Clinical trial NCT06034002: A Study to Evaluate INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms
Official title: A Phase 1, Open-Label, Multicenter Study of INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Myeloproliferative Neoplasms
Keywords: Myeloproliferative Neoplasms
Myelofibrosis
Essential thrombocythemia
CALR mutation
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2023-09-13
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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, 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/Exclusion Criteria may apply.

Primary outcomes:
measure: Number of participants with Dose Limiting Toxicities (DLTs)
timeFrame: Up to 28 days
measure: Number of participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 3 years and 60 days
Secondary outcomes:
measure: Participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF
timeFrame: Up to 3 years and 60 days
measure: Participants With MF: Percentage of participants achieving spleen volume reduction as defined in the protocol
timeFrame: Up to 24 weeks
measure: Participants with symptomatic anemia: Anemia Response as defined in the protocol
timeFrame: Up to 24 weeks
measure: Participants with ET: Response using the revised IWG-MRT and ELN response criteria for ET
timeFrame: Up to 3 years and 60 days
measure: Incidence of AEs, ECGs, vital signs, and clinical laboratory evaluation
timeFrame: Up to 3 years and 60 days
measure: Percentage of participants achieving ≥ 50% reduction from baseline in total symptom score (TSS)
timeFrame: Week 12 and Week 24
measure: Mean change from baseline in TSS
timeFrame: Week 12 and Week 24
measure: Mean change in disease-related allele burden
timeFrame: Up to 3 years and 60 days
measure: Pharmacokinetics Parameter: Cmax of INCA33989 alone or for the combination of INCA033989 with ruxolitinib
timeFrame: Up to 3 years and 60 days
measure: Pharmacokinetics Parameter: Tmax of INCA033989 alone or for the combination of INCA033989 with ruxolitinib
timeFrame: Up to 3 years and 60 days
measure: Pharmacokinetics Parameter: Cmin of INCA33989 alone or for the combination of INCA033989 with ruxolitinib
timeFrame: Up to 3 years and 60 days
measure: Pharmacokinetics Parameter: AUC(0-t) of INCA33989 alone or for the combination of INCA033989 with ruxolitinib
timeFrame: Up to 3 years and 60 days
measure: Pharmacokinetics Parameter: AUC 0-∞ of INCA33989 alone or for the combination of INCA033989 with ruxolitinib
timeFrame: Up to 3 years and 60 days
measure: Pharmacokinetics Parameter: CL/F of INCA33989 alone or for the combination of INCA033989 with ruxolitinib
timeFrame: Up to 3 years and 60 days
measure: Pharmacokinetics Parameter: Vz/F of INCA33989 alone or for the combination of INCA033989 with ruxolitinib
timeFrame: Up to 3 years and 60 days
measure: Pharmacokinetics Parameter: t1/2 of INCA33989 alone or for the combination of INCA033989 with ruxolitinib
timeFrame: Up to 3 years and 60 days
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Institute
state: California
city: Miami
country: United States
facility: University of Miami Health System
state: Florida
city: Westwood
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Icahn School of Medicine At Mount Sinai
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Md Anderson Cancer Center
state: Texas
Study officials:
affiliation: Incyte Corporation
name: Incyte Medical Monitor
role: STUDY_DIRECTOR
References: