A Phase 1 Study of BOS172738 in Patients With Advanced Solid Tumors With RET Gene Alterations Including Non-Small Cell Lung Cancer (NSCLC) and Medullary Thyroid Cancer (MTC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 117
- 试验地点
- 21
- 主要终点
- Number of participants with any non-serious TEAE
研究概览
简要总结
This study will be conducted to assess the safety and tolerability of BOS172738 when administered to patients with advanced solid tumors with rearranged during transfection (RET) gene alterations and also to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of BOS172738.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Participants are eligible to be included in the study only if all of the following criteria apply:
- •Male or female participants must be ≥ 18 years, at the time of signing the informed consent
- •Diagnosis of advanced solid tumor with a documented rearranged during transfection (RET) gene altered malignancy as determined locally by a DNA based assay of tumor tissue and/or blood
- •Participants must have no alternative approved therapy.
- •For participants in Part B expansion cohort only: documented local diagnosis of either 1) advanced RET gene fusion non-small cell lung cancer (NSCLC); 2) advanced RET gene mutant medullary thyroid cancer (MTC); or 3) other RET gene altered advanced tumors or NSCLC/MTC with prior specific RET gene targeted therapy
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Negative pregnancy test for females of child bearing potential; must be surgically sterile, postmenopausal, or willing and able to be compliant with a contraceptive regimen
- •Contraceptive use by men or women should be consistent with local regulations.
- •Capable of giving signed informed consent
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Inability to take oral medications or gastrointestinal (GI) conditions that can interfere with the swallowing or absorption of study medication
- •Uncontrolled or severe concurrent medical condition
- •History of upper GI bleeding, ulceration, or perforation within 12 months prior to the first dose of study drug
- •Known history of stroke or cerebrovascular accident within 6 months prior to the first dose of study drug
- •Participants with known infection with human immunodeficiency virus (HIV) or Acquired Immune Deficiency Syndrome (AIDS) (testing not required)
- •Participants who are hepatitis B surface antigen positive or participants who are hepatitis C antibody positive (Participants who have been successfully treated for hepatitis C virus [HCV] are eligible if an undetectable HCV viral load at least 6 months after completion of treatment can be demonstrated.)
- •Any evidence of serious active infections
- •Uncontrolled or severe cardiovascular disease
- •Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements
- •Participants with a prior or concurrent malignancy other than the malignancies under study
- •Ongoing cancer directed therapy
研究组 & 干预措施
BOS172738
In Part A (dose escalation), participants with advanced solid tumors with rearranged during transfection (RET) gene alterations will receive oral BOS172738 at a starting dose of 10 milligrams (mg) once daily in each 28-day cycle. In Part B (dose expansion), participants with RET gene-fusion non-small cell lung cancer (NSCLC), with RET gene-mutant medullary thyroid cancer (MTC), and with RET gene-altered advanced tumors or NSCLC/MTC with prior specific RET gene-targeted therapy will be enrolled in Cohorts 1, 2, and 3, respectively, and will receive oral BOS172738 once daily in each 28-day cycle at the recommended Phase 2 dose (RP2D) established in Part A.
干预措施: BOS172738 (Drug)
结局指标
主要结局
Number of participants with any non-serious TEAE
时间窗: a minimum of approximately 3 months
Number of participants with grade 3, grade 4, or grade 5 TEAEs
时间窗: a minimum of approximately 3 months
Number of participants with any related TEAE
时间窗: a minimum of approximately 3 months
Number of participants with any treatment-emergent (TE) serious adverse event (SAE)
时间窗: a minimum of approximately 3 months
Number of participants with any TEAE leading to study drug discontinuation
时间窗: a minimum of approximately 3 months
Maximum tolerated dose (MTD) of BOS172738
时间窗: throughout Cycle 1 (each cycle is 28 days)
Recommended phase 2 dose (RP2D) of BOS172738
时间窗: 28-day cycles in Part A (minimum of one dose of BOS172738 received)
次要结局
- Objective Disease Control Rate (ODCR)(a minimum of approximately 3 months)
- Duration of Response (DoR)(a minimum of approximately 3 months)
- Time to Response (TTR)(a minimum of approximately 3 months)
- Duration of Complete Response (DoCR)(a minimum of approximately 3 months)
- Objective Response Rate (ORR)(a minimum of approximately 3 months)
- Progression-Free Survival (PFS)(a minimum of approximately 3 months)
- Part A: Plasma concentration of BOS172738(Pre-dose on Days 1, 2, 15, and 16 of Cycle 1; Day 1 of Cycles 2, 3, and 4. 15 minutes (min); 30 min; 1, 3, 6, 8, 10, and 12 hours after the BOS1722722 dose on Days 1 and 15 of Cycle 1 (each cycle is 28 days))
- Part B: Plasma concentration of BOS172738(Pre-dose on Day 1 of Cycles 2, 3, and 4 (each cycle is 28 days))