A Phase III Open-label, Multicenter Trial of Maintenance Therapy With Avelumab (MSB0010718C) Versus Continuation of First-line Chemotherapy in Subjects With Unresectable, Locally Advanced or Metastatic, Adenocarcinoma of the Stomach, or of the Gastro-esophageal Junction
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 499
- 试验地点
- 199
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
The purpose of this study was to demonstrate superiority of treatment with avelumab versus continuation of first-line chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Male or female participants greater than or equal to (>=) 18 years
- •Disease must be measurable by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
- •Participants with histologically confirmed unresectable locally advanced or metastatic adenocarcinoma of the stomach or gastro-esophageal junction (GEJ)
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at trial entry
- •Estimated life expectancy of more than 12 weeks
- •Adequate haematological, hepatic and renal functions defined by the protocol
- •Negative blood pregnancy test at Screening for women of childbearing potential
- •Highly effective contraception for both male and female participants if the risk of conception exists
- •Other protocol defined inclusion criteria could apply
排除标准
- •Prior therapy with any antibody or drug targeting T-cell coregulatory proteins
- •Concurrent anticancer treatment or immunosuppressive agents
- •Prior chemotherapy for unresectable locally advanced or metastatic adenocarcinoma of the stomach or gastro-esophageal junction (GEJ)
- •Tumor shown to be human epidermal growth factor 2 plus (HER2+)
- •Major surgery for any reason, except diagnostic biopsy, within 4 weeks of enrolment and/or if the participant has not fully recovered from the surgery within 4 weeks of enrolment
- •Participants receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the study treatment (with the exception of participants with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to <= 10 mg prednisone daily)
- •All participants with brain metastases, except those meeting the following criteria: a. Brain metastases have been treated locally, have not been progressing at least 2 months after completion of therapy, and no steroid maintenance therapy is required, and b. No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
- •Previous malignant disease (other than gastric cancer) within the last 5 years with the exception of basal or squamous cell carcinoma of the skin or carcinoma in situ (bladder, cervical, colorectal, breast)
- •Prior organ transplantation, including allogeneic stem-cell transplantation
- •Significant acute or chronic infections
- •Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
- •Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
- •Persisting toxicity related to prior therapy except alopecia
- •Neuropathy Grade > 3
- •Pregnancy or lactation
- •Known alcohol or drug abuse
- •History of uncontrolled intercurrent illness including hypertension, active infection, diabetes
- •Clinically significant (i.e., active) cardiovascular disease
- •All other significant diseases might impair the participant's tolerance of study treatment
- •Any psychiatric condition that would prohibit the understanding or rendering of informed consent and that would limit compliance with study requirements
- •Vaccination with live or live/attenuated viruses within 55 days of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
- •Legal incapacity or limited legal capacity
- •Participants will be excluded from the Induction Phase and the Maintenance Phase if administration of their chemotherapy would be inconsistent with the current local labelling (SmPC) (e.g., in regard to contraindications, warnings/precautions or special provisions) for that chemotherapy. Investigators should check updated labelling via relevant websites at the time of entry into the Induction Phase and the Maintenance Phase
- •Other protocol defined exclusion criteria could apply
研究组 & 干预措施
Chemotherapy + Best Supportive Care (BSC)
In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/LV or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion.
干预措施: Oxaliplatin (Drug)
Chemotherapy + Best Supportive Care (BSC)
In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/LV or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion.
干预措施: 5-Fluorouracil (Drug)
Chemotherapy + Best Supportive Care (BSC)
In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/LV or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion.
干预措施: Leucovorin (Drug)
Chemotherapy + Best Supportive Care (BSC)
In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/LV or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion.
干预措施: Capecitabine (Drug)
Chemotherapy + Best Supportive Care (BSC)
In Maintenance Phase, participants continued the same regimen of oxaliplatin-fluoropyrimidine doublet chemotherapy (oxaliplatin + 5FU/LV or oxaliplatin + capecitabine) as they received during the Induction Phase until disease progression, significant clinical deterioration, unacceptable toxicity, or discontinuation. Participants who were not deemed eligible to receive chemotherapy at the dose and schedule specified above received BSC alone once every 3 weeks. BSC was defined as treatment administered with the intent to maximize quality of life without a specific antineoplastic regimen and was based on Investigator's discretion.
干预措施: Best supportive care (Other)
Avelumab
In Maintenance phase, participants received avelumab as a 1-hour intravenous (IV) infusion at 10 milligrams per kilogram (mg/kg) once every 2-week treatment cycle until progressive disease or unacceptable toxicity or discontinuation.
干预措施: Avelumab (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: From randomization into maintenance phase up to 1276 days
Overall Survival was defined as the time from randomization to the date of death due to any cause. For participants who were still alive at the time of data analysis or who were lost to follow-up, OS time was censored at the date of last contact. OS was measured using Kaplan-Meier (KM) estimates.
次要结局
- Progression Free Survival (PFS) by Independent Review Committee (IRC)(From randomization into maintenance phase up to 1276 days)
- Best Overall Response (BOR) by Investigator Assessment(From randomization into maintenance phase up to 1276 days)
- Objective Response Rate (ORR) by Investigator Assessment(From randomization into maintenance phase up to 1276 days)
- Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Composite Index Score up to Safety Follow-up (Up to 152.3 Weeks)(Baseline, Week 3/4, Week 7, Week 13, Week 19, Week 25, Week 31, Week 37, Week 43, Week 49, Week 55, Week 61, Week 67, End of Treatment ( EOT up to 148 weeks) and Safety Follow-up (Up to 152.3 Weeks))
- Change From Baseline in European Quality of Life 5-dimensions Health Outcome Questionnaire Through Visual Analogue Scale up to Safety Follow-up (Up to 152.3 Weeks)(Baseline, Week 3/4, Week 7, Week 13, Week 19, Week 25, Week 31, Week 37, Week 43, Week 49, Week 55, Week 61, Week 67, End of Treatment ( EOT up to 148 weeks) and Safety Follow-up (Up to 152.3 Weeks))
- Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status Scale Score up to Safety Follow-up (Up to 152.3 Weeks)(Baseline, Week 3/4, Week 7, Week 13, Week 19, Week 25, Week 31, Week 37, Week 43, Week 49, Week 55, Week 61, Week 67, End of Treatment ( EOT up to 148 weeks) and Safety Follow-up (Up to 152.3 Weeks))
- Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22 ) Questionnaire Scores up to Safety Follow-up (Up to 152.3 Weeks)(Baseline, Week 3/4, Week 7, Week 13, Week 19, Week 25, Week 31, Week 37, Week 43, Week 49, Week 55, Week 61, Week 67, End of Treatment ( EOT up to 148 weeks) and Safety Follow-up (Up to 152.3 Weeks))
- Maintenance Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)(From randomization into maintenance phase up to 1276 days)
- Maintenance Phase: Number of Participants With Grade Change From Baseline to Worst On-Treatment Grade 4 Hematology Values(From baseline up to 1276 days)
- Maintenance Phase: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs(From randomization into maintenance phase up to 1276 days)
- Maintenance Phase: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities(From randomization into maintenance phase up to 1276 days)
- Maintenance Phase: Number of Participants With Shift in Eastern Cooperative Oncology Group (ECOG) Performance Status Score to 1 or Higher Than 1(From randomization into maintenance phase up to 1276 days)