCA033989
INCA033989 will be administered at protocol defined dose.
DRUGRuxolitinib
Rux will be administered according to Prescribing Information/SmPC.
Sponsors
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Life expectancy \> 6 months. * Willingness to undergo a pretreatment and regular on-study BM biopsies and aspirates (as appropriate to disease). * Existing documentation from a qualified local laboratory of CALR exon-9 mutation. * Participants with MF or ET as defined in the protocol.
Exclusion criteria
* Presence of any hematological malignancy other than ET, PMF, or post-ET MF. * Prior history of major bleeding, or thrombosis within the last 3 months prior to study enrollment. * Participants with laboratory values exceeding the protocol defined thresholds. * Has undergone any prior allogenic or autologous stem-cell transplantation or such transplantation is planned. * Active invasive malignancy over the previous 2 years. * History of clinically significant or uncontrolled cardiac disease. * Active or chronic HBV or active HCV or known history of HIV. * Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, antibody, or hypomethylating agent used to treat the participant's disease, with the exception of ruxolitinib for TGBs only, within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment. * Participants undergoing treatment with G-CSF, GM-CSF, or TPO-R agonists at any time within 4 weeks before the first dose of study treatment. Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Dose Limiting Toxicities (DLTs) | Up to 28 days | Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol. |
| Number of participants with Treatment-emergent Adverse Events (TEAEs) | Up to 3 years and 60 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF | Up to 3 years and 60 days | Defined as the percentage of participants with Response using the revised IWG-MRT and ELN response criteria. |
| Participants With MF: Percentage of participants achieving spleen volume reduction as defined in the protocol | Up to 24 weeks | Defined as percentage of participants with a protocol defined Spleen Volume Reduction. |
| Participants with symptomatic anemia: Anemia Response as defined in the protocol | Up to 24 weeks | Anemia Response as defined by the protocol. |
| Participants with ET: Response using the revised IWG-MRT and ELN response criteria for ET | Up to 3 years and 60 days | Defined as the percentage of participants with Response using the revised IWG-MRT and ELN response criteria. |
| Incidence of AEs, ECGs, vital signs, and clinical laboratory evaluation | Up to 3 years and 60 days | To evaluate the safety of INCA033989. |
| Percentage of participants achieving ≥ 50% reduction from baseline in total symptom score (TSS) | Week 12 and Week 24 | Defined as the percentage of participants achieving ≥ 50% reduction from baseline in TSS. |
| Mean change from baseline in TSS | Week 12 and Week 24 | Mean change in TSS from baseline. |
| Mean change in disease-related allele burden | Up to 3 years and 60 days | Mean change from baseline in disease-related variant allele frequency quantified by targeted NGS and evaluated with myeloid and lymphoid proportion in blood. |
| Pharmacokinetics Parameter: Cmax of INCA033989 alone or for the combination of INCA033989 with ruxolitinib | Up to 3 years and 60 days | Defined as maximum observed plasma concentration of INCA033989 alone or for the combination of INCA033989 with ruxolitinib. |
| Pharmacokinetics Parameter: Tmax of INCA033989 alone or for the combination of INCA033989 with ruxolitinib | Up to 3 years and 60 days | Defined as the time to reach the maximum plasma concentration of INCA033989 alone or for the combination of INCA033989 with ruxolitinib. |
| Pharmacokinetics Parameter: Cmin of INCA033989 alone or for the combination of INCA033989 with ruxolitinib | Up to 3 years and 60 days | Defined as the minimum observed plasma concentration of INCA033989 alone or for the combination of INCA033989 with ruxolitinib. |
| Pharmacokinetics Parameter: AUC(0-t) of INCA033989 alone or for the combination of INCA033989 with ruxolitinib | Up to 3 years and 60 days | 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. |
| Pharmacokinetics Parameter: AUC 0-∞ of INCA033989 alone or for the combination of INCA033989 with ruxolitinib | Up to 3 years and 60 days | Defined as the area under the concentration-time curve from 0 to infinity of INCA033989 alone or for the combination of INCA033989 with ruxolitinib. |
| Pharmacokinetics Parameter: CL/F of INCA033989 alone or for the combination of INCA033989 with ruxolitinib | Up to 3 years and 60 days | Defined as the apparent oral dose clearance of INCA033989 alone or for the combination of INCA033989 with ruxolitinib. |
| Pharmacokinetics Parameter: Vz/F of INCA033989 alone or for the combination of INCA033989 with ruxolitinib | Up to 3 years and 60 days | Defined as the apparent oral dose volume of distribution of INCA033989 alone or for the combination of INCA033989 with ruxolitinib. |
| Pharmacokinetics Parameter: t1/2 of INCA033989 alone or for the combination of INCA033989 with ruxolitinib | Up to 3 years and 60 days | Defined as the apparent terminal phase disposition half-life of INCA033989 alone or for the combination of INCA033989 with ruxolitinib. |
Countries
United States
Contacts
CONTACTIncyte Corporation Call Center (US)
CONTACTIncyte Corporation Call Center (ex-US)
STUDY_DIRECTORIncyte Medical Monitor
Incyte Corporation
Outcome results
None listed