A Study to Evaluate INCA033989 Administered in Participants With Myeloproliferative Neoplasms

Myeloproliferative Neoplasms Clinical Trial

Official title:

A Phase 1, Open-Label, Multicenter Study of INCA033989 in Participants With Myeloproliferative Neoplasms

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06034002
• Other study ID #: INCA33989-102
• Status: Recruiting
• Phase: Phase 1
• Start date: December 4, 2023
• Est. completion date: October 29, 2028

Study information

• Verified date: April 2024
• Source: Incyte Corporation
• Contact: Incyte Corporation Call Center (US)
• Phone: 1.855.463.3463
• Email: medinfo[@]incyte.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: October 29, 2028
• Est. primary completion date: October 29, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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.

Related Conditions & MeSH terms

• Myeloproliferative Disorders
• Myeloproliferative Neoplasms
• Neoplasms

Intervention

Drug:
• INCA033989
INCA033989 will be administered at protocol defined dose.

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Cleveland Clinic	Cleveland	Ohio
United States	City of Hope Medical Center	Duarte	California
United States	Md Anderson Cancer Center	Houston	Texas
United States	University of Miami Health System	Miami	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
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	Stanford Cancer Institute	Palo Alto	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Moffitt Cancer Center	Tampa	Florida
United States	The University of Kansas Cancer Center	Westwood	Kansas
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Up to 3 years and 60 days
Primary	Number of participants with TEAEs leading to dose modification or discontinuation	Number of participants with TEAEs leading to dose modification or discontinuation.	Up to 3 years and 60 days
Secondary	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
Secondary	Participants With MF: Percentage of participants achieving spleen volume reduction as defined in the protocol	Defined as percentage of participants with a protocol defined Spleen Volume Reduction.	Up to 3 years and 60 days
Secondary	Participants with MF with symptomatic anemia: Anemia Response	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.	Up to 3 years and 60 days
Secondary	Participants With ET: Response Rate	Defined as the proportion of participants with Complete Response or Partial Response when treated with study drug.	Up to 3 years and 60 days
Secondary	Participants With ET: Mean change from baseline of total symptom score (TSS)	Mean change of TSS from baseline.	Up to 3 years and 60 days
Secondary	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
Secondary	Pharmacokinetics Parameter: Cmax of INCA33989	Defined as maximum observed plasma concentration of INCA33989.	Up to 3 years and 60 days
Secondary	Pharmacokinetics Parameter: Tmax of INCA033989	Defined as the time to reach the maximum plasma concentration of INCA33989.	Up to 3 years and 60 days
Secondary	Pharmacokinetics Parameter: Cmin of INCA33989	Defined as the minimum observed plasma concentration of INCA33989.	Up to 3 years and 60 days
Secondary	Pharmacokinetics Parameter: AUC(0-t) of INCA33989	Defined as the area under the concentration-time curve up to the last measurable concentration of INCA33989.	Up to 3 years and 60 days
Secondary	Pharmacokinetics Parameter: AUC 0-8 of INCA33989	Defined as the area under the concentration-time curve from 0 to infinity of INCA33989.	Up to 3 years and 60 days
Secondary	Pharmacokinetics Parameter: CL/F of INCA33989	Defined as the apparent oral dose clearance of INCA33989.	Up to 3 years and 60 days
Secondary	Pharmacokinetics Parameter: Vz/F of INCA33989	Defined as the apparent oral dose volume of distribution of INCA33989.	Up to 3 years and 60 days
Secondary	Pharmacokinetics Parameter: t1/2 of INCA33989	Defined as the apparent terminal phase disposition half-life of INCA33989.	Up to 3 years and 60 days