A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 160 in Subjects With Non-Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Amgen
- 入组人数
- 3
- 试验地点
- 4
- 主要终点
- Number of Participants Who Experience One or More Dose-limiting Toxicities (DLT)
研究概览
简要总结
This study aims to evaluate the safety and tolerability of AMG 160 and to evaluate the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D).
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
- •Participant has provided informed consent prior to initiation of any study specific activities/procedures.
- •Histologically or cytologically confirmed stage 4 or recurrent non-squamous NSCLC (Part 1); histologically or cytologically. confirmed stage 4 or recurrent NSCLC (Part 2 only, squamous cell histology/cytology allowed in Part 2).
- •Without a driver mutation: disease progression following at least one line of prior chemotherapy and at least 1 prior anti-programmed cell death protein 1 (PD1)/programmed death-ligand 1 (PDL1) therapy.
- •With a driver mutation must experience disease progression on at least 1 targeted therapeutic agent to be eligible.
- •Detectable prostate-specific membrane antigen (PSMA) expression by PSMA positron emission tomography (PET)/computed tomography (CT) imaging.
- •Measurable disease by modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0- 2.
排除标准
- •Radiographic evidence of intratumor cavitation, major blood vessel invasion or encasement by cancer.
- •Untreated or symptomatic brain metastases and leptomeningeal disease.
- •History of hemoptysis within 3 months prior to first dose.
- •History or evidence of gastrointestinal inflammatory bowel disease (ulcerative colitis or Crohn disease).
- •Myocardial infarction, unstable angina, cardiac arrhythmias requiring medication, and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months prior to start of dosing.
- •Vasculitis or grade 3/4 gastrointestinal bleeding within 3 months prior to first dose; vascular disease (eg, aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months of first dose.
- •Gastrointestinal (GI) perforation and/or fistulae within 6 months prior to start of dosing.
- •Interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with treatment.
- •Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation).
- •Chronic systemic corticosteroid therapy or any other immunosuppressive therapies unless stopped 7 days prior to first dose.
- •Any biological therapy or immunotherapy within 3 weeks of start of first dose.
- •Major surgery within 4 weeks of first dose.
- •Infection requiring IV antimicrobials for management within 7 days of dosing.
- •Known human immunodeficiency virus (HIV) infection, hepatitis C infection.
- •Active autoimmune disease
研究组 & 干预措施
Part 1: Dose Exploration
The dose exploration part of the study will estimate the MTD and/or the RP2D.
干预措施: AMG 160 (Drug)
Part 2: Dose Expansion - Cohort 1 Non-squamous NSCLC
Participants with non-squamous non-small cell lung cancer (NSCLC) will be administered the RP2D identified from the dose exploration part of the study.
干预措施: AMG 160 (Drug)
Part 2: Dose Expansion - Cohort 2 Squamous NSCLC
Participants with squamous NSCLC will be administered the RP2D identified from the dose exploration part of the study.
干预措施: AMG 160 (Drug)
结局指标
主要结局
Number of Participants Who Experience One or More Dose-limiting Toxicities (DLT)
时间窗: Day 1 to Day 28
DLT were defined as any adverse event (AE) with an onset within first 28 days following first dose of AMG 160 meeting pre-specified criteria unless clearly attributable to causes other than AMG 160 treatment.
Number of Participants Who Experience One or More Treatment-emergent AE (TEAE)
时间窗: Median (min, max) time from first dose to 30 days after the last dose, end of study or start of new anti-cancer therapy; whichever is earlier, was 66 (52, 100) days
An AE is any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. A TEAE is any AE that occurred on or after first dose of study treatment up to 30 days after the last dose or End of Study date or start of new anti-cancer therapy, whichever is earlier. A treatment-related TEAE is any TEAE that, per investigator review, has a reasonable possibility of being caused by the study treatment. Any abnormal vital signs measurement or clinical laboratory test result, including those that worsened from Baseline, that were considered clinically significant in the medical and scientific judgement of the investigator were reported as an AE.
次要结局
- Time to Response Per Modified RECIST v1.1(Median (min, max) time from first dose to end of study was 100 (94, 122) days)
- Time to Clinical Progression(Median (min, max) time from first dose to end of study was 100 (94, 122) days)
- Duration of Response (DOR) Per Modified RECIST v1.1(Median (min, max) time from first dose to end of study was 100 (94, 122) days)
- Time to Subsequent Therapy(Median (min, max) time from first dose to end of study was 100 (94, 122) days)
- Radiographic Progression Free Survival (PFS) Per Modified RECIST v1.1(Median (min, max) time from first dose to end of study was 100 (94, 122) days)
- Clinical PFS Per Modified RECIST v1.1(Median (min, max) time from first dose to end of study was 100 (94, 122) days)
- Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1(Median (min, max) time from first dose to end of study was 100 (94, 122) days)
- Time to Progression Per Modified RECIST v1.1(Median (min, max) time from first dose to end of study was 100 (94, 122) days)
- Overall Survival (OS)(Median (min, max) time from first dose to end of study was 100 (94, 122) days)