A Study to Evaluate INCA033989 Administered in Participants With Myeloproliferative Neoplasms
- Registration Number
- NCT06034002
- Lead Sponsor
- Incyte Corporation
- 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 in participants with myeloproliferative neoplasms.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 140
- 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.
- 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 HBV/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 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/Exclusion Criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1a Dose Escalation Cohort Disease Group A - with MF INCA033989 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 INCA033989 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 1b: Dose Expansion - with ET INCA033989 INCA033989 will be administered at the RDE(s) identified during Part 1a. Participants with treatment group A (TGA) essential thrombocythemia (ET) will enroll in this group. Part 1b: Dose Expansion - with MF INCA033989 INCA033989 will be administered at the RDE(s) identified during Part 1a. Participants with treatment group A (TGA) myelofibrosis MF will enroll in this group.
- Primary Outcome Measures
Name Time Method 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
Number of participants with TEAEs leading to dose modification or discontinuation Up to 3 years and 60 days Number of participants with TEAEs leading to dose modification or discontinuation.
- Secondary Outcome Measures
Name Time Method 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 MF with symptomatic anemia: Anemia Response Up to 24 weeks For non transfusion-dependent (TD) participants: An Hb increase relative to baseline as defined in the protocol if non-TD at baseline. For TD participants: Achieving transfusion independency (TI) as defined in the protocol.
Participants With ET: Response Rate Up to 3 years and 60 days Defined as the proportion of participants with Complete Response or Partial Response when treated with study drug.
Participants With ET: Mean change from baseline of total symptom score (TSS) Up to 3 years and 60 days Mean change of 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 INCA33989 Up to 3 years and 60 days Defined as maximum observed plasma concentration of INCA33989.
Pharmacokinetics Parameter: Tmax of INCA033989 Up to 3 years and 60 days Defined as the time to reach the maximum plasma concentration of INCA33989.
Pharmacokinetics Parameter: Cmin of INCA33989 Up to 3 years and 60 days Defined as the minimum observed plasma concentration of INCA33989.
Pharmacokinetics Parameter: AUC(0-t) of INCA33989 Up to 3 years and 60 days Defined as the area under the concentration-time curve up to the last measurable concentration of INCA33989.
Pharmacokinetics Parameter: AUC 0-∞ of INCA33989 Up to 3 years and 60 days Defined as the area under the concentration-time curve from 0 to infinity of INCA33989.
Pharmacokinetics Parameter: CL/F of INCA33989 Up to 3 years and 60 days Defined as the apparent oral dose clearance of INCA33989.
Pharmacokinetics Parameter: Vz/F of INCA33989 Up to 3 years and 60 days Defined as the apparent oral dose volume of distribution of INCA33989.
Pharmacokinetics Parameter: t1/2 of INCA33989 Up to 3 years and 60 days Defined as the apparent terminal phase disposition half-life of INCA33989.
Trial Locations
- Locations (14)
City of Hope Medical Center
🇺🇸Duarte, California, United States
Stanford Cancer Institute
🇺🇸Palo Alto, California, United States
University of Miami Health System
🇺🇸Miami, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
The University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Icahn School of Medicine At Mount Sinai
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Md Anderson Cancer Center
🇺🇸Houston, Texas, United States