Evaluating INCA033989 for 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

This study is testing a new drug called INCA033989 to see how safe it is and how well it works for people with myeloproliferative neoplasms, both on its own and with another medication.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 225 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Incyte Corporation (industry)
• Drugs / interventions: chemotherapy, ruxolitinib
• Locations: 29 sites (Herston, Queensland and 28 other locations)
• Trial ID: NCT05936359 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and tolerability of INCA033989, both alone and in combination with ruxolitinib, in patients with myeloproliferative neoplasms. It aims to determine the maximum tolerated dose and recommended dose for expansion through monitoring dose-limiting toxicity. Participants will undergo regular bone marrow biopsies and aspirates to assess treatment effects. The study focuses on patients with specific mutations and conditions related to myeloproliferative neoplasms.

Who should consider this trial

Good fit: Ideal candidates include individuals with myeloproliferative neoplasms who have a documented CALR mutation and a life expectancy of more than 6 months.

Not a fit: Patients with other hematological malignancies or those with active invasive malignancies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with myeloproliferative neoplasms.

How similar studies have performed: Other studies have shown promise with similar approaches, but this specific combination is being evaluated for the first time.

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.

Where this trial is running

Herston, Queensland and 28 other locations

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• Odense University Hospital — Odense C, Denmark (WITHDRAWN)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

Study contacts

• Study coordinator: Incyte Corporation Call Center (US)

Conditions: Myeloproliferative Neoplasms, Ruxolitinib, Myelofibrosis, Essential thrombocythemia, CALR mutation