RecruitingPhase 1NCT05936359

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

A Phase 1, Open-Label, Multicenter Study of INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms


Sponsor

Incyte Corporation

Enrollment

225 participants

Start Date

Sep 25, 2023

Study Type

INTERVENTIONAL

Conditions

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

Min Age: 18 Years

Inclusion Criteria4

  • 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 Criteria10

  • 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.

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Interventions

DRUGINCA033989

INCA033989 will be administered at protocol defined dose.

DRUGRuxolitinib

Rux will be administered according to Prescribing Information/SmPC.


Locations(29)

Royal Brisbane and Women'S Hospital

Herston, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Peter Maccallum Cancer Centre

Melbourne, Victoria, Australia

The Alfred Hospital

Melbourne, Victoria, Australia

Princess Margaret Cancer Center

Toronto, Ontario, Canada

Hopital Maisonneuve-Rosemont, Montreal, Qc

Montreal, Quebec, Canada

Odense University Hospital

Odense C, Denmark

Sjaellands Universitetshospital

Roskilde, Denmark

Vejle Hospital

Vejle, Denmark

Institut Bergonie

Bordeaux, France

Chu Nimes

Nîmes, France

Hospital Saint Louis

Paris, France

Institut Gustave Roussy

Villejuif, France

University Medical Center Rwth Aachen

Aachen, Germany

Universitatsklinikum Halle (Saale)

Halle, Germany

Universitätsklinikum Ulm

Ulm, Germany

Aou Policlinico S. Orsola-Malpighi

Bologna, Italy

Azienda Ospedaliero-Universitaria Careggi (Aouc)

Florence, Italy

Fondazione Irccs Ca Granda Ospedale Maggiore

Milan, Italy

National Cancer Center Hospital East

Chiba-ken, Japan

Kagoshima University Hospital

Kagoshima, Japan

Osaka Metropolitan University Hospital

Osaka, Japan

Nippon Medical School Hospital

Tokyo, Japan

Mie University Hospital

Tsu, Japan

Hospital Universitario 12 de Octubre

Madrid, Spain

Hospital Universitari I Politecnic La Fe

Valencia, Spain

Guys and St Thomas Nhs Foundation Trust

London, United Kingdom

The Christie Nhs Foundation Trust Uk

Manchester, United Kingdom

University of Oxford

Oxford, United Kingdom

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NCT05936359


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