A Study to Evaluate INCA035784 in Participants With Myeloproliferative Neoplasms

Official title

A Phase 1, Open-Label, Multicenter Study of INCA035784 in Participants With Myeloproliferative Neoplasms

Overview

This study is being conducted to evaluate the safety and tolerability of INCA035784 in participants with myeloproliferative neoplasms.

Interventions

• Drug 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.

Primary outcome measures

• Number of participants with Dose Limiting Toxicities (DLTs) [Time frame: Up to 28 days]
• Number of participants with Treatment-emergent Adverse Events (TEAEs) [Time frame: Up to approximately 2 years and 90 days]
• Number of participants with TEAEs leading to treatment interruption, discontinuation, or delay [Time frame: Up to approximately 2 years and 90 days]

Secondary outcome measures (12)

• Number of participants with TEAEs leading to dose modification or discontinuation [Time frame: Up to approximately 2 years and 90 days]
• Participants with MF: Response using the revised International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) response criteria for myelofibrosis (MF) [Time frame: Up to approximately 2 years and 90 days]
• Participants with essential thrombocythemia (ET): Response using the revised IWG-MRT and ELN response criteria for ET [Time frame: Up to approximately 2 years and 90 days]
• Participants with symptomatic anemia: Anemia response [Time frame: Up to approximately 2 years and 90 days]
• Participants with spleen volume (SV) ≥ 450 mL at baseline: Percentage of participants achieving spleen volume reduction of ≥ 35% (SVR35) [Time frame: Week 12 and Week 24]
• Participants with SV ≥ 450 mL at baseline: Percentage of participants achieving spleen volume reduction of ≥ 25% (SVR25) [Time frame: Week 12 and Week 24]
• Percentage of participants achieving ≥ 50% reduction from baseline of total symptom score (TSS) [Time frame: Week 12 and Week 24]
• Mean change from baseline in TSS [Time frame: Week 12 and Week 24]
• Pharmacokinetics Parameter (PK): Cmax of INCA035784 [Time frame: Up to approximately 2 years and 90 days]
• Pharmacokinetics Parameter: Tmax of INCA035784 [Time frame: Up to approximately 2 years and 90 days]
• Pharmacokinetics Parameter: Cmin of INCA035784 [Time frame: Up to approximately 2 years and 90 days]
• Pharmacokinetics Parameter: AUC(0-t) of INCA035784 [Time frame: Up to approximately 2 years and 90 days]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 12 centers

• Mayo Clinic Hospital — Phoenix
• Stanford University — Palo Alto
• Colorado Blood Cancer Institute — Denver
• Mayo Clinic-Florida — Jacksonville
• University of Chicago Medical Center — Chicago
• Johns Hopkins University — Baltimore
• Icahn School of Medicine At Mount Sinai — New York
• University of North Carolina At Chapel Hill — Chapel Hill
• … and 4 more centers

Australia · 4 centers

• Macquarie University Hospital — Sydney
• Royal Adelaide Hospital — Adelaide
• The Alfred Hospital — Melbourne
• Linear Clinical Research — Nedlands

Italy · 4 centers

• Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii — Bergamo
• Azienda Ospedaliero Universitaria Careggi-S.O.D. Patologia Medica — Florence
• Fondazione Irccs Ca Granda Ospedale Maggiore — Milan
• Centro Ricerche Cliniche Di Verona — Verona

Belgium · 3 centers

• Cliniques Universitaires Saint-Luc — Brussels
• Universitair Ziekenhuis Gent — Ghent
• Universitaire Ziekenhuizen Leuven — Leuven

Germany · 3 centers

• Universitaetsklinikum Dresden — Dresden
• Universitatsklinikum Halle (Saale) — Halle
• Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii — Mainz

Identifiers

NCT: NCT07008118 · INCA035784-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗