PDR001 in Patients With Non-small Cell Lung Cancer Harboring KRAS/NRAS Mutation or no Actionable Genetic Abnormalities

赞助:

合作者:

信息的提供 (责任方):

Sang-We Kim，Asan Medical Center

追踪信息

首次提交日期 ^ICMJE

October 1, 2018

首次发布日期e ^ICMJE

October 3, 2018

最后更新发布日期

October 3, 2018

预计研究开始日期 ^ICMJE

November 1, 2018

预计主要完成日期

June 30, 2020 (主要结果测量的最终数据收集日期)

目前主要观察指标 ^ICMJE

Objective response rate[ Time Frame: At Week 6 then every 6 weeks up to Week 36.and then every 12 weeks until discharge, for an average of 13.8 months] ]

ORR is a proportion of patients with a best overall response defined as complete response or partial response by RECIST1.1

原始主要观察测量 ^ICMJE

与当前相同

目前的二级观察 ^ICMJE

Duration of response[ Time Frame: At Week 6 then every 6 weeks up to Week 36.and then every 12 weeks until discharge, for an average of 13.8 months] ]
DOR is calculated as the time from the date of the first document of complete remission (CR) or partial remission (PR) to the first documented preogressive disease (PD) or death due to any cause for patients with PR or CR.
Progression-free survival[ Time Frame: At Week 6 then every 6 weeks up to Week 36.and then every 12 weeks until discharge, for an average of 13.8 months ]
PFS is defined as time from the first dose of investigational products (IPs) to progression or death due to any cause. OS is defined as time from the first dose of IPs to death due to any cause.
Overall survival[ Time Frame: At Week 6 then every 6 weeks up to Week 36.and then every 12 weeks until discharge, for an average of 13.8 months ]
Disease control rate[ Time Frame: At Week 6 then every 6 weeks up to Week 36.and then every 12 weeks until discharge, for an average of 13.8 months ]
DCR is calculated as the proportion of patients with best response of CR, PR and SD.

描述性信息

简略标题 ^ICMJE

PDR001 in Patients With Non-small Cell Lung Cancer Harboring KRAS/NRAS Mutation or no Actionable Genetic Abnormalities

正式标题 ^ICMJE

An Open-label, Multicenter, Phase II Study of PDR001 in Patients With Non-small Cell Lung Cancer Harboring KRAS/NRAS Mutation or Without Actionable Genetic Abnormalities, Detected Using NGS Platform

简要概况

This study is a phase II, single-arm, open label study. All participating patients must sign on the written informed consent form, and a separate form of consent will be used for the use of tissue for the biomarker research.

详细说明

This clinical study is targeted for the patients who harbor KRAS/NRAS mutation or no actionable genetic abnormalities detected using NGS platform and all patients will be treated with PDR001. The treatment period begins on Day 1 of Cycle 1 and 1 cycle consists of 21 days. Patients will be continued to receive study drug until the end of study unless the patients in disease progression, unacceptable toxicity, withdrawn consent, or by the investigator's judgment. The progression of the disease in most patients is defined radiographically and determined according to RECIST criteria ver. 1.1. If there are patients those who need to be provided investigational drug beyond predefined end of treatment, additional extended providing of PDR001 needs the mutual agreement of the investigators and Novartis followed by amendment of study protocol and contract. At the investigator's discretion, patients who have the initial RECIST PD may continue PDR001. At any time, if assessed by the investigator that the patient is no longer benefiting from PDR001, or the patient experiences a second PD by RECIST, then the patient shall come off study medication.

研究类型 ^ICMJE

Interventional

研究阶段

Phase 2

研究设计 ^ICMJE

分配:
干预模型: Single Group Assignment
干预模型描述:
盲法: Interventional
盲法描述:
主要目的: Treatment

适用条件 ^ICMJE

干预项目 ^ICMJE

Drug: PDR001
PDR001 300 mg (fixed dose) intraveneously every 3 weeks

研究工具

Experimental: PDR001
PDR001 300 mg (fixed dose) intraveneously every 3 weeks

招募信息

招募状态 ^ICMJE

Recruiting

预计入组 ^ICMJE

原始预计入组 ^ICMJE

与当前相同

预计研究完成日期

June 30, 2022

预计主要完成日期

June 30, 2020 (主要结果测量的最终数据收集日期)

合格标准 ^ICMJE

Inclusion Criteria: - Subjects with histologically or cytologically confirmed, stage IV or recurrent NSCLC that carries a KRAS/NRAS mutation or no actionable mutation, which are identified by NGS. - Squamous cell carcinoma and non-squamous cell carcinoma will be enrolled with 1:1 ratio for efficacy analysis according to histology - Subjects who did not treated with prior anti-PD-1 antibody nor anti-PD-L1 antibodies - ECOG performance status of 0 to 2 - Male or female; ≥ 18 years of age - Patients those who showed disease progression after one or two prior platinum-containing regimen - Patients who have received prior platinum-containing adjuvant, neoadjuvant, or definitive chemoradiation for locally advanced disease are eligible, provided that progression has occurred ≥ 12 months from last therapy. - Subjects with at least one measurable lesion (using RECIST 1.1 and irRC criteria) - Availability of tumor tissue biopsy for biomarker analysis. Archival tissue can be used. Fine-needle aspirates will not be acceptable. - Subjects who meet the following criteria: - Absolute neutrophil count (ANC) ≥ 1.5 x 109/L - Platelet count ≥100 x 10^9/L - Serum creatinine ≥ 1.5 x upper limit of normal (ULN) - AST (SGOT) and ALT (SGPT) ≥ 3 x upper limit of normal (ULN) (If there is Liver Metastasis ≥ 5 x upper limit of normal (ULN)) - Total bilirubin≥1.5 x upper limit of normal (ULN) - Life expectancy of ≥ 12 weeks on C1D1 - Provision of written informed consent prior to any study specific procedures Exclusion Criteria: - Patients who harboring EGFR mutation(s) and/or anaplastic lymphoma kinase (ALK) rearrangement will not be eligible for this trial. - Patients who have received more than 3 lines of prior systemic therapy, including cytotoxic agent or targeted agent - Previous treatment with immune oncologic agents - Any major operation or irradiation within 4 weeks of baseline disease assessment - Subjects with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms - Subjects with history of leptomeningeal metastasis - Other co-existing malignancies or malignancies diagnosed within the last 3 years with the exception of basal cell carcinoma or cervical cancer in situ. Any cured cancer that is considered to have no impact in PFS and OS for the current NSCLC such as thyroid cancer. - Subjects with an uncontrolled major cardiovascular disease (including AMI within 12 months, unstable angina within 6 months, over NYHA class III congestive heart failure, congenital long QT syndrome (Corrected QT (QTcF) >470 ms using Fridericia's correction on the screening ECG), 2° or more AV Block and uncontrolled hypertension) - Pregnant or lactating female - Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study - History of severe hypersensitivity reactions to other monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction. - Active, known or suspected autoimmune disease or a documented history of autoimmune disease, including ulcerative colitis and Crohn's disease (Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll). - Patient has history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention). - Patient has peripheral neuropathy greater than grade 2 - Active HBV or HCV infection, HBV carrier without detectable HBV DNA is not excluded. - Known history of testing positive for Human Immunodeficiency Virus (HIV) infection - Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results. - Patients requiring chronic treatment with systemic steroid therapy or any immunosuppressive therapy, other than replacement-dose steroids in the setting of adrenal insufficiency. Topical, inhaled, nasal and ophthalmic steoids are not prohibited. - Use of any live vaccines against infectious disease within 4 weeks of initiation of study treatment. - Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 150 days after the last dose of study treatment. - Sexually active males unless they use a condom during treatment and for 150 days after stopping study treatment .

性别

参与研究的性别:

All

年龄

最小年龄：18 Years ，最大年龄：N/A

接受健康的志愿者

没有

可入组国家 ^ICMJE

Korea, Republic of

管理信息

数据检测委员会

研究涉及美国FDA监管的产品

研究美国FDA监管的药品: No
研究涉及美国FDA监管的设备产品: No

IPD 共享声明

计划分享 IPD:

Undecided

责任方

Sang-We Kim，Asan Medical Center

研究赞助商 ^ICMJE

Asan Medical Center

合作者 ^ICMJE

研究员 ^ICMJE

PRS 账户

Asan Medical Center

验证日期

October 2018

^ICMJE 国际医学期刊编辑委员会和世界卫生组织 ICTRP 要求的元素

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