A Study to Evaluate INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms
- 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.
- Short title
- A Study to Evaluate INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms
- Official title
- A Phase 1, Open-Label, Multicenter Study of INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms
- Control arm
- Open label
- Registry reports results
- Listing at source
- Listed
- Recruitment status
- Active, not recruiting
- Phase
- Phase 1
- Study type
- Interventional
- Completion date
- 2028-02-29
- First posted
- 2023-07-07
- Registry last updated
- 2026-08-10
- Primary completion date
- 2028-02-29
- Start date
- 2023-09-25
- Actual participants
- Participants
- Participant count basis
- Actual
- Protocol amendments
- Number of sites
- Registry sponsor category
- Industry
- Lead sponsor
- Incyte Corporation
- Source registry
- ClinicalTrials.gov
- Registry ID
- NCT05936359
- ClinicalTrials.gov ID
- NCT05936359
- Registry record
- Open registry record
- Allocation
- Not randomised
- Model
- Sequential
- Purpose
- Treatment
- Masking
- No masking
Number of participants with Dose Limiting Toxicities (DLTs)
Timeframe: 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)
Timeframe: 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
Timeframe: Up to 3 years and 60 days
Number of participants with TEAEs leading to dose modification or discontinuation.
Participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF
Timeframe: Up to 3 years and 60 days
Defined as the percentage of participants with Response using the revised IWG-MRT and ELN response criteria.
Participants With MF: Percentage of participants achieving spleen volume reduction as defined in the protocol
Timeframe: Up to 3 years and 60 days
Defined as percentage of participants with a protocol defined Spleen Volume Reduction.
Participants with MF with symptomatic anemia: Anemia Response
Timeframe: Up to 3 years and 60 days
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.
Participants With ET: Response Rate
Timeframe: Up to 3 years and 60 days
Defined as the proportion of participants with Complete Response or Partial Response when treated with study drug.
Participants With ET: Mean change from baseline of total symptom score (TSS)
Timeframe: Up to 3 years and 60 days
Mean change of TSS from baseline.
Mean change in disease-related allele burden
Timeframe: Up to 3 years and 60 days
Mean change in disease-related allele burden.
Pharmacokinetics Parameter: Cmax of INCA33989
Timeframe: Up to 3 years and 60 days
Defined as maximum observed plasma concentration of INCA33989.
Pharmacokinetics Parameter: Tmax of INCA033989
Timeframe: Up to 3 years and 60 days
Defined as the time to reach the maximum plasma concentration of INCA33989.
Pharmacokinetics Parameter: Cmin of INCA33989
Timeframe: Up to 3 years and 60 days
Defined as the minimum observed plasma concentration of INCA33989.
Pharmacokinetics Parameter: AUC(0-t) of INCA33989
Timeframe: Up to 3 years and 60 days
Defined as the area under the concentration-time curve up to the last measurable concentration of INCA33989.
Pharmacokinetics Parameter: AUC 0-∞ of INCA33989
Timeframe: Up to 3 years and 60 days
Defined as the area under the concentration-time curve from 0 to infinity of INCA33989.
Pharmacokinetics Parameter: CL/F of INCA33989
Timeframe: Up to 3 years and 60 days
Defined as the apparent oral dose clearance of INCA33989.
Pharmacokinetics Parameter: Vz/F of INCA33989
Timeframe: Up to 3 years and 60 days
Defined as the apparent oral dose volume of distribution of INCA33989.
Pharmacokinetics Parameter: t1/2 of INCA33989
Timeframe: Up to 3 years and 60 days
Defined as the apparent terminal phase disposition half-life of INCA33989.
- Sex
- All
- Age groups
- Adults, Older adults
- Minimum age
- 18 Years
- Healthy volunteers
- No
- 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.
- 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.
- Royal Brisbane and Women'S HospitalHerston, Australia
- Royal Adelaide HospitalAdelaide, Australia
- Peter Maccallum Cancer CentreMelbourne, Australia
- The Alfred HospitalMelbourne, Australia
- Princess Margaret Cancer CenterToronto, Canada
- Hopital Maisonneuve-Rosemont, Montreal, QcMontreal, Canada
- Sjaellands UniversitetshospitalRoskilde, Denmark
- Vejle HospitalVejle, Denmark
- Institut BergonieBordeaux, France
- Chu NimesNîmes, France
- Hospital Saint LouisParis, France
- Institut Gustave RoussyVillejuif, France
- University Medical Center Rwth AachenAachen, Germany
- Universitatsklinikum Halle (Saale)Halle, Germany
- Universitätsklinikum UlmUlm, Germany
- Aou Policlinico S. Orsola-MalpighiBologna, Italy
- Azienda Ospedaliero-Universitaria Careggi (Aouc)Florence, Italy
- Fondazione Irccs Ca Granda Ospedale MaggioreMilan, Italy
- National Cancer Center Hospital EastChiba-ken, Japan
- Kagoshima University HospitalKagoshima, Japan
- Osaka Metropolitan University HospitalOsaka, Japan
- Nippon Medical School HospitalTokyo, Japan
- Mie University HospitalTsu, Japan
- Hospital Universitario 12 de OctubreMadrid, Spain
- Hospital Universitari I Politecnic La FeValencia, Spain
And 3 more, listed on the interactive page.
- Related resource (incyteclinicaltrials.com)
Other registry identifiers
- 2022-502514-86-00
Related records
Drugs (1)
Lead sponsors (1)
Conditions (4)
- Essential thrombocythemia
- Myelodysplastic/myeloproliferative neoplasm
- Myeloproliferative neoplasm Primary condition
- Primary myelofibrosis