A Phase 1/2, Open-Label, Dose-Escalation/Dose-Expansion, Safety and Tolerability Study of INCB059872 in Subjects With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 116
- 试验地点
- 15
- 主要终点
- Number of Participants Receiving INCB059872 Monotherapy With Any Treatment-emergent Adverse Event (TEAE)
研究概览
简要总结
This is an open-label, dose-escalation/dose-expansion study of INCB059872 in subjects with advanced malignancies. The study will be conducted in 4 parts. Part 1 (mono therapy dose escalation) will determine the recommended dose(s) of INCB059872 for dose expansion, based on maximum tolerated dose and/or a tolerated pharmacologically active dose. Part 2 (dose expansion) will further determine the safety, tolerability, efficacy, PK, and PD of the selected monotherapy dose(s) in AML/MDS, SCLC, myelofibrosis, Ewing sarcoma, and poorly differentiated neuroendocrine tumors. Part 3 will determine the recommended dose(s) of INCB059872 in combination with azacitadine and all-trans retinoic acid in AML and in combination with nivolumab in SCLC. Part 4 will further determine the safety, tolerability, efficacy, PK, and PD of the selected combination dose(s) in Part 3.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects, age 18 years or older.
- •Presence of measurable disease that has been confirmed by histology or cytology.
- •Must not be a candidate for potentially curative therapy or standard-of-care approved therapy
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
排除标准
- •Receipt of anticancer medications, anticancer therapies, or investigational drugs within the defined interval before the first administration of study drug.
- •Any unresolved toxicity ≥ Grade 2 from previous anticancer therapy except for stable chronic toxicities (≤ Grade 2) not expected to resolve.
- •Laboratory and medical history parameters outside Protocol-defined range.
- •Known additional malignancy that is progressing or requires active treatment.
研究组 & 干预措施
INCB059872
干预措施: INCB059872 (Drug)
INCB059872 in combination with other therapies
Initial cohort dose of INCB059872 to evaluate different doses of INCB0599872 in combination with other therapies in the following treatment groups:
- Combination with all-trans retinoic acid (ATRA) in subjects with relapsed/refractory AML.
- Combination with azacitidine in subjects with newly diagnosed, treatment-naive AML
- Combination with nivolumab in subjects with advanced SCLC previously progressed on platinum-based treatment.
Upon identification of the recommended dose(s) for each treatment combination, expansion cohorts of approximately 30 subjects in each treatment group may begin enrollment to further determine safety, tolerability, efficacy, PK, and PD of the selected dose(s).
干预措施: INCB059872 (Drug)
INCB059872 in combination with other therapies
Initial cohort dose of INCB059872 to evaluate different doses of INCB0599872 in combination with other therapies in the following treatment groups:
- Combination with all-trans retinoic acid (ATRA) in subjects with relapsed/refractory AML.
- Combination with azacitidine in subjects with newly diagnosed, treatment-naive AML
- Combination with nivolumab in subjects with advanced SCLC previously progressed on platinum-based treatment.
Upon identification of the recommended dose(s) for each treatment combination, expansion cohorts of approximately 30 subjects in each treatment group may begin enrollment to further determine safety, tolerability, efficacy, PK, and PD of the selected dose(s).
干预措施: all-trans retinoic acid (ATRA) (Drug)
INCB059872 in combination with other therapies
Initial cohort dose of INCB059872 to evaluate different doses of INCB0599872 in combination with other therapies in the following treatment groups:
- Combination with all-trans retinoic acid (ATRA) in subjects with relapsed/refractory AML.
- Combination with azacitidine in subjects with newly diagnosed, treatment-naive AML
- Combination with nivolumab in subjects with advanced SCLC previously progressed on platinum-based treatment.
Upon identification of the recommended dose(s) for each treatment combination, expansion cohorts of approximately 30 subjects in each treatment group may begin enrollment to further determine safety, tolerability, efficacy, PK, and PD of the selected dose(s).
干预措施: azacitidine (Drug)
INCB059872 in combination with other therapies
Initial cohort dose of INCB059872 to evaluate different doses of INCB0599872 in combination with other therapies in the following treatment groups:
- Combination with all-trans retinoic acid (ATRA) in subjects with relapsed/refractory AML.
- Combination with azacitidine in subjects with newly diagnosed, treatment-naive AML
- Combination with nivolumab in subjects with advanced SCLC previously progressed on platinum-based treatment.
Upon identification of the recommended dose(s) for each treatment combination, expansion cohorts of approximately 30 subjects in each treatment group may begin enrollment to further determine safety, tolerability, efficacy, PK, and PD of the selected dose(s).
干预措施: nivolumab (Drug)
结局指标
主要结局
Number of Participants Receiving INCB059872 Monotherapy With Any Treatment-emergent Adverse Event (TEAE)
时间窗: up to 588 days
Adverse events (AEs) were defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). TEAEs were defined as AEs either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug.
Number of Participants Receiving INCB059872 Combination Therapy With Any TEAE
时间窗: up to 1387 days
AEs were defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). TEAEs were defined as AEs either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug.
次要结局
- Objective Response Rate (ORR) in Participants With the Indicated Type of Solid Tumors Who Received INCB059872 Monotherapy(up to 518 days)
- ORR for Altering the Natural History of the Disease in Participants With Acute Myeloid Leukemia (AML) Who Received INCB059872 Monotherapy(up to 85 days)
- ORR for Altering the Natural History of the Disease in Participants With Myelodysplastic Syndrome (MDS) Who Received INCB059872 Monotherapy(up to 61 days)
- Change From Baseline in Spleen Volume Reduction (SVR) at Week 12 in Participants With Myelofibrosis (MF) Who Received INCB059872 Monotherapy(Baseline; Week 12)
- Cmax of INCB059872 in Plasma When Received as Monotherapy(Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose)
- Tmax of INCB059872 in Plasma When Received as Monotherapy(Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose)
- AUC(0-τ) of INCB059872 in Plasma When Received as Monotherapy(Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose)
- t1/2 of INCB059872 in Plasma When Received as Monotherapy(Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose)
- ORR in Participants With SCLC Who Received Combination Therapy(up to 1353 days)
- CL/F of INCB059872 in Plasma When Received as Monotherapy(Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose)
- ORR for Altering the Natural History of the Disease in Participants With AML Who Received Combination Therapy(up to 208 days)
- ORR for Altering the Natural History of the Disease in Participants With MDS Who Received Combination Therapy(up to 85 days)
- Cmax of INCB059872 in Plasma When Received as Combination Therapy(Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose)
- AUC(0-τ) of INCB059872 in Plasma When Received as Combination Therapy(Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose)
- t1/2 of INCB059872 in Plasma When Received as Combination Therapy(Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose)
- CL/F of INCB059872 in Plasma When Received as Combination Therapy(Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose)
- Tmax of INCB059872 in Plasma When Received as Combination Therapy(Cycle 1 Day 15: 0.5, 1, 2, 4, and 6 hours after INCB059872 dose)