NCT04154956终止3 期
Randomized, Open-label, Phase 3 Study of SAR408701 Versus Docetaxel in Previously Treated, Metastatic Nonsquamous, Non-small-cell Lung Cancer Patients With CEACAM5-positive Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Sanofi
- 入组人数
- 389
- 试验地点
- 338
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
Primary Objectives:
- Study was designed with multiple primary endpoints analyzed on randomized participants at the time of the cut-off date for each given analysis (progression free survival [PFS] and overall survival [OS])
- Study success was defined either on PFS or OS
- The primary objective was to determine whether tusamitamab ravtansine improves the progression free survival (PFS) when compared to docetaxel in participants with metastatic non-squamous non-small-cell lung cancer (NSCLC) expressing CEACAM5 greater than or equal to 2+ in intensity in at least 50% of the tumor cell population and previously treated with standard-of-care platinum-based chemotherapy and an immune checkpoint inhibitor (ICI)
- The primary objective was to determine whether tusamitamab ravtansine improves the overall survival (OS) when compared with docetaxel in participants with metastatic non-squamous NSCLC expressing CEACAM5 greater than or equal to 2+ in intensity in at least 50% of the tumor cell population and previously treated with standard-of-care platinum-based chemotherapy and an immune checkpoint inhibitor.
Secondary Objectives:
- Compared the objective response rate (ORR) of tusamitamab ravtansine with docetaxel
- Compared the health-related quality of life (HRQOL) of tusamitamab ravtansine with docetaxel
- Evaluated the safety of tusamitamab ravtansine compared to docetaxel
- Assessed the duration of response (DOR) of tusamitamab ravtansine as compared with docetaxel
详细描述
The median expected duration of study per participant was estimated as median 9 months in docetaxel arm (1 month for screening, 4 months for treatment, and 4 months for the EOT and follow-up visits) and 12.5 months in SAR408701 arm (1 month for screening, 6.5 months for treatment, and 5 months for end of treatment follow-up).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •At least 18 years of age or above (or country's legal age of maturity if above 18 years) and signed the informed consent.
- •Histologically or cytologically proven diagnosis of non-squamous NSCLC with metastatic disease at study entry; progression after platinum-based chemotherapy and immune checkpoint inhibitor.
- •Participants with carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 5 expression of greater than or equal to 2+ in archival tumor sample (or if not available, fresh biopsy sample) involving at least 50% of the tumor cell population as demonstrated prospectively by central laboratory via immune histochemistry (IHC).
- •At least one measurable lesion by RECIST v1.1 as determined by local site investigator /radiologist assessment.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •A female participant who agreed to use highly effective contraceptive methods during and for at least 7 months after the last dose of study intervention.
- •A male participant who agreed to use highly effective contraception methods during and for at least 6 months after the last dose of study intervention.
排除标准
- •Participants with untreated brain metastases and history of leptomeningeal disease. if previously treated brain metastases no documentation of non-progressive disease in brain by imaging performed at least 4 weeks after CNS directed treatment and at least 2 weeks prior to the first dose of study intervention.
- •Significant concomitant illnesses, including all severe medical conditions that would impair the participation in the study or interpretation of the results.
- •History within the last 3 years of an invasive malignancy other than the one treated in this study, with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment.
- •Non-resolution of any prior treatment related toxicity to less than grade 2 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (V) 5.0, except for alopecia, vitiligo and active thyroiditis controlled with hormonal replacement therapy
- •History of known acquired immunodeficiency syndrome (AIDS) related illnesses or known HIV disease requiring antiretroviral treatment, or unresolved viral hepatitis
- •Previous history of and/or unresolved corneal disorders. The use of contact lenses was not permitted.
- •Concurrent treatment with any other anticancer therapy.
- •Prior treatment with docetaxel or maytansinoid derivatives (DM1 or DM4 antibody drug conjugate) or any drug targeting CEACAM
- •Contraindicated the use of corticosteroid premedication.
- •Previous enrollment in this study and current participation in any other clinical study involving an investigational study treatment or any other type of medical research.
- •Poor bone marrow, liver or kidney functions
- •Hypersensitivity to any of the study interventions, or components thereof (EDTA), or drug (paclitaxel, polysorbate 80) or other allergy that, in the opinion of the Investigator, contraindicated participation in the study.
- •The above information was not intended to contain all considerations relevant to a potential participation in a clinical trial.
研究组 & 干预措施
Docetaxel
Active Comparator
Participants received docetaxel 75 mg/m^2 by IV infusion, once every 3 weeks (Q3W) until objective PD, unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 115 weeks).
干预措施: Docetaxel (Drug)
SAR408701 (tusamitamab ravtansine)
Experimental
Participants received tusamitamab ravtansine 100 milligrams per square meter (mg/m^2) by intravenous (IV) infusion, once every 2 weeks (Q2W) until objective progressive disease (PD), unacceptable adverse event/toxicity, upon participant's request to stop treatment, or Investigator decision, whichever occurred first (maximum exposure: 147 weeks).
干预措施: SAR408701 (Drug)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: Tumor assessments performed at screening, and every 8 weeks +/-5 days thereafter, up to 189 weeks
PFS was defined as the time from the date of randomization to the date of the first documentation of objective PD as assessed by radiological review committee (IRC) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) definitions or death due to any cause before the study cut-off date, whichever occurred first. PD was defined as unequivocal progression of existing non-target lesions; appearance of 1 or more new lesions; at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm).
Overall Survival (OS)
时间窗: From date of first study treatment administration (Day 1) until the date of death due to any cause, up to 189 weeks
Overall survival was defined as the time from date of randomization to date of death due to any cause.
次要结局
- Objective Response Rate (ORR)(Tumor assessments performed at screening, and every 8 weeks +/-5 days thereafter, up to 189 weeks)
- Time to Deterioration (TTD) in Disease-related Symptoms as Determined by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire and Lung Cancer-specific Module With 13 Items (EORTC QLQ LC-13)(Predose on Day 1 of Cycle 1, then on Day 1 of every 2 docetaxel Cycles, or every 3 tusamitamab ravtansine Cycles (i.e., every 6 weeks) up to 30 days after the last dose of study drug administration, up to 151 weeks)
- TTD in Physical Function as Determined by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Cancer-specific Module With 30 Items (EORTC QLQ C30)(Predose on Day 1 of Cycle 1, then on Day 1 of every 2 docetaxel Cycles, or every 3 tusamitamab ravtansine Cycles (i.e., every 6 weeks) up to 30 days after the last dose of study drug administration, up to 151 weeks)
- TTD in Role Function Measured by EORTC QLQ C30(Predose on Day 1 of Cycle 1, then on Day 1 of every 2 docetaxel Cycles, or every 3 tusamitamab ravtansine Cycles (i.e., every 6 weeks) up to 30 days after the last dose of study drug administration, up to 151 weeks)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)(From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment administration, up to 151 weeks)
- Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology Parameters(From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment administration, up to 151 weeks)
- Number of Participants With PCSA in Clinical Chemistry(From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment administration, up to 151 weeks)
- Duration of Response (DOR)(Tumor assessments performed at screening, and every 8 weeks +/-5 days thereafter, up to 189 weeks)
研究者
研究点 (338)
Loading locations...
相似试验
招募中
3 期
Investigate the Efficacy of Chemotherapy in Patients With Positive ctDNA After Surgery and Adjuvant Chemotherapy for a Stage III Colorectal CancerColon or Upper Rectum AdenocarcinomaNCT06197425Centre Hospitalier Universitaire Dijon1,660
已完成
3 期
Study Comparing Rovalpituzumab Tesirine Versus Topotecan in Subjects With Advanced or Metastatic Small Cell Lung Cancer With High Levels of Delta-like Protein 3 (DLL3) and Who Have First Disease Progression During or Following Front-line Platinum-based Chemotherapy (TAHOE)Small Cell Lung CancerNCT03061812AbbVie444
已完成
3 期
A Study of Atezolizumab Compared With Docetaxel in Non-Small Cell Lung Cancer (NSCLC) After Failure With Platinum-Containing ChemotherapyCarcinoma, Non-Small-Cell LungNCT02813785Hoffmann-La Roche565
已完成
3 期
Comparison of Sofosbuvir/Velpatasvir Fixed Dose Combination for 12 Weeks With Sofosbuvir and Ribavirin for 12 Weeks in Adults With Chronic Genotype 2 HCV InfectionHepatitis C Virus InfectionNCT02220998Gilead Sciences269
已完成
3 期
Efficacy and Safety of Trastuzumab Emtansine in Chinese Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Locally Advanced or Metastatic Breast CancerBreast CancerNCT03084939Hoffmann-La Roche351