EUCTR2021-001029-32-IT进行中（未招募）1 期
A Phase 1/2 Study of PBI-200 in Subjects with NTRK-Fusion-Positive Advanced or Metastatic Solid Tumors
Pyramid Biosciences0 个研究点目标入组 74 人开始时间: 2021年8月24日最近更新:
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 74
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
入排标准
- 性别
- All
入选标准
- •1. 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
- •NTRK-gene amplified, locally advanced or metastatic solid tumor (Phase 1 only)
- •EWSR1-WT1-positive DSRCTs (Phase 1 only)
- •Note: Subjects with any grade of malignant glioma previously treated with systemic therapy are eligible. Subject’s prior treatment should include all approved regimens that have demonstrated a
- •survival advantage for the subject’s disease, stage, and line of therapy.
- •2. Phase 1
- •Subjects with NTRK-fusion-positive solid tumors other than primary brain tumors (non-brain primary 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
- •3. Phase 2
- •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 must have a documented on-target resistance mutation(s) (e.g., solvent
- •front, gatekeeper or xDFG mutation) as the mechanism of resistance to their prior
- •TRK-inhibitor treatment based on a tumor biopsy obtained following their most recent systemic therapy. 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. For these subjects who have previously been treated
- •with a TRK inhibitor, a tumor biopsy any time following TRK-inhibitor treatment is encouraged, and if analyzed for resistance mechanisms, must demonstrate an on-target
- •resistance mutation (e.g. solvent front, gatekeeper or xDFG mutation) as the mechanism of resistance to their prior TRK-inhibitor treatment. However, biopsies of brain tumors
- •are not required for eligibility.
- •Note: Subjects with NTRK-gene amplified tumors or EWSR1-WT1-positive DSRCTs are not eligible in Phase 2.
- •4. Subjects with brain tumors and brain metastasis must be neurologically stable. Subjects with ongoing neurologic signs, symptoms, or a history of seizures due to their intracranial tumor or
- •on antiseizure medication must be approved for enrollment by the Medical Monitor.
- •5. Age = 18 years at the time of signing the informed consent form (ICF)
- •6. Has provided written informed consent
- •7. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1. Subjects with PS = 2 may be approved by the Medical Monitor.
- •8. Acceptable liver, renal, hematologic, and coagulation function
- •Bilirubin = 1.5x ULN
- •AST, ALT = 3.0x ULN
- •Serum creatinine = 1.5x ULN and/or an estimated creatinine clearance of = 45 ml/min based on the Cockcroft-Gault formula
- •Absolute neutrophil count = 1000/mm3
排除标准
- •1. Cytotoxic chemotherapy, biologic agent, investigational agent, or radiation therapy = 3 weeks
- •prior to the first dose of PBI-200 (6 weeks for nitrosoureas). The interval may be reduced to
- •2 weeks for bone-only radiation therapy or investigational agents not expected to be
- •associated with AEs after 2 weeks of last administration, with Medical Monitor approval.
- •a. 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-200. The Medical Monitor may approve an interval of less than 12 weeks if
- •there is reasonable certainty of radiographic disease progression (e.g., new disease
- •outside the radiation therapy field following completion of the radiation therapy) or
- •histopathologic documentation of unequivocal disease progression
- •2. Small-molecule kinase inhibitors or hormonal agents = 14 days and within 5 half-lives prior
- •to the first dose of PBI-200
- •3. For subjects enrolled in Phase 2: Treatment with more than one prior TRK inhibitor.
- •Note: Subjects enrolled in the Phase 1 part of the study may have received more than one
- •TRK inhibitor.
- •4. Clinically significant AEs that have not returned to baseline or = Grade 1 based on NCI
- •CTCAE v5.0 unless approved by the Medical Monitor
- •5. Subjects with leptomeningeal disease (primary or metastatic) unless approved by the Medical
- •6. Major surgery = 6 weeks or minor surgery = 14 days prior to the first dose of PBI-200
- •7. Clinically significant intercurrent disease including but not limited to:
- •New York Heart Association Class III or IV heart failure
- •Myocardial infarction or stroke = 26 weeks prior to the first dose of PBI-200
- •Unstable angina within = 13 weeks prior to the first dose of PBI-200 unless the
- •underlying disease has been corrected by procedural intervention e.g., stent, bypass
- •Severe aortic stenosis
- •Uncontrolled arrhythmia. Medical Monitor approval of subjects with an arrhythmia is
- •Congenital long QT syndrome. Medical Monitor approval is required
- •QTc > 470 milliseconds by Fredericia criteria (QTcF) based on the average of 3 ECGs
- •taken approximately 1 minute apart and all within 10 minutes of each other. The subject
- •should be reclining for 5 minutes prior to ECGs. Local readings may be used for this
- •inclusion criterion.
- •Clinically significant active infection requiring systemic antibiotic, antiviral or antifungal
- •medication. Subjects must be medically stable, afebrile, and not taking antimicrobial
- •treatment for = 3 days prior to the first dose of PBI-200
- •8. Subjects taking sensitive substrates of CYP2B6, CYP2C8, CYP2C9 and CYP3A unless the
- •subject can safely discontinue these medications or change to comparable medications that
- •are not sensitive substrates of these CYPs
- •9. Subjects that are taking strong CYP3A inhibitors or inducers unless the subject can safely
- •discontinue these medications or change to comparable medications that are not strong
- •inhibitors or inducers of CYP3A at least 5 half-lives or 7 days prior to the first dose of
- •10. Human immunodeficiency virus (HIV) infection
- •11. Active hepatitis B or C infection
- •12. Has a history of another malignancy, unless the subject has been treated with curative intent
- •for this malignancy. Medical Monitor approval for enrollment is required for subjects with a
- •history of another malignancy. Study subjects with early-stage prostate cancer on active
- •surveillance may be enrolled
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