A Phase 1b/2 Study of FT-2102 in Patients With Advanced Solid Tumors and Gliomas With an IDH1 Mutation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 93
- 试验地点
- 26
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
This Phase 1/2 study will evaluate the safety, efficacy, PK, and PD of FT-2102 as a single agent and in combination with other anti-cancer drugs in patients with advanced solid tumors and gliomas.
The study is divided into two parts: single agent FT-2102 followed by combination therapy.
Part 1: A single agent, open-label study in up to five cohorts (glioma, hepatobiliary tumors, chondrosarcoma, intrahepatic cholangiocarcinoma, and other IDH1 mutant solid tumors) that will include a Phase 1 dose confirmation followed by a Phase 2 investigation of clinical activity in up to 4 cohorts. During the dose confirmation, additional doses or altered dose schedules may be explored.
Part 2: An open-label study of FT-2102 in combination with other anti-cancer agents. Patients will be enrolled across 4 different disease cohorts, examining the effect of FT-2102 + azacitidine (glioma and chondrosarcoma), FT-2102 + nivolumab (hepatobiliary tumors), and FT-2102 + gemcitabine/cisplatin (intrahepatic cholangiocarcinoma). There will be a safety lead-in followed by a Phase 2 evaluation in up to four cohorts of patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Patients must have documented IDH1-R132 gene-mutated disease as evaluated by site
- •Glioma: Advanced glioma that has recurred or progressed following standard therapy, or that has not responded to standard therapy.
- •Hepatobiliary cancer that is relapsed/refractory or intolerant to approved standard-of-care therapy (including: hepatocellular carcinoma, bile duct carcinoma, intrahepatic cholangiocarcinoma or other hepatobiliary carcinomas)
- •Chondrosarcoma that is relapsed or refractory and either locally advanced or metastatic and not amenable to complete surgical excision
- •Intrahepatic cholangiocarcinoma that is advanced nonresectable or metastatic cholangiocarcinoma not eligible for curative resection or transplantation. Phase 1b/Safety Lead-in of Phase 2: relapsed or refractory disease. Combination Phase 2 (beyond Safety Lead-in): have received no more than 1 cycle of gemcitabine/cisplatin therapy
- •Other solid tumors that have relapsed or refractory to standard-of-care therapy with no other available therapeutic options
- •Good performance status
- •Good kidney and liver function
排除标准
- •Prior solid organ or hematopoietic cell transplant
- •Prior treatment with IDH1 inhibitor (single agent cohorts only)
- •Congestive heart failure (New York Heart Association Class III or IV) or unstable angina pectoris. Previous history of myocardial infarction within 1 year prior to study entry, uncontrolled hypertension or uncontrolled arrhythmias
- •Unstable or severe, uncontrolled medical condition (e.g., unstable cardiac function, unstable pulmonary condition, including pneumonitis and/or interstitial lung disease, and uncontrolled diabetes)
- •Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
- •PD-1 only: active autoimmune disease
研究组 & 干预措施
Phase 1b Dose Confirmation Single Agent (Cohorts 1a-5a)
干预措施: FT-2102 (Drug)
Phase 2 Cohorts FT-2102 Single Agent (Cohorts 1a-5a)
干预措施: FT-2102 (Drug)
Phase 1b and 2 Cohorts Combination (Cohorts 1b and 3b)
干预措施: FT-2102 (Drug)
Phase 1b and 2 Cohorts Combination (Cohorts 1b and 3b)
干预措施: Azacitidine (Drug)
Phase 1b and 2 Cohort Combination (Cohort 4b)
干预措施: Gemcitabine and Cisplatin (Drug)
Phase 1b and 2 Cohort Combination (Cohort 2b)
干预措施: FT-2102 (Drug)
Phase 1b and 2 Cohort Combination (Cohort 2b)
干预措施: Nivolumab (Biological)
Phase 1b and 2 Cohort Combination (Cohort 4b)
干预措施: FT-2102 (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: While on treatment
ORR is defined as the proportion of patients who achieved a complete response (CR) or partial response (PR) as per RANO (2010) criteria for patients with high grade glioma (Cohorts 1a and 1b). For patients with low grade glioma, ORR is defined as CR+PR+minor response (MR) as per LGG RANO criteria (2011). For Cohorts 2-5, ORR is defined as CR+PR as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
Number of Participants With a Dose Limiting Toxicity (DLT)
时间窗: Day 1-28
DLTs are AEs unrelated to the underlying disease and considered related to FT-2102. For non-hematologic AEs: Grade 3 or higher per CTCAE v 4.03 criteria except Grade 3 nausea, vomiting, diarrhea, or rash: lasting \<72 hours (with optimal medical management) or clinically relevant Grade 3 or higher non-hematologic laboratory finding. For hematologic AEs: Grade 3 or higher thrombocytopenia or febrile neutropenia or Grade 4 or higher neutropenia lasting for \>7 days.
次要结局
- Time for Half of the Drug to be Absent in Blood Stream Following Dose (T 1/2)(Cycles 1: Day 1 (0, 1, 2, 4, 8 hours post dose), Days 2, 8, 15, 22 pre dose. Cycles 2 Day 1 (0, 1, 2, 4, 8 hours post dose).)
- Apparent Clearance (CL/F)(Cycles 1: Day 1 (0, 1, 2, 4, 8 hours post dose), Days 2, 8, 15, 22 pre dose. Cycles 2 Day 1 (0, 1, 2, 4, 8 hours post dose).)
- Olutasidenib Concentration Within Cerebro-spinal Fluid (CSF)(CSF sample for drug concentration was collected at Day 1 of Cycles 1 and 3 (each cycle is 28 days) and through study completion, up to 24 weeks, on average.)
- Duration of Response (DOR)(From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 44 weeks)
- Peak Plasma Concentration (Cmax)(Cycles 1: Day 1 (0, 1, 2, 4, 8 hours post dose), Days 2, 8, 15, 22 pre dose. Cycles 2 Day 1 (0, 1, 2, 4, 8 hours post dose).)
- Rate of Drug Distribution Within the Blood Stream (Vd/F)(Cycles 1: Day 1 (0, 1, 2, 4, 8 hours post dose), Days 2, 8, 15, 22 pre dose. Cycles 2 Day 1 (0, 1, 2, 4, 8 hours post dose).)
- Progression-Free Survival (PFS)(From time of entry on study through progression, up to 24 weeks, on average)
- Overall Survival (OS)(From date of first dose until the date of death from any cause, assessed up to 101 weeks)
- Time to Response (TTR)(Response may be observed from time of first dose through time of treatment discontinuation, up to 2 years.)
- Area Under the Plasma Concentration Versus Time Curve (AUC)(Cycles 1: Day 1 (0, 1, 2, 4, 8 hours post dose), Days 2, 8, 15, 22 pre dose. Cycles 2 Day 1 (0, 1, 2, 4, 8 hours post dose).)
- Time of Peak Plasma Concentration (Tmax)(Cycles 1: Day 1 (0, 1, 2, 4, 8 hours post dose), Days 2, 8, 15, 22 pre dose. Cycles 2 Day 1 (0, 1, 2, 4, 8 hours post dose).)
- Time to Progression (TTP)(From first dose of study drug through time of disease progression)