Blood and Lymph Conditions

All Conditions

Rare Diseases

Myeloproliferative Disorders

Primary Myelofibrosis

Thrombocytosis

Thrombocythemia, Essential

Bone Marrow Diseases

Hematologic Diseases

Chronic Myeloproliferative Disorders

Essential Thrombocythemia

INCA033989 will be administered at a protocol defined starting regimen in 28-day cycles as monotherapy to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE\[s\]). Participants with myelofibrosis (MF) will enroll in this group.

INCA033989 will be administered at a protocol defined starting regimen in 28-day cycles as monotherapy to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE\[s\]). Participants with with essential thrombocythemia (ET) will enroll in this group.

INCA033989 will be administered at a protocol defined starting regimen in 28- day cycles and will allow for the evaluation of INCA033989 in combination with ruxolitinib to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE\[s\]). Participants with myelofibrosis (MF) exhibiting suboptimal response (SubOpt R) will enroll in this group.

INCA033989 will be administered as monotherapy at the RDE(s) identified during Part 1a. Participants with treatment group A (TGA) myelofibrosis MF will enroll in this group.

INCA033989 will be administered as an add-on therapy in combination with ruxolitinibat at the RDE(s) identified during Part 1a. Participants with treatment Group B (TGB) MF SubOpt R will enroll in this group.

INCA033989 will be administered as monotherapy at the RDE(s) identified during Part 1a. Participants with treatment group A (TGA) essential thrombocythemia (ET) will enroll in this group.

INCA033989 will be administered at the dose level found to exhibit an overall positive benefit/risk as monotherapy or as combination therapy with Ruxolitinib. Participants with myelofibrosis (MF) will enroll in this group. The participants enrolled in the monotherapy arm will be offered the option to crossover to combination therapy with ruxolitinib if a suboptimal response to monotherapy is observed after 12 weeks.

INCA033989 will be administered at protocol defined dose.

INCA033989

Rux will be administered according to Prescribing Information/SmPC.

Ruxolitinib

Incyte Corporation Call Center (US)

Incyte Corporation Call Center (ex-US)

Incyte Medical Monitor

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.

A Study to Evaluate INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With 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

Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.

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.

Defined as the percentage of participants with Response using the revised IWG-MRT and ELN response criteria.

Defined as percentage of participants with a protocol defined Spleen Volume Reduction.

For non transfusion-dependent (TD) participants: An Hb increase relative to baseline as defined in the protocol if non-TD at baseline. For TD participants: Achieving transfusion independency (TI) as defined in the protocol.

Defined as the proportion of participants with Complete Response or Partial Response when treated with study drug.

Mean change in disease-related allele burden.

Defined as maximum observed plasma concentration of INCA33989.

Defined as the time to reach the maximum plasma concentration of INCA33989.

Defined as the minimum observed plasma concentration of INCA33989.

Defined as the area under the concentration-time curve up to the last measurable concentration of INCA33989.

Defined as the area under the concentration-time curve from 0 to infinity of INCA33989.

Defined as the apparent oral dose clearance of INCA33989.

Defined as the apparent oral dose volume of distribution of INCA33989.

Defined as the apparent terminal phase disposition half-life of INCA33989.

Incyte Corporation

Heart and Blood Diseases

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

All Drugs and Chemicals

Vaccines

Monatide (IMS 3015)

200 ug CALRLong36 peptide in water mixed with 500ul montanide

CALRLong36 peptide

Jacob H Grauslund, MD

A phase-I-first in man study in patients with calreticulin(CALR)-mutant MPN by vaccinating with exon 9 mutated peptide with the adjuvant Montanide ISA-51 to monitor safety and toxicity and the immunological response to vaccination.

The Philadelphia-chromosome negative chronic myeloproliferative neoplasms (MPN) are acquired cancer diseases, that arise due to mutations in the hematopoietic stem cells in the bone marrow. Median age at diagnosis is approximately 65 years of age and approximately 400 Danes are diagnosed with MPN annually. The MPN comprise essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). In December 2013 two independent research groups reported on the occurrence of somatic mutations in exon 9 of the calreticulin gene in patients with ET and PMF.

The overall rationale for a vaccine with CALR-mutant epitopes is that it will initiate a CALR-mutant specific immune response, which will "release the brakes" on the CALR-mutant specific immune response.

10 patients treated with standard therapy are needed for the trial and each patient will receive 15 vaccinations over the course of one year.

CALR Exon 9 Mutant Peptide Vaccine to Patients With CALR-mutant Myeloproliferative Neoplasms

A Phase-1-first in Man Study in Patients With CALR-mutant Myeloproliferative Neoplasms by Vaccinating With CALR Exon 9 Mutant Peptide

Next Generation Sequencing pre- and post-treatment

Revised response criteria by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report

Adverse events are graded 1-5 according to the criteria

T-cell cytokine release towards target antigens

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Evaluate INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms	NCT05936359	Myeloproliferat...	INCA033989 Ruxolitinib	18 Years -	Incyte Corporation
CALR Exon 9 Mutant Peptide Vaccine to Patients With CALR-mutant Myeloproliferative Neoplasms	NCT03566446	Myeloproliferat... Essential Throm... Myelofibrosis	CALRLong36 pept...	18 Years -	Herlev Hospital
CALR Exon 9 Mutant Peptide Vaccine to Patients With CALR-mutant Myeloproliferative Neoplasms	NCT03566446	Myeloproliferat... Essential Throm... Myelofibrosis	CALRLong36 pept...	18 Years -	Herlev Hospital
CALR Exon 9 Mutant Peptide Vaccine to Patients With CALR-mutant Myeloproliferative Neoplasms	NCT03566446	Myeloproliferat... Essential Throm... Myelofibrosis	CALRLong36 pept...	18 Years -	Herlev Hospital

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