Open-label Study of Tusamitamab Ravtansine (SAR408701) in Combination With Ramucirumab in Participants Previously Treated for Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma With CEACAM5-positive Tumors
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Sanofi
- 入组人数
- 35
- 试验地点
- 21
- 主要终点
- Part 1: Number of Participants With Study-Drug Related Dose Limiting Toxicities (DLTs)
研究概览
简要总结
Primary Objectives:
Part 1: to confirm the recommended tusamitamab ravtansine loading dose Q2W in combination with ramucirumab in advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma population
Part 2: to assess the antitumor activity of tusamitamab ravtansine loading dose Q2W in combination with ramucirumab in advanced gastric or GEJ adenocarcinoma
Secondary Objectives:
- To assess safety and tolerability
- To assess durability of response (DOR)
- To assess progression-free survival (PFS)
- To assess the disease control rate (DCR)
- To assess the pharmacokinetics (PK)
- To assess the immunogenicity
详细描述
34 weeks (up to 4 weeks for screening, a median of 18 weeks for treatment, and a median of 12 weeks for end-of-treatment assessments and the safety follow-up visit).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Histologically or cytologically confirmed diagnosis of gastric or GEJ adenocarcinoma
- •Metastatic disease or locally advanced, unresectable disease
- •Participants who have measurable target lesion
- •Participants with high carcinoembryonic antigen-related cell adhesion molecule (CEACAM5) expression as per central assessment on tumor biospsy
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Female participant who agrees to use effective contraceptive methods during and for at least 7 months after the last dose of treatment administration
- •Male participant who agrees to use effective contraception methods during and for at least 4 months after the last dose of treatment administration
- •Signed informed consent
排除标准
- •Untreated brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression
- •Significant concomitant illness
- •History within the last 3 years of an invasive malignancy other than that treated in this study
- •Known uncontrolled infection
- •Nonresolution of any prior treatment-related toxicity
- •Unresolved corneal disorder or any previous corneal disorder considered by an ophthalmologist to predict higher risk of drug-induced keratopathy
- •Use of contact lenses
- •Radiographic evidence of major airway or blood vessel invasion or intratumor cavitation
- •History of uncontrolled hereditary or acquired thrombotic disorder or history of aneurism
- •Major surgery within 28 days prior to Day 1/first IMP infusion; subcutaneous venous access device placement within 7 days prior to Day 1; or postoperative bleeding complications or wound complications from a surgical procedure performed in the last 2 months
- •History of gross hemoptysis (defined as bright red blood or ≥1/2 teaspoon) within 2 months before the first treatment administration
- •Any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months before the first administration of treatment administration
- •Uncontrolled arterial hypertension (systolic ≥150 mmHg or diastolic ≥90 mmHg) despite standard medical management.
- •Serious or nonhealing wound, skin ulcer, or bone fracture within 28 days before the first administration of treatment administration
- •Gastrointestinal (GI) perforation and/or fistulae within 6 months prior to first administration of treatment administration
- •Significant bleeding disorders, vasculitis, or Grade 3-4 gastrointestinal (GI) bleeding within 3 months before the first administration of study intervention.
- •Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection Crohn's disease, ulcerative colitis, or chronic diarrhea
- •Medical condition requiring concomitant administration of a medication with a narrow therapeutic window and metabolized by CYP450 or a strong CYP3A inhibitor
- •Concurrent treatment with any other anticancer therapy
- •Prior treatment targeting CEACAM5 or containing maytansinoid DM1 or DM4 or ramucirumab or taxane or targeting VEGF/VEGFR Poor organ function
- •The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
研究组 & 干预措施
Tusamitamab ravtansine+Ramucirumab
Participants received ramucirumab 8 milligram/kilogram (mg/kg) via intravenous (IV) infusion followed by tusamitamab ravtansine loading dose at 170 mg/meter square (m^2) via IV infusion on Cycle 1 Day 1 (each cycle was 2 weeks); and then ramucirumab 8 mg/kg via IV infusion followed by tusamitamab ravtansine 100 mg/m^2 via IV infusion at Cycle 2 and every 2 weeks (Q2W) in all subsequent cycles until disease progression, unacceptable adverse event (AE), death, initiation of a new anticancer therapy, or the participant's or investigator's decision to stop the treatment.
干预措施: Ramucirumab (CYRAMZA®) (Drug)
Tusamitamab ravtansine+Ramucirumab
Participants received ramucirumab 8 milligram/kilogram (mg/kg) via intravenous (IV) infusion followed by tusamitamab ravtansine loading dose at 170 mg/meter square (m^2) via IV infusion on Cycle 1 Day 1 (each cycle was 2 weeks); and then ramucirumab 8 mg/kg via IV infusion followed by tusamitamab ravtansine 100 mg/m^2 via IV infusion at Cycle 2 and every 2 weeks (Q2W) in all subsequent cycles until disease progression, unacceptable adverse event (AE), death, initiation of a new anticancer therapy, or the participant's or investigator's decision to stop the treatment.
干预措施: Tusamitamab ravtansine (SAR408701) (Drug)
结局指标
主要结局
Part 1: Number of Participants With Study-Drug Related Dose Limiting Toxicities (DLTs)
时间窗: From Cycle 1 Day 1 to Cycle 2 Day 14; approximately 28 days
The following AEs occurred during the first 2 cycles of treatment, unless due to disease progression or to a cause obviously unrelated to study drug, were considered DLTs: * Grade 4 neutropenia for 7 or more consecutive days. * Grade 3 to 4 neutropenia complicated by fever (temperature \>=38.5 degree Celsius on more than 1 occasion) or microbiologically or radiographically documented infection. * Grade \>=3 thrombocytopenia associated with clinically significant bleeding requiring clinical intervention. * Grade 4 non-hematologic AE. * Grade \>=3 keratopathy. In addition, any other AE that the Investigators and sponsor deemed to be dose limiting, regardless of its grade, was also considered as DLT.
Objective Response Rate (ORR)
时间窗: Tumor assessments performed at Baseline (Day 1), then every 6 weeks (±7 days) thereafter, approximately 88.1 weeks
The ORR was defined as percentage of participants with confirmed complete response (CR) or partial response (PR) as best overall response (BOR) determined per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
次要结局
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)(From the first study drug administration (Day 1) up to 30 days after the last study drug administration, approximately 120 weeks)
- Duration of Response (DOR)(Tumor assessments performed at Baseline (Day 1), then every 6 weeks (±7 days) thereafter, approximately 88.1 weeks)
- Progression-free Survival (PFS)(Tumor assessments performed at Baseline (Day 1), then every 6 weeks (±7 days) thereafter, approximately 88.1 weeks)
- Disease Control Rate (DCR)(Tumor assessments performed at Baseline (Day 1), then every 6 weeks (±7 days) thereafter, approximately 88.1 weeks)
- Individual Observed Predose Concentrations (Ctrough) of Tusamitamab Ravtansine(Pre-infusion on Cycle 2 Day 1)
- Individual Observed Predose Concentrations (Ctrough) of Ramucirumab(Pre-infusion on Cycle 2 Day 1)
- Number of Participants With Antitherapeutic Antibodies (ATAs) Against Tusamitamab Ravtansine(Upto 92.1 weeks)