Safety Study of Bintrafusp Alfa in Combination With Other Anti-cancer Therapies in Participants With Locally Advanced or Advanced Cervical Cancer (INTR@PID 046)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 13
- 主要终点
- Number of Participants With Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
This study was to evaluate the safety and tolerability of bintrafusp alfa in combination with other anti-cancer therapies in participants with locally advanced or advanced cervical cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- Female
- 接受健康志愿者
- 否
入选标准
- •Inclusion Criteria for participants enrolling into Cohort 1:
- •Study participants had documented persistent, recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix
- •Study participants had not been treated with systemic chemotherapy and were not amenable to curative treatment
- •Prior radiation with or without radio-sensitizing chemotherapy was allowed
- •Inclusion Criteria for participants enrolling into Cohort 2:
- •Participants had documented evidence of cervical adenocarcinoma, squamous cell carcinoma, or adenosquamous carcinoma International Federation of Gynecology and Obstetrics (FIGO) 2018 Stages 1B2 to 4A
- •Participants had not received prior chemotherapy or radiotherapy for cervical cancer
- •Inclusion Criteria for all participants:
- •Archival tumor tissue sample or newly obtained core or excisional biopsy was required
- •Participants who had Eastern Cooperative Oncology Group (ECOG) Performance status (PS) of 0 to 1 were eligible
- •Participants had a life expectancy greater than or equal to 12 weeks
- •Participants had adequate hematological, hepatic, renal, and coagulation function as defined in the protocol
- •Participants with known Human immunodeficiency virus (HIV) infections were eligible if the criteria described in the protocol were met
- •Participants with Hepatitis B virus (HBV) and/or Hepatitis C virus (HCV) infections were eligible if the criteria described in the protocol were met
- •Other protocol defined inclusion criteria could apply
排除标准
- •Exclusion Criteria for All Participants were:
- •Participants with active central nervous system (CNS) metastases causing clinical symptoms or metastases that required therapeutic intervention were excluded. Participants with a history of treated CNS metastases (by surgery or radiation therapy) were not eligible unless they had fully recovered from treatment, demonstrated no progression for at least 4 weeks, and were not using steroids for at least 7 days prior to the start of study intervention
- •Participants that received any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that did not require immuno-suppression
- •Participants with significant acute or chronic infections
- •Participants with active autoimmune disease that might have deteriorated when receiving an immuno-stimulatory agent
- •Participants with clinically significant cardiovascular/cerebrovascular disease including: a cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure, or serious cardiac arrhythmia
- •Participants with a history of bleeding diathesis or recent major bleeding events
- •Participant that had received prior cancer treatment with any other immunotherapy or checkpoint inhibitors or any other immune-modulating monoclonal antibody (mAb)
- •Exclusion Criteria for Participants in Cohort 1A related to use of bevacizumab were:
- •Participants with inadequately controlled hypertension
- •Prior history of hypertensive crisis or hypertensive encephalopathy
- •Participants with significant vascular disease within 6 months prior to Screening
- •Participants with a history of hemoptysis within 1 month prior to Screening
- •Current use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes
- •Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to the first dose of bevacizumab
- •Participants with a history of abdominal or trache-oesophageal fistula or gastrointestinal (GI) perforation within 6 months prior to Screening
- •Participants with clinical signs of GI obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding
- •Participants with evidence of abdominal free air not explained by paracentesis or recent surgical procedure
- •Participants with serious, non-healing wound, active ulcer, or untreated bone fracture
- •Participants with proteinuria
- •Other protocol defined exclusion criteria could apply
研究组 & 干预措施
Cohort 1A:M7824+Cisplatin/Carboplatin+Paclitaxel+Bevacizumab
干预措施: M7824 (Drug)
Cohort 1A:M7824+Cisplatin/Carboplatin+Paclitaxel+Bevacizumab
干预措施: Carboplatin (Drug)
Cohort 1A:M7824+Cisplatin/Carboplatin+Paclitaxel+Bevacizumab
干预措施: Paclitaxel (Drug)
Cohort 1A:M7824+Cisplatin/Carboplatin+Paclitaxel+Bevacizumab
干预措施: Bevacizumab (Drug)
Cohort 1A:M7824+Cisplatin/Carboplatin+Paclitaxel+Bevacizumab
干预措施: Cisplatin (Drug)
Cohort1B:M7824+Cisplatin or Carboplatin+Paclitaxel
干预措施: M7824 (Drug)
Cohort1B:M7824+Cisplatin or Carboplatin+Paclitaxel
干预措施: Carboplatin (Drug)
Cohort1B:M7824+Cisplatin or Carboplatin+Paclitaxel
干预措施: Paclitaxel (Drug)
Cohort1B:M7824+Cisplatin or Carboplatin+Paclitaxel
干预措施: Cisplatin (Drug)
Cohort 2: M7824+Cisplatin+ Radiotherapy
干预措施: M7824 (Drug)
Cohort 2: M7824+Cisplatin+ Radiotherapy
干预措施: Cisplatin (Drug)
Cohort 2: M7824+Cisplatin+ Radiotherapy
干预措施: Radiotherapy (Radiation)
结局指标
主要结局
Number of Participants With Dose-Limiting Toxicities (DLTs)
时间窗: Up to 4 weeks after first administration of study intervention
DLT was defined as Adverse Events (AEs) with any of following toxicities: Grade 4 nonhematologic toxicity or hematologic toxicity lasting more than equal to (\>=) 7 days despite medical intervention; Grade 3 nausea, vomiting, and diarrhea lasting \>= 3 days despite supportive care; Any Grade 3 or Grade 4 nonhematologic lab value leading to hospitalization or persisting for \>= 7 days; Grade 3 or Grade 4: grade 3 is defined as absolute neutrophil count (ANC) less than (\<) 1,000/mm3 with a temperature of \> 38.3 degree Celsius (°C); grade 4 is defined as ANC \< 1,000/mm3 with a temperature of \> 38.3°C, with life-threatening consequences; Thrombocytopenia \< 25,000/mm3 associated with bleeding not resulting in hemodynamic instability or a life-threatening bleeding resulting in urgent intervention; Bleeding events \>= Grade 3 occurring within 5 days of bintrafusp alfa treatment; Prolonged delay (\> 3 weeks) in initiating Cycle 2 due to treatment-related toxicity; Grade 5 toxicity.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: Time from first treatment assessed up to approximately 20 months
Adverse Event (AE) was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. Treatment-Emergent Adverse Events (TEAEs) were defined as events with onset date or worsening during the on-treatment period. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs included serious TEAEs and non-serious TEAEs.
次要结局
- Area Under the Serum Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Bintrafusp Alfa(Pre-dose Up to 20 months)
- Number of Participants With Positive Anti-Drug Antibody (ADA) of Bintrafusp Alfa(Pre-dose Up to 20 months)
- Number of Japanese Participants With Dose-Limiting Toxicities (DLTs)(Up to 4 weeks after first administration of study intervention)
- Number of Japanese Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(Time from first treatment assessed up to approximately 20 months)
- Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Bintrafusp Alfa(Pre-dose Up to 20 months)
- Serum Trough Concentration Levels (Ctrough) of Bintrafusp Alfa(Pre-dose Up to 20 months)
- Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Bintrafusp Alfa(Pre-dose Up to 20 months)
- Time to Reach Maximum Serum Concentration (Tmax) of Bintrafusp Alfa(Pre-dose Up to 20 months)
- Maximum Observed Serum Concentration (Cmax) of Bintrafusp Alfa(Pre-dose Up to 20 months)
- Terminal Elimination Half-Life (T1/2) of Bintrafusp Alfa(Pre-dose Up to 20 months)