PRIMAL STUDY: A Phase 1b, Open-label, Multicenter, Multinational Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) Combined With Docetaxel (PDoc) in Subjects With Recurrent Previously Treated Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 16
- 试验地点
- 7
- 主要终点
- Number of Participants With the Indicated Type of Adverse Events for PEGPH20 and Docetaxel
研究概览
简要总结
A Phase 1b study for participants with Stage IIIB/IV Non-Small Cell Lung Cancer (NSCLC) to participate in 1 of 2 portions of this study. The first portion is Dose Escalation in which participants are tested with PEGPH20 at various doses (1.6, 3.0, 2.2 and 2.8 micrograms/kilogram (ug/kg)) in addition to dosing with the standard dose of docetaxel (PDoc) of 75 milligrams/meter squared (mg/m^2) once every 21-day cycle. Based on observations on the safety and tolerability of study treatment from dose escalation cohorts dosed to date (1.6 and 3.0 ug/kg of PEGPH20), two additional dose levels will be tested, 2.2 and 2.8 ug/kg. Up to 30 additional participants may be enrolled to test these dose levels. The second portion of Phase 1b is Cohort Expansion in which the recommended Phase 2 dose (RP2D) of PDoc identified in dose escalation is administered every 21 days to approximately 50 participants with high hyaluronan (HA-high) prospectively measured in their tumor tissue.
研究设计
- 研究类型
- Interventional
- 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
- •Signed, approved Informed Consent.
- •Histologically confirmed and documented previously treated Stage IIIB/IV Non-Small Cell Lung Cancer (NSCLC), having failed 1 previous platinum chemo regimen for locally advanced or metastatic disease.
- •Cohort Expansion: Available archival tumor tissue block or 5-10 unstained, consecutive core biopsy slides from one archival tumor block that meet specific tissue requirements.
- •Cohort Expansion: Participants must be determined to be hyaluronidase (HA)-high based on tumor biopsy that meets the requirements noted in the previous inclusion criterion.
- •Cohort Expansion: One or more tumors measurable on computed tomography/magnetic resonance imaging (CT/MRI) scan per Response Evaluation Criteria on Solid Tumors (RECIST) v 1.1 (Eisenhauer 2009; Appendix C).
- •Participants may have failed a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) therapy for advanced disease.
- •Participants that are known to be epidermal growth factor (EGFR)-activating mutation positive must have received an EGFR inhibitor.
- •Participants known to be anaplastic lymphoma kinase (ALK)-fusion/rearrangement mutation positive must have received an ALK inhibitor.
- •Most prior therapies and prior targeted therapy are allowed and these specific therapies are detailed in the protocol.
- •Life expectancy - =/> 3 months, Eastern Cooperative Oncology Group status = 0 or
- •Negative urine or serum pregnancy test within 7 days before Day 1 (first dose of study medication) if female participants is of childbearing potential (WOCBP).
- •Men and women agreement to use effective contraceptive method. For WOCBP and for men, agreement to use an effective contraceptive method from the time of screening throughout the study until 1 month for WOCBP or 6 months for men after administration of the last dose of any study medication.
- •Specific ranges/levels of Screening labs that are acceptable per protocol.
- •Age >/= 18 years.
排除标准
- •Previous treatment with docetaxel.
- •Failed more than 3 treatment regimens for locally advanced or metastatic NSCLC.
- •New York Heart Assoc Class III or IV cardiac disease, myocardial infarction within the past 12 months before screening, or pre-existing atrial fibrillation.
- •History of cerebrovascular accident or transient ischemic attack.
- •Pre-existing carotid artery disease.
- •Previous history of pulmonary embolism or pulmonary embolism found on screening exam.
- •No ongoing requirement for corticosteroids
- •Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy at time of screening.
- •Known infection with HIV and active infection with hepatitis B or C.
- •Known allergy to hyaluronidase or any constituents of docetaxel formulation.
- •Current use (within 10 days of day 1) of megestrol acetate.
- •Chronic concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole).
- •Women currently pregnant or breast feeding.
- •Intolerance to dexamethasone, as determined by Investigator.
- •History of another primary cancer within the last 3 years that required treatment, with the exception of non-melanoma skin cancer, early stage prostate cancer, or curatively treated cervical carcinoma in situ.
- •Any other disease, metabolic dysfunction, physical exam finding, or clinical lab finding that leads to reasonable suspicion of disease that contraindicates the use of an investigational drug that might affect interpretation of results or render subject at high risk for treatment complications.
- •In opinion of Investigator, make subject unsuitable for study.
- •Hypersensitivity to the active substance or ingredients of PEGPH20 and docetaxel.
- •Subject's inability to comply with study and follow-up procedures, as judged by the Investigator.
研究组 & 干预措施
PEGPH20 + Docetaxel
PEGylated recombinant human hyaluronidase PH20 (PEGPH20) (1.6, 3.0, or 2.2 micrograms per kilogram (ug/kg)) was administered on Day 1 of each 21-day cycle (every 3 weeks) as an intravenous (IV)-infusion over 10 minutes, approximately 1 milliliter/minute (mL/min) (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 milligrams/meter squared (mg/m^2)) was administered on Day 2 of each 21-day cycle.
干预措施: PEGylated recombinant human hyaluronidase PH20 (Drug)
PEGPH20 + Docetaxel
PEGylated recombinant human hyaluronidase PH20 (PEGPH20) (1.6, 3.0, or 2.2 micrograms per kilogram (ug/kg)) was administered on Day 1 of each 21-day cycle (every 3 weeks) as an intravenous (IV)-infusion over 10 minutes, approximately 1 milliliter/minute (mL/min) (a window of +2 minutes allowed, i.e., infusion could be 10 to 12 minutes). Docetaxel (75 milligrams/meter squared (mg/m^2)) was administered on Day 2 of each 21-day cycle.
干预措施: Docetaxel (Drug)
结局指标
主要结局
Number of Participants With the Indicated Type of Adverse Events for PEGPH20 and Docetaxel
时间窗: From date of first dose until 30 days after the last dose of study treatment, up to approximately 1 year 10 months
Throughout the Treatment Period, the assessment of safety was based on AEs, including deaths, non-serious AEs, and serious adverse events, AEs leading to discontinuation of study treatment, and results of vital sign measurements and clinical laboratory assessments (including hematology, clinical chemistry, coagulation parameters, and urinalysis). Additionally, thromboembolic (TE) events were deemed by the Sponsor as AEs of special interest. AEs and laboratory values were graded for severity using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
Number of Dose Limiting Toxicities (DLTs)
时间窗: Cycle 1 (Day 1 through Day 21) (1 Cycle = 21 days)
DLTs were defined as adverse events (AEs) that occurred during Cycle 1 in the Dose Escalation portion of the study, and deemed by the Investigator as related to study treatment.
Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of PEGPH20
时间窗: Cycle 1 of Dose Escalation portion (Cycle 1 = 21 days)
次要结局
- Phase 1b: Time to Maximum Plasma Concentration (Tmax) of PEGPH20 and Docetaxel(PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2)
- Phase 1b: Volume of Distribution (Vd) of PEGPH20 and Docetaxel(PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2)
- Phase 1b: Maximum Plasma Concentration (Cmax) of PEGPH20 and Docetaxel(PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2)
- Phase 1b: Minimum Plasma Concentration (Cmin) of PEGPH20 and Docetaxel(PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2)
- Phase 1b: Area Under the Plasma Concentration-Time Curve for PEGPH20 and Docetaxel(PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2)
- Phase 1b: Terminal Half-life (t1/2) of PEGPH20 and Docetaxel(PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2)
- Disease Control Rate (DCR)(From date of treatment start until disease progression or up to data cutoff date (30 Nov 2016), for up to approximately 1 year 9 months)
- Phase 1b: Clearance (CL) of PEGPH20 and Docetaxel(PEGPH20: multiple time points C1D1 and all subsequent Cycles; Docetaxel: multiple time points C1D2, C2D2 and C3D2)
- Objective Response Rate (ORR)(From date of treatment start until disease progression or up to data cutoff date (30 Nov 2016), for up to approximately 1 year 9 months)
- Duration of Response (DoR)(From date of first CR or PR until the date of first documentation of disease progression or date of death, assessed up to data cutoff date (30 Nov 2016))
- Progression-free Survival (PFS)(From date of treatment start until date of first documentation of progressive disease or death from any cause, assessed up to 1 year 9 months)