A Phase 1/2 Study of PBI-200 in Subjects With NTRK-Fusion-Positive Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 29
- 试验地点
- 42
- 主要终点
- Phase 1: Recommended Phase 2 Dose
研究概览
简要总结
This is a first-in-human, open-label, multicenter, dose-escalation, safety, PK, and biomarker study of PBI-200 in subjects with NTRK-fusion-positive advanced or metastatic solid tumors.
详细描述
This is a first-in-human, open-label, multicenter, dose-escalation, safety, PK, and biomarker study of PBI-200 in subjects with NTRK-fusion-positive advanced or metastatic solid tumors. Phase 1 will also include subjects with NTRK-amplified advanced or metastatic solid tumors or refractory EWSR1-WT1-fusion-positive desmoplastic small round cell tumors (DSRCTs).
Phase 1 is the dose-escalation portion of the study in which the evaluation of safety and tolerability and establishing the RP2D are primary objectives. Once the RP2D has been established, two expansion cohorts will open to accrual, a Non-Brain Primary Tumor cohort and a Primary Brian Tumor cohort.
Although this was intended to be a Phase 1/2 trial, the trial was terminated without proceeding to Phase 2.
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
- •Subject has one of the following solid tumors which has progressed on or following at least one systemic therapy regimen administered for advanced or metastatic disease or for which no approved therapy exists:
- •NTRK-fusion-positive, locally advanced (i.e., not amenable to surgical resection) or metastatic solid tumor Note: Subjects with any grade of malignant glioma previously treated with systemic therapy are eligible.
- •NTRK-gene amplified, locally advanced or metastatic solid tumor
- •EWSR1-WT1-positive DSRCTs.
- •Subjects with NTRK-fusion-positive solid tumors other than primary brain tumors must have previously received treatment with a TRK inhibitor, unless the subject does not have access to TRK-inhibitor therapy (e.g., no TRK inhibitor is marketed and available to the subject in the subject's country) or the subject has declined treatment with available marketed TRK inhibitors.
- •Subjects with NTRK-gene amplified solid tumors, primary brain tumors or EWSR1-WT1-positive DSRCTs may have received prior treatment with a TRK inhibitor but this is not required.
- •Has measurable disease by RECIST v1.1 for subjects with non-brain primary tumors or RANO criteria for subjects with primary brain tumors.
- •Subjects with non-brain primary tumors must have previously received treatment with a TRK inhibitor and a documented resistance mutation(s) (e.g., solvent front, gatekeeper or xDFG mutation). Archival tissue from a prior biopsy taken after the subject completed TRK inhibitor treatment but prior to additional systemic therapy may be used to meet this eligibility criterion with Medical Monitor approval.
- •Subjects with primary brain tumors may have received prior treatment with a TRK inhibitor but this is not required. Biopsies of brain tumors are not required for eligibility.
排除标准
- •Cytotoxic chemotherapy, biologic agent, investigational agent, or radiation therapy ≤ 3 weeks prior to the first dose of PBI-200 (6 weeks for nitrosoureas).
- •Subjects with either primary brain tumors or brain metastasis must have completed brain radiation therapy 12 weeks prior to the brain MRI obtained within 4 weeks of the first dose of PBI-
- •Small-molecule kinase inhibitors or hormonal agents ≤ 14 days and within 5 half-lives prior to the first dose of PBI-200.
研究组 & 干预措施
Phase 1 Dose Escalation
干预措施: PBI-200 (Drug)
Phase 2 Cohort Expansion
干预措施: PBI-200 (Drug)
结局指标
主要结局
Phase 1: Recommended Phase 2 Dose
时间窗: Approximately 12 months
Phase 2: Cohort B - ORR
时间窗: Through study completion, estimated as an average of 36 months
Assessed using Response Assessment in Neuro-Oncology (RANO) criteria
Phase 1: Number of patients with AEs
时间窗: Through study completion, estimated as an average of 36 months
Severity of AEs will be assessed according to the NCI CTCAE v5.0
Phase 2: Cohort A - Overall Response Rate (ORR)
时间窗: Through study completion, estimated as an average of 36 months
Assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
次要结局
- Phase 1: Area under the plasma drug concentration-time curve from 0 to 24 hours after one dose and after 28 doses(29 days)
- Duration of Response (DoR)(Through study completion, estimated as an average of 36 months)
- Phase 1: ORR(Through study completion, estimated as an average of 36 months)
- Progression-free Survival(Through study completion, estimated as an average of 36 months)