A Study to Evaluate INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms

Myeloproliferative Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05936359
• Other study ID #: INCA 33989-101
• Secondary ID: 2022-502514-86-0
• Status: Recruiting
• Phase: Phase 1
• Start date: September 25, 2023
• Est. completion date: February 29, 2028

Study information

• Verified date: May 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, 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 225
• Est. completion date: February 29, 2028
• Est. primary completion date: February 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 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.

Related Conditions & MeSH terms

• Myeloproliferative Disorders
• Myeloproliferative Neoplasms
• Neoplasms

Intervention

Drug:
• INCA033989
INCA033989 will be administered at protocol defined dose.
• Ruxolitinib
Rux will be administered according to Prescribing Information/SmPC.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Royal Brisbane and Women'S Hospital	Herston	Queensland
Australia	Peter Maccallum Cancer Centre	Melbourne	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Canada	Hopital Maisonneuve-Rosemont, Montreal, Qc	Montreal	Quebec
Canada	Princess Margaret Cancer Center	Toronto	Ontario
Denmark	Odense University Hospital	Odense C
Denmark	Sjaellands Universitetshospital	Roskilde
Denmark	Vejle Hospital	Vejle
France	Institut Bergonie	Bordeaux
France	Chu Nimes	Nimes
France	Hospital Saint Louis	Paris
France	Institut Gustave Roussy	Villejuif Cedex
Germany	University Medical Center Rwth Aachen	Aachen
Germany	Universitatsklinikum Halle (Saale)	Halle
Germany	Universitatsklinikum Ulm	ULM
Italy	Azienda Ospedaliero-Universitaria Di Bologna Policlinico S. Orsola - Malpighi	Bologna
Italy	Azienda Ospedaliero-Universitaria Careggi (Aouc)	Firenze
Italy	Fondazione Irccs Ca Granda Ospedale Maggiore	Milan
Japan	National Cancer Center Hospital East	Chiba
Japan	Kagoshima University Hospital	Kagoshima
Japan	Osaka Metropolitan University Hospital	Osaka
Japan	Nippon Medical School Hospital	Tokyo
Japan	Mie University Hospital	TSU
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitari I Politecnic La Fe	Valencia
United Kingdom	Guys and St Thomas Nhs Foundation Trust	London
United Kingdom	The Christie Nhs Foundation Trust Uk	Manchester
United Kingdom	University of Oxford	Oxford

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

Australia,  Canada,  Denmark,  France,  Germany,  Italy,  Japan,  Spain,  United Kingdom, 

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 monotherapy and in combination with ruxolitinib	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 in disease-related allele burden.	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