A Phase 1, Open-Label, Multicenter Study of INCA035784 in Participants With Myeloproliferative Neoplasms (NCT07008118)

This is a Phase 1, multicenter, dose-escalation, and dose-expansion study to investigate the safety, tolerability, PK, PD, and preliminary clinical efficacy of INCA035784 in participants with MPN who are positive for CALR exon-9 mutation. This study will involve Q2W dosing with INCA035784. This IP is a T-cell redirecting bispecific antibody that selectively binds to the N-domain of the surface exposed mCALR and CD3 on T cells, designed to redirect CD3 T cells to recognize and eliminate mCALR-expressing malignant cells.

Trial phase

Phase 1

Trial participation type

This trial has been designed for the Clinical Research of a Drug.

Principal investigator

Prof Andrew Perkins

Key inclusion data

Inclusion: 18 years or older with documented CALR exon-9 mutation and life expectancy of >6 months. MF patients only: Confirmed diagnosis with PMF or post-ET MF per 2022 ICC criteria; Intermediate-2 or high risk DIPSS+ MF according to IWG-MRT criteria; Previous treatment with JAK inhibitors for ? 12 weeks; Myeloblast count of <20% in BM or PB (if BM not evaluable); Evidence of residual burden of disease (Radiologic confirmation of splenomegaly (SV ? 450 mL per MRI or CT) or Palpable spleen of ? 5cm below the left subcostal margin on physical examination at the screening visit). ET patients only: Confirmed diagnosis of ET according to the 2022 ICC criteria; High risk defined as follows: Age > 60 years or older at the time of signing the ICF, or History of thrombosis (arterial or venous) or History of major bleeding (related to the underlying disease) or Bleeding risk, defined as platelet count > 1.5 x 1012/L or platelet count > 1 x 1012/L with documented von Willebrand disease.; Platelet count > 450 x 10*9/L. Exclusion: Presence of any hematologic malignancy other than ET, PMF or post-ET-MF. History of major bleeding or thrombosis event (eg, stroke, deep vein thrombosis, or pulmonary embolism) within the last 3 months prior to study enrollment.