A PHASE I DOSE ESCALATION AND EXPANDED COHORT STUDY OF PF 06821497 (MEVROMETOSTAT) IN THE TREATMENT OF ADULT PATIENTS WITH RELAPSED/REFRACTORY SMALL CELL LUNG CANCER (SCLC), CASTRATION RESISTANT PROSTATE CANCER (CRPC) AND FOLLICULAR LYMPHOMA (FL)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Pfizer
- 入组人数
- 453
- 试验地点
- 154
- 主要终点
- Overall safety profile including adverse events
研究概览
简要总结
The purpose of this study is to learn about the safety and effects of the study medicine (called Mevrometostat) for the possible treatment of Relapsed/ Refractory Small Cell Lung Cancer (SCLC), Castration Resistant Prostate Cancer (CRPC) and Follicular Lymphoma (FL). The study consists of 3 parts; Part 1 and 2 enrolled participants with SCLC, metastatic CRPC, and FL are closed for enrollment.
Part 3, which is open for enrollment is seeking men who:
- have Castration Resistant Prostate Cancer (CRPC) and
- have previously received treatment for CRPC and have progressed from the last treatment
All participants in Part 3 of this study will receive mevrometostat and/ or enzalutamide. Part 3 consists of 2 sub studies each has an assessment phase and a maintenance phase. The Part 3 DDI substudy consist of 2 cohorts, Cohort 1 (monotherapy cohort) and Cohort 2 (Combination cohort).
In the assessment phase:
- participants in the BE substudy will take 3 single doses of mevrometostat by mouth over 3 periods.
- participants in the DDI substudy Cohort 1 (monotherapy cohort) will take mevrometostat 2 times a day and/or itraconazole 1 time a day based on a present schedule.
- participants in the DDI substudy Cohort 2 (combination cohort) will take mevrometostat 2 times a day, enzalutamide 1 time a day, and/or itraconazole 1 time a day based on a present schedule.
After completion of the assessment phase, participants will enter the maintenance phase where they will receive mevrometostat 2 times a day and enzalutamide 1 time a day by mouth until their cancer is no longer responding.
The study will look at the experiences of participanrs receiving the study medicine. This will help see if the study medicine is safe and effective.
详细描述
This is an open label, multi center, Phase 1 dose escalation and dose expansion study of mevrometostat (PF-06821497) administered orally BID as a single agent or in combination with SOC to patients with CRPC, SCLC, and FL. The study consists of three parts (Part 1, Part 2, and Part 3) along with the Japan and China monotherapy cohorts. Part 1 and Part 2 are closed for enrollment. Part 1 tested monotherapy in 3 cohorts (Parts 1A, 1B, and 1C); Part 2 tested combination therapy in Parts 2A (dose escalation), 2B and 2C (does expansion).
Part 3 consists of the Bioequivalence (BE) and drug-drug interaction (DDI) substudies and are open for enrollment. The BE substudy will test between 2 mevrometostat formulation to confirm that they work in the body the same way. The DDI substudy will evaluate the effect of a strong CYP3A4 (an enzyme in your body that breaks down/ removes drugs) inhibitor on the PK of mevrometostat; a strong CYP3A4 inhibitor may slow down the breakdown/ removal of drugs in your body. The Sponsor may choose to delay or discontinue any cohorts or substudies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Part 1 and Part 2 (Closed for enrollment).
- •Part 3 Key Inclusion Criteria:
- •Histological or cytological diagnosis of castration resistant prostate cancer.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-2 with expected life expectancy of at least 6 months.
- •Adequate bone marrow, renal, and liver function
排除标准
- •Prior irradiation to >25% of the bone marrow.
- •QTcF interval >480 msec at screening.
- •Hypertension that cannot be controlled by medications (>150/90 mmHg despite optimal medical therapy).
- •Known or suspected hypersensitivity to PF 06821497 or any components or enzalutamide (CRPC)
- •Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery.
- •Current use or anticipated need for food or drugs that are known strong and moderate CYP3A4/5 inducers or inhibitors
- •Prior enzalutamide within the last 4 weeks
- •DDI SUBSTUDY:
- •history of CHF or evidence of ventricular dysfunction
- •fructose intolerance
- •coadministration of CYP3A4 substrates
研究组 & 干预措施
Dose Escalation (Part 2A)
Participants with mCRPC and SCLC will receive mevrometostat at escalating dose levels in combination with SOC.
干预措施: Mervometostat (PF-06821497) (Drug)
DDI Substudy
The DDI substudy assessment phase will consist of 2 Cohorts, Cohort 1 (monotherapy cohort) and Cohort 2 (combination cohort). In the Cohort 1 assessment phase, each enrolled participant will receive a combination of mevrometostat and itraconazole based on preset schedule. In the Cohort 2 assessment phase, each enrolled participant will receive a combination of mevrometostat, enzalutamide, and itraconazole based on preset schedule. In the maintenance phase, each participant will receive mevrometostat 2 times a day and enzalutamide 1 time a day.
干预措施: Enzalutamide (Drug)
Dose Escalation (Part 1A)
Participants with SCLC, CRPC and FL will receive mevrometostat at escalating dose levels
干预措施: Mervometostat (PF-06821497) (Drug)
Dose Escalation (Part 1C)
Participants with mCRPC will receive mevrometostat at escalating dose levels.
干预措施: Mervometostat (PF-06821497) (Drug)
Dose Escalation (Part 1B)
Participants with FL will receive mevrometostat at escalating dose levels
干预措施: Mervometostat (PF-06821497) (Drug)
China cohort
Participants will receive mevrometostat at one or two doses
干预措施: Mervometostat (PF-06821497) (Drug)
DDI Substudy
The DDI substudy assessment phase will consist of 2 Cohorts, Cohort 1 (monotherapy cohort) and Cohort 2 (combination cohort). In the Cohort 1 assessment phase, each enrolled participant will receive a combination of mevrometostat and itraconazole based on preset schedule. In the Cohort 2 assessment phase, each enrolled participant will receive a combination of mevrometostat, enzalutamide, and itraconazole based on preset schedule. In the maintenance phase, each participant will receive mevrometostat 2 times a day and enzalutamide 1 time a day.
干预措施: Itraconazole (Drug)
Dose Expansion (Part 2C)
Participants with mCRPC will receive mevrometostat at a different dose/dosing regimen than that of Part 2B in combination with SOC
干预措施: Mervometostat (PF-06821497) (Drug)
Dose Expansion (Part 2C)
Participants with mCRPC will receive mevrometostat at a different dose/dosing regimen than that of Part 2B in combination with SOC
干预措施: Enzalutamide (Drug)
Dose Expansion (Part 2B)
Participants with CRPC will receive mevrometostat in combination with SOC or SOC alone.
干预措施: Enzalutamide (Drug)
Dose Escalation (Part 2A)
Participants with mCRPC and SCLC will receive mevrometostat at escalating dose levels in combination with SOC.
干预措施: Enzalutamide (Drug)
BE Substudy
In the assessment phase, each enrolled participant will receive single doses of the 2 different mevrometostat formulations in 3 periods with alternating dosing and washout between each dose. In the maintenance phase, each participant will receive mevrometostat 2 times a day and enzalutamide 1 time a day.
干预措施: Enzalutamide (Drug)
BE Substudy
In the assessment phase, each enrolled participant will receive single doses of the 2 different mevrometostat formulations in 3 periods with alternating dosing and washout between each dose. In the maintenance phase, each participant will receive mevrometostat 2 times a day and enzalutamide 1 time a day.
干预措施: Mervometostat (PF-06821497) (Drug)
DDI Substudy
The DDI substudy assessment phase will consist of 2 Cohorts, Cohort 1 (monotherapy cohort) and Cohort 2 (combination cohort). In the Cohort 1 assessment phase, each enrolled participant will receive a combination of mevrometostat and itraconazole based on preset schedule. In the Cohort 2 assessment phase, each enrolled participant will receive a combination of mevrometostat, enzalutamide, and itraconazole based on preset schedule. In the maintenance phase, each participant will receive mevrometostat 2 times a day and enzalutamide 1 time a day.
干预措施: Mervometostat (PF-06821497) (Drug)
Dose Expansion (Part 2B)
Participants with CRPC will receive mevrometostat in combination with SOC or SOC alone.
干预措施: Mervometostat (PF-06821497) (Drug)
Japan Cohort
Participants with CRPC will receive mevrometostat at one or two doses
干预措施: Mervometostat (PF-06821497) (Drug)
结局指标
主要结局
Overall safety profile including adverse events
时间窗: Baseline up to approximately 2 years
Adverse Events will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version \[4.03\])
Percentage of patients with dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD)
时间窗: Baseline up to 90 days
First cycle DLTs will be utilized to determine the MTD
Overall safety profile including vital signs
时间窗: Baseline up to approximately 2 years
Vital sign changes from baseline including blood pressure, heart rate, ECG changes.
Preliminary efficacy determination as evaluated by disease specific response criteria
时间窗: Through study completion, approximately 2 years past last patient first visit.
Objective response using Response Evaluation Criteria in Lymphoma (RECIL) for lymphoma, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for solid tumors including Small Cell Lung Cancer (SCLC) and Prostate Cancer Working Group 3 (PCWG3) for Castration Resistant Prostate Cancer (CRPC). Progression-free survival in Part 2B in patients with CRPC.
Overall safety profile including laboratory abnormalities
时间窗: Baseline up to approximately 2 years
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version \[4.03\]), and timing.
Evaluate time to event mevrometostat and enzalutamide vs enzalutamide alone including radiographic prgression free survival
时间窗: Baseline until disease progression or death or through study completion (approx 2 years)
PCWG3
次要结局
- Evaluate time to event anti-tumor activity of mevrometostat including progression-free survival (PFS), PSA50, Duration of Response (DoR), Time to first skeletal related event and Time to symptomatic skeletal related event, depending on tumor type.(Baseline and every 21 days through time of confirmed disease progression, unacceptable toxicity, or through study completion, approximately 2 years.)
- Pharmacokinetic Parameters: Time to Reach Maximum Observed Plasma Concentration (Tmax)(At specific timepoints from Cycle 1 day 1 to End of Treatment visit)
- Pharmacokinetic Parameters: Apparent Volume of Distribution (Vz/F)(At specific timepoints from Cycle 1 day 1 to End of Treatment visit)
- Pharmacokinetic Parameters: Plasma Decay Half-Life (t1/2)(At specific timepoints from Cycle 1 day 1 to End of Treatment visit)
- Evaluate the impact of mevrometostat on patient reported outcomes.(At specific time-points from Cycle 1 Day 1 to End of Treatment visit.)
- Pharmacokinetic Parameters: Area Under the Curve (AUC)(At specific timepoints from Cycle 1 day 1 to End of Treatment visit)
- Evaluate overall survival(Baseline up to approximately 2 years)
- Pharmacokinetic Parameters: Apparent Oral Clearance (CL/F)(At specific timepoints from Cycle 1 day 1 to End of Treatment visit)
- Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax)(At specific timepoints from Cycle 1 day 1 to End of Treatment visit)
- Impact of mevrometostat in combination with enzalutamide, enzalutamide alone and mevrometostat alone on symptoms and symptomatic toxicity(At specific time points from Cycle1 Day 1 to end of treatment)