INCA033989: INCA033989 will be administered at protocol defined dose.
Ruxolitinib: Rux will be administered according to Prescribing Information/SmPC.
Study 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
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
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 3 years and 60 days Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug monotherapy and in combination with ruxolitinib
Number of participants with TEAEs leading to dose modification or discontinuation — Up to 3 years and 60 days Number of participants with TEAEs leading to dose modification or discontinuation.
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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