A Phase 1, Dose-Escalation and Expansion Trial of PT2977, a HIF-2α Inhibitor, in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 120
- 主要终点
- maximum tolerated dose (MTD)
研究概览
简要总结
The primary objective of this study is to identify the maximum tolerated dose (MTD) of belzutifan Tablets and/or the recommended Phase 2 dose (RP2D) of belzutifan Tablets in patients with advanced solid tumors
详细描述
Part 1A: This is a Phase 1, multiple-dose, dose-escalation trial of belzutifan Tablets, where patients with advanced solid tumors will be assigned to sequential dose cohorts. Patient safety will be monitored with frequent physical examinations, vital sign measurements, electrocardiograms (ECGs), and hematology and chemistry laboratory studies, and by recording all adverse events (AEs). Blood will be obtained for analysis of the concentration of belzutifan and to assess biomarkers.
Part 1B: Once the MTD and/or the RP2D is achieved, and expansion cohort of 50 patients with advanced clear cell renal cell carcinoma (ccRCC) will be enrolled.
Part 2: After determination of the MTD/RP2D, up to 25 patients with other specified solid tumors may be enrolled. Up to 3 different tumor types may be included in this part of the study.
Part 2A: A cohort of 25 patients with glioblastoma (GBM)
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
- •Has a diagnosis of locally advanced or metastatic solid tumor
- •Is of age ≥ 18 years
- •Has a life expectancy of ≥ 6 months
- •Has adequate organ function
- •If a female patient, must not be pregnant or breastfeeding and not a woman of childbearing potential (WOCBP) OR a WOCBP who uses contraception or is abstinent from heterosexual intercourse during the study and for a minimum of 30 days after the last study drug administration, or if a male patient, must be abstinent from heterosexual intercourse OR agree to use contraception
- •Able to swallow oral medications
- •Additional Inclusion Criteria for GBM cohort
- •Must have histologically confirmed glioblastoma, IDH-wild type that is first recurrent following radiation therapy and temozolomide according to the Response Assessment in Neuro-Oncology (RANO) criteria
- •Must have archival tumor tissue available from a previous surgery for glioblastoma
- •Must have measurable (defined as at least 1 cm x 1 cm) contrast-enhancing lesion by MRI imaging within 21 days of starting treatment
- •Must be able to undergo MRI of the brain with gadolinium. Patients must be maintained on a stable or decreasing dose of corticosteroid regimen (no increase for 5 days) prior to this baseline MRI
- •Must have recovered from prior therapy to grade ≤1 severity (except for alopecia and lymphocytopenia) National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)
排除标准
- •Has a history of untreated brain metastasis or history of leptomeningeal disease or spinal cord compression
- •Has failed to recover from the reversible effects of prior anticancer therapy (does not apply to GBM cohort)
- •Has uncontrolled or poorly controlled hypertension
- •Has malabsorption due to prior gastrointestinal (GI) surgery or GI disease
- •Has had any major cardiovascular event within 6 months prior to study drug administration
- •Has any other clinically significant cardiac, respiratory, or other medical or psychiatric condition that might interfere with participation in the trial or interfere with the interpretation of trial results
- •Has had major surgery within 4 weeks before first study drug administration
- •Has known HIV
- •Has an active infection requiring systemic treatment
- •Is participating in another therapeutic clinical trial
- •Additional Excusion Criteria for GBM cohort:
- •Has received prior anti-VEGF therapy including bevacizumab (i.e. patients must be bevacizumab naïve)
- •Is receiving enzyme-inducing anti-epileptic drugs (EIAED). Patients may be on non-enzyme inducing anti-epileptic drugs or not be taking any anti-epileptic drugs. Patients previously treated with EIAED may be enrolled if they have been off the EIAED for 10 days or more prior to the first dose of belzutifan
研究组 & 干预措施
Part 2
Drug: Part 2: Belzutifan for the treatment of other specified solid tumors
Belzutifan inhibits HIF-2α and is a novel approach to treatment of specified solid tumors.
干预措施: Belzutifan (Drug)
Part 1A
Drug: PART 1A: Belzutifan for the treatment of advanced solid tumors
Belzutifan inhibits HIF-2α and is a novel approach to treatment of solid tumors.
干预措施: Belzutifan (Drug)
Part 1B
Drug: PART 1B: Belzutifan for the treatment of advanced ccRCC
Belzutifan inhibits HIF-2α and is a novel approach to treatment of ccRCC.
干预措施: Belzutifan (Drug)
Part 2A
Drug: Part 2A: Belzutifan for the treatment of patients with recurrent GBM who have been previously treated with radiation therapy and temozolomide
Belzutifan inhibits HIF-2α and is a novel approach to treatment of specified solid tumors.
干预措施: Belzutifan (Drug)
结局指标
主要结局
maximum tolerated dose (MTD)
时间窗: 3 Weeks
21-Day Dose Limiting Toxicity Observation Period per Dose Group
次要结局
未报告次要终点