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

Официальное название

A Phase 1, Open-Label, Multicenter Study of INCA033989 Administered as a Monotherapy or in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasms

Обзор

This study is being conducted to evaluate the safety, tolerability, 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.

Вмешательства

• Препарат INCA033989
  INCA033989 will be administered at protocol defined dose.
• Препарат Ruxolitinib
  Rux will be administered according to Prescribing Information/SmPC.

Первичные конечные точки

• Number of participants with Dose Limiting Toxicities (DLTs) [Срок оценки: Up to 28 days]
• Number of participants with Treatment-emergent Adverse Events (TEAEs) [Срок оценки: Up to 3 years and 60 days]

Вторичные конечные точки (12)

• Participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF [Срок оценки: Up to 3 years and 60 days]
• Participants With MF: Percentage of participants achieving spleen volume reduction as defined in the protocol [Срок оценки: Up to 24 weeks]
• Participants with symptomatic anemia: Anemia Response as defined in the protocol [Срок оценки: Up to 24 weeks]
• Participants with ET: Response using the revised IWG-MRT and ELN response criteria for ET [Срок оценки: Up to 3 years and 60 days]
• Incidence of AEs, ECGs, vital signs, and clinical laboratory evaluation [Срок оценки: Up to 3 years and 60 days]
• Percentage of participants achieving ≥ 50% reduction from baseline in total symptom score (TSS) [Срок оценки: Week 12 and Week 24]
• Mean change from baseline in TSS [Срок оценки: Week 12 and Week 24]
• Mean change in disease-related allele burden [Срок оценки: Up to 3 years and 60 days]
• Pharmacokinetics Parameter: Cmax of INCA033989 alone or for the combination of INCA033989 with ruxolitinib [Срок оценки: Up to 3 years and 60 days]
• Pharmacokinetics Parameter: Tmax of INCA033989 alone or for the combination of INCA033989 with ruxolitinib [Срок оценки: Up to 3 years and 60 days]
• Pharmacokinetics Parameter: Cmin of INCA033989 alone or for the combination of INCA033989 with ruxolitinib [Срок оценки: Up to 3 years and 60 days]
• Pharmacokinetics Parameter: AUC(0-t) of INCA033989 alone or for the combination of INCA033989 with ruxolitinib [Срок оценки: Up to 3 years and 60 days]

Критерии участия

Критерии включения

• 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 or ET as defined in the protocol.

Критерии исключения

• Presence of any hematological malignancy other than ET, PMF, or post-ET MF.
• Prior history of major bleeding, or thrombosis within the last 3 months prior to study enrollment.
• Participants with laboratory values exceeding the protocol defined thresholds.
• Has undergone any prior allogenic or autologous stem-cell transplantation or such transplantation is planned.
• Active invasive malignancy over the previous 2 years.
• History of clinically significant or uncontrolled cardiac disease.
• Active or chronic HBV or active HCV or known history of HIV.
• 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, with the exception of ruxolitinib for TGBs only, within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
• 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.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 13 центров

• City of Hope Medical Center — Duarte
• Stanford Cancer Institute — Palo Alto
• University of Miami Health System — Miami
• The University of Kansas Cancer Center — Westwood
• Johns Hopkins Hospital — Baltimore
• Dana Farber Cancer Institute — Boston
• Washington University School of Medicine — St Louis
• Icahn School of Medicine At Mount Sinai — New York
• … и ещё 5 центров

Идентификаторы

NCT: NCT06034002 · INCA33989-102

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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