A Phase Ib/II, Open-Label Study of M7824 in Combination With Chemotherapy in Participants With Stage IV Non-small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 19
- 主要终点
- Number of Participants With Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
The main purpose of the study was to evaluate the safety and tolerability of M7824 in combination with chemotherapy.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Participants greater than or equals to (>=) 18 years of age inclusive at the time of signing the informed consent
- •Participants who have histologically confirmed diagnosis of Stage IV NSCLC:
- •Participants in Cohort A, B, and C must not have received prior systemic therapy treatment for their Stage IV NSCLC
- •Participants who had disease progression on previous treatment with Programmed death-ligand 1 (PD- L1) inhibitors in combination with platinum-based chemotherapy are enrolled in Cohort D, as long as therapy was completed at least 28 days of the first study intervention.
- •Have measurable disease based on Response evaluation criteria in solid tumors (RECIST) 1.1
- •Have a life expectancy of at least 3 months
- •Availability of archived tumor material (less than [<] 6 months old) adequate for biomarker analysis is mandatory at Screening, central laboratory confirmation is required. Fresh biopsies should be collected if archived tumor material is not available
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at study entry and date of first dose
排除标准
- •The participant's tumor harbors an epidermal growth factor receptor (EGFR) sensitizing (activating) mutation,ROS1 rearrangement, or BRAF V600E mutation or anaplastic lymphoma kinase (ALK) positive, if targeted therapy is locally approved
- •Mixed small cell with NSCLC cancer histology
- •Has received major surgery within 4 weeks prior to the first dose of study intervention; received thoracic radiation therapy (RT) of > 30 gray (Gy) within 6 months prior to the first dose of study intervention
- •Previous malignant disease (other than the target malignancy to be investigated in this study) within the last 3 years
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are clinically stable for at least 2 weeks after the end of the RT and, have no evidence of new or enlarging brain metastases evaluated by imaging, preferably brain magnetic resonance imaging (MRI)
- •Known severe hypersensitivity to study intervention or any components in their formulations
- •For participants in Cohort A, B and C: Has received prior systemic therapy for Stage IV NSCLC, including anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
- •Unable to tolerate computed tomography (CT) or MRI in the opinion of the Investigator and/or allergy to contrast material.
研究组 & 干预措施
Cohort A: Cisplatin or Carboplatin + Pemetrexed + Bintrafusp alfa
Participants received 2400 miligrams (mg) Bintrafusp alfa along with Cisplatin or Carboplatin, and Pemetrexed every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
干预措施: Cisplatin (Drug)
Cohort A: Cisplatin or Carboplatin + Pemetrexed + Bintrafusp alfa
Participants received 2400 miligrams (mg) Bintrafusp alfa along with Cisplatin or Carboplatin, and Pemetrexed every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
干预措施: Carboplatin (Drug)
Cohort A: Cisplatin or Carboplatin + Pemetrexed + Bintrafusp alfa
Participants received 2400 miligrams (mg) Bintrafusp alfa along with Cisplatin or Carboplatin, and Pemetrexed every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
干预措施: Pemetrexed (Drug)
Cohort A: Cisplatin or Carboplatin + Pemetrexed + Bintrafusp alfa
Participants received 2400 miligrams (mg) Bintrafusp alfa along with Cisplatin or Carboplatin, and Pemetrexed every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
干预措施: M7824 (Drug)
Cohort B: Carboplatin + Paclitaxel or Nab-paclitaxel + Bintrafusp alfa
Participants received 2400 mg Bintrafusp alfa along with Carboplatin, and Paclitaxel or Nab-paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
干预措施: Nab-paclitaxel (Drug)
Cohort B: Carboplatin + Paclitaxel or Nab-paclitaxel + Bintrafusp alfa
Participants received 2400 mg Bintrafusp alfa along with Carboplatin, and Paclitaxel or Nab-paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
干预措施: Carboplatin (Drug)
Cohort B: Carboplatin + Paclitaxel or Nab-paclitaxel + Bintrafusp alfa
Participants received 2400 mg Bintrafusp alfa along with Carboplatin, and Paclitaxel or Nab-paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
干预措施: Bintrafusp alfa (Drug)
Cohort B: Carboplatin + Paclitaxel or Nab-paclitaxel + Bintrafusp alfa
Participants received 2400 mg Bintrafusp alfa along with Carboplatin, and Paclitaxel or Nab-paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
干预措施: Paclitaxel (Drug)
Cohort C: Cisplatin or Carboplatin + Gemcitabine + Bintrafusp alfa
Participants received 2400 mg Bintrafusp alfa along with Cisplatin or Carboplatin, and Gemcitabine every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
干预措施: Cisplatin (Drug)
Cohort C: Cisplatin or Carboplatin + Gemcitabine + Bintrafusp alfa
Participants received 2400 mg Bintrafusp alfa along with Cisplatin or Carboplatin, and Gemcitabine every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
干预措施: Gemcitabine (Drug)
Cohort C: Cisplatin or Carboplatin + Gemcitabine + Bintrafusp alfa
Participants received 2400 mg Bintrafusp alfa along with Cisplatin or Carboplatin, and Gemcitabine every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
干预措施: Carboplatin (Drug)
Cohort C: Cisplatin or Carboplatin + Gemcitabine + Bintrafusp alfa
Participants received 2400 mg Bintrafusp alfa along with Cisplatin or Carboplatin, and Gemcitabine every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
干预措施: Bintrafusp alfa (Drug)
Cohort D: Docetaxel + Bintrafusp alfa
Participants received 2400 mg Bintrafusp alfa along with Docetaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
干预措施: Docetaxel (Drug)
Cohort D: Docetaxel + Bintrafusp alfa
Participants received 2400 mg Bintrafusp alfa along with Docetaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
干预措施: Bintrafusp alfa (Drug)
结局指标
主要结局
Number of Participants With Dose-Limiting Toxicities (DLTs)
时间窗: Day 1 Week 1 up to Week 3
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/Cubic Millimeter(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 TEAEs
时间窗: Time from first treatment assessed up to approximately 26 months
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether considered related to the medicinal product or protocol-specified procedure. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAE was defined as events with onset date or worsening during the on-treatment period. TEAEs included serious TEAEs and non-serious TEAEs.
次要结局
- Maximum Observed Plasma Concentration (Cmax) of Bintrafusp Alfa(Predose, Day 22, Day 43, Day 64 and Day 85)
- Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator (IRC)(Time from first treatment assessed up to approximately 26 months)
- Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator(Time from first administration of study drug until the first documentation of PD or death, assessed up to approximately 26 months)
- Overall Survival (OS)(Time from first treatment assessed up to approximately 26 months)
- Duration of Response (DOR)(Time from first documentation of a confirmed objective response to PD or death due to any cause (assessed up to approximately 26 months))
- Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Bintrafusp Alfa(Predose, Day 22, Day 43, Day 64 and Day 85)
- Serum Trough Concentration Levels (Ctrough) of Bintrafusp Alfa(Predose, Day 22, Day 43, Day 64 and Day 85)
- Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Bintrafusp Alfa(Predose, Day 22, Day 43, Day 64 and Day 85)
- Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Bintrafusp Alfa(Predose, Day 22, Day 43, Day 64 and Day 85)
- Time to Reach Maximum Plasma Concentration (Tmax) of Bintrafusp Alfa(Predose, Day 22, Day 43, Day 64 and Day 85)
- Terminal Elimination Half-Life (T1/2) of Bintrafusp Alfa(Predose, Day 22, Day 43, Day 64 and Day 85)
- Number of Participants With Positive Antidrug Antibodies (ADA)(Time from first treatment assessed up to approximately 26 months)