Clinical trial NCT05936359: 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
Ruxolitinib
Myelofibrosis
Essential thrombocythemia
CALR mutation
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2023-07-07
Enrollment: 225
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, and 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 and ET as defined in the protocol.

Exclusion Criteria:

* Presence of any hematological malignancy other than ET, PMF, or post-ET MF.
* Active invasive malignancy over the previous 2 years.
* Active HBV/HCV, HIV.
* History of clinically significant or uncontrolled cardiac disease.
* Has undergone any prior allogenic or autologous stem-cell transplantation or such transplantation is planned.
* Laboratory values outside the Protocol-defined ranges.
* 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.
* Prior history of major bleeding, or thrombosis within the last 3 months prior to study enrollment.
* 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.
* For TGBs only: Undergoing treatment with a potent/strong inhibitor or inducer of CYP 3A4/5 within 14 days or 5 half-lives (whichever is longer) before the first dose of study treatment, or expected to receive such treatment during the study.

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
measure: Number of participants with TEAEs leading to dose modification or discontinuation
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 3 years and 60 days
measure: Participants with MF with symptomatic anemia: Anemia Response
timeFrame: Up to 3 years and 60 days
measure: Participants With ET: Response Rate
timeFrame: Up to 3 years and 60 days
measure: Participants With ET: Mean change from baseline of total symptom score (TSS)
timeFrame: Up to 3 years and 60 days
measure: Mean change in disease-related allele burden
timeFrame: Up to 3 years and 60 days
measure: Pharmacokinetics Parameter: Cmax of INCA33989
timeFrame: Up to 3 years and 60 days
measure: Pharmacokinetics Parameter: Tmax of INCA033989
timeFrame: Up to 3 years and 60 days
measure: Pharmacokinetics Parameter: Cmin of INCA33989
timeFrame: Up to 3 years and 60 days
measure: Pharmacokinetics Parameter: AUC(0-t) of INCA33989
timeFrame: Up to 3 years and 60 days
measure: Pharmacokinetics Parameter: AUC 0-∞ of INCA33989
timeFrame: Up to 3 years and 60 days
measure: Pharmacokinetics Parameter: CL/F of INCA33989
timeFrame: Up to 3 years and 60 days
measure: Pharmacokinetics Parameter: Vz/F of INCA33989
timeFrame: Up to 3 years and 60 days
measure: Pharmacokinetics Parameter: t1/2 of INCA33989
timeFrame: Up to 3 years and 60 days
Other outcomes:
Locations:
city: Herston
country: Australia
facility: Royal Brisbane and Women'S Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Montreal
country: Canada
facility: Hopital Maisonneuve-Rosemont, Montreal, Qc
state: Quebec
city: Odense C
country: Denmark
facility: Odense University Hospital
city: Roskilde
country: Denmark
facility: Sjaellands Universitetshospital
city: Vejle
country: Denmark
facility: Vejle Hospital
city: Bordeaux
country: France
facility: Institut Bergonie
city: Nimes
country: France
facility: Chu Nimes
city: Paris
country: France
facility: Hospital Saint Louis
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
city: Aachen
country: Germany
facility: University Medical Center Rwth Aachen
city: Halle
country: Germany
facility: Universitatsklinikum Halle (Saale)
city: ULM
country: Germany
facility: Universitatsklinikum Ulm
city: Bologna
country: Italy
facility: Aou Policlinico S. Orsola-Malpighi Bologna&Nbsp;
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi (Aouc)
city: Milan
country: Italy
facility: Fondazione Irccs Ca Granda Ospedale Maggiore
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Kagoshima
country: Japan
facility: Kagoshima University Hospital
city: Osaka
country: Japan
facility: Osaka Metropolitan University Hospital
city: Tokyo
country: Japan
facility: Nippon Medical School Hospital
city: TSU
country: Japan
facility: Mie University Hospital
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Hospital Universitari I Politecnic La Fe
city: London
country: United Kingdom
facility: Guys and St Thomas Nhs Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie Nhs Foundation Trust Uk
city: Oxford
country: United Kingdom
facility: University of Oxford
Study officials:
affiliation: Incyte Corporation
name: Incyte Medical Monitor
role: STUDY_DIRECTOR
References: