INCA035784: INCA035784 will be administered at the assigned dose in the dose escalation part and at the protocol defined dose in the dose expansion part.
Study summary
This study is being conducted to evaluate the safety and tolerability of INCA035784 in participants with myeloproliferative neoplasms.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Age 18 years or older at the time of signing the ICF
* ECOG performance status of 0 to 1 for the dose escalation (Part 1a) and 0 to 2 for the dose expansion (Part 1b)
* Documented CALR exon-9 mutation
* Confirmed diagnosis of MPN according to the 2022 ICC criteria:
* DIPSS+ intermediate-2/high-risk MF with prior JAKi, \<20% blasts, and measurable spleen
* High-risk ET with platelets \>450×10⁹/L
* Resistant, refractory, intolerant, or has lost response to ≥1 prior line of therapy for MF and ≥2 prior lines for ET (unless only a single standard-of-care option is approved in the participating country)
* No prior stem cell transplant and none planned within 6 months
* Minimum Laboratory Requirements:
* Platelet count ≥50 × 10⁹/L
* Absolute neutrophil count ≥1 × 10⁹/L
* International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤1.5 × upper limit of normal (ULN), unless receiving vitamin K antagonists
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<2.5 × ULN
* Total bilirubin \<2 × ULN
* Estimated creatinine clearance \>45 or \>30 mL/min (depending on study part)
Exclusion Criteria:
* Major bleeding or thrombosis (e.g., stroke, DVT, PE) within the past 3 months
* Active or high-risk HBV, HCV, or HIV infection, or other chronic active infections requiring systemic treatment
* Active invasive cancer within the past 2 years, except certain early-stage or low-risk cancers (e.g., resected skin, cervical, thyroid, or prostate cancer)
* Pregnant or unwilling to avoid pregnancy or fathering a child during the study and for a defined period after the last dose.
Other protocol-defined Inclusion/Exclusion Criteria may apply.
Primary outcome measure(s)
Number of participants with Dose Limiting Toxicities (DLTs) — Up to 28 days Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.
Number of participants with Treatment-emergent Adverse Events (TEAEs) — Up to approximately 2 years and 90 days Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug up to 90 days after the last dose of study drug.
Number of participants with TEAEs leading to treatment interruption, discontinuation, or delay — Up to approximately 2 years and 90 days Number of participants with TEAEs leading to treatment interruption, discontinuation, or delay.
Trial sites (26)
Facility
City
Region
Status
Mayo Clinic Hospital
Phoenix
Arizona
Recruiting
Stanford University
Palo Alto
California
Recruiting
Colorado Blood Cancer Institute
Denver
Colorado
Recruiting
Mayo Clinic-Florida
Jacksonville
Florida
Recruiting
University of Chicago Medical Center
Chicago
Illinois
Recruiting
Johns Hopkins University
Baltimore
Maryland
Recruiting
Icahn School of Medicine At Mount Sinai
New York
New York
Recruiting
University of North Carolina At Chapel Hill
Chapel Hill
North Carolina
Recruiting
South Austin Medical Center
Austin
Texas
Recruiting
University of Texas Southwestern Medical Center Harold C Simmons Comprehensive Cancer Center Blood
Dallas
Texas
Recruiting
Huntsman Cancer Institute At University of Utah
Salt Lake City
Utah
Recruiting
Medical College of Wisconsin
Milwaukee
Wisconsin
Recruiting
Macquarie University Hospital
Sydney
New South Wales
Recruiting
Royal Adelaide Hospital
Adelaide
South Australia
Recruiting
The Alfred Hospital
Melbourne
Victoria
Recruiting
Linear Clinical Research
Nedlands
Western Australia
Recruiting
Cliniques Universitaires Saint-Luc
Brussels
Belgium
Not Yet Recruiting
Universitair Ziekenhuis Gent
Ghent
Belgium
Not Yet Recruiting
Universitaire Ziekenhuizen Leuven
Leuven
Belgium
Not Yet Recruiting
Universitaetsklinikum Dresden
Dresden
Germany
Not Yet Recruiting
Universitatsklinikum Halle (Saale)
Halle
Germany
Not Yet Recruiting
Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii
Mainz
Germany
Not Yet Recruiting
Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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