A Phase III, Open-label, Multicenter Trial of Avelumab (MSB0010718C) Versus Platinum-based Doublet as a First-line Treatment of Recurrent or Stage IV PD-L1+NSCLC
Overview
- Phase
- Phase 3
- Intervention
- Avelumab
- Conditions
- First Line Non-Small Cell Lung Cancer
- Sponsor
- EMD Serono Research & Development Institute, Inc.
- Enrollment
- 1214
- Locations
- 347
- Primary Endpoint
- Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Independent Review Committee (IRC) in High Programmed Death Ligand 1 (PD-L1) + Full Analysis Set (FAS)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The purpose of this study was to demonstrate superiority with regard to Overall Survival (OS) or Progression Free Survival (PFS) of avelumab versus platinum-based doublet, based on an Independent Review Committee assessment, in Non-small cell lung cancer (NSCLC) participants with Programmed death ligand 1+ (PD-L1+) tumors.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female subjects aged greater than or equal to (\>=) 18 years
- •With Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at trial entry
- •At least 1 measurable tumor lesion
- •With histologically confirmed metastatic or recurrent (Stage IV) non-small cell lung cancer (NSCLC)
- •With availability of a recently-obtained, formalin-fixed, paraffin-embedded (FFPE) tissue sample containing tumor (biopsy from a non-irradiated area preferably within 6 months) or a minimum number of 10 (preferably 25) unstained tumor slides cut within 1 week, and suitable for PD-L1 expression assessment
- •Subjects must not have received any treatment for systemic lung cancer, and have an estimated life expectancy of more than 12 weeks
- •Other protocol defined criteria could apply
Exclusion Criteria
- •Subjects whose disease harbors a EGFR mutation, or anaplastic lymphoma kinase (ALK) rearrangement are not eligible.
- •Other exclusion criteria include prior therapy with any antibody or drug targeting T cell coregulatory proteins, concurrent anticancer treatment, or immunosuppressive agents
- •Known severe hypersensitivity reactions to monoclonal antibodies (Grade \>= 3 NCI CTCAE v 4.03), history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma), and persisting toxicity related to prior therapy of Grade \> 1 NCI-CTCAE v 4.
- •Subjects with brain metastases are excluded, except those meeting the following criteria: brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to randomization, subjects must be either off steroids or on a stable or decreasing dose of \<= 10 mg daily prednisone (or equivalent), and do not have ongoing neurological symptoms that are related to the brain localization of the disease.
- •Other protocol defined criteria could apply
Arms & Interventions
Avelumab Biweekly
Intervention: Avelumab
Avelumab Weekly
Intervention: Cisplatin
Avelumab Weekly
Intervention: Avelumab Weekly
Chemotherapy
Intervention: Pemetrexed
Chemotherapy
Intervention: Paclitaxel
Chemotherapy
Intervention: Gemcitabine
Chemotherapy
Intervention: Carboplatin
Outcomes
Primary Outcomes
Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Independent Review Committee (IRC) in High Programmed Death Ligand 1 (PD-L1) + Full Analysis Set (FAS)
Time Frame: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)
PFS is defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was measured using Kaplan-Meier (KM) estimates.
Overall Survival (OS) in High Programmed Death Ligand 1 (PD-L1) + Full Analysis Set (FAS)
Time Frame: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)
OS is defined as the time from randomization to the date of death, regardless of the actual cause of the participant's death. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier (KM) estimates.
Overall Survival (OS) in High Programmed Death Ligand 1 (PD-L1)+ Modified Full Analysis Set (mFAS)
Time Frame: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)
OS is defined as the time from randomization to the date of death, regardless of the actual cause of the participant's death. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier (KM) estimates.
Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Independent Review Committee (IRC) in High Programmed Death Ligand 1 (PD-L1) + Modified Full Analysis Set (mFAS)
Time Frame: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)
PFS is defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was measured using Kaplan-Meier (KM) estimates.
Secondary Outcomes
- Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Independent Review Committee (IRC) in Moderate and High Programmed Death Ligand 1 (PD-L1)+ Full Analysis Set (FAS)(Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months))
- Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Independent Review Committee (IRC) in Moderate and High Programmed Death Ligand 1 (PD-L1)+ Modified Full Analysis Set (mFAS)(Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months))
- Overall Survival (OS) in Moderate and High Programmed Death Ligand 1 (PD-L1)+ Full Analysis Set (FAS)(Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months))
- Overall Survival (OS) in Moderate and High Programmed Death Ligand 1 (PD-L1)+ Modified Full Analysis Set (mFAS)(Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months))
- Overall Survival (OS) in Full Analysis Set (FAS)(Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months))
- Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) in Moderate and High PD-L1+ Modified Full Analysis Set(Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months))
- Number of Participants With Maximal On-Treatment Changes From Baseline in Vital Signs - Maximal Heart Rate Increase/Decrease(Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months))
- Overall Survival (OS) in Modified Full Analysis Set (mFAS)(Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months))
- Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) in High PD-L1+ Modified Full Analysis Set(Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months))
- Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) in Moderate and High PD-L1+ Full Analysis Set(Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months))
- Number of Participants With Maximal On-Treatment Changes From Baseline in Vital Signs - Maximal Body Temperature Increase(Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months))
- Number of Participants With Maximal On-Treatment Changes From Baseline in Vital Signs - Maximal Weight Increase/Decrease(Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months))
- Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) in High PD-L1+ Full Analysis Set(Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months))
- Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) in High Programmed Death Ligand 1 (PD-L1)+ Full Analysis Set (FAS)(Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months))
- Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) at End of Treatment (EOT) in High Programmed Death Ligand 1 (PD-L1)+ Modified HRQoL Analysis Set(Baseline, End of treatment (up to Week 283.9))
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and AEs of Special Interest (AESIs)(Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months))
- Number of Participants With Shift From Baseline to Greater Than or Equal to (>=) Grade 3 in Laboratory Parameter Values Based on National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03(Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months))
- Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) in High Programmed Death Ligand 1 (PD-L1)+ Modified Full Analysis Set (mFAS)(Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months))
- Change From Baseline in European Quality Of Life 5-dimensions (EQ-5D-5L) Visual Analog Scale (VAS) in High PD-L1+ Health-related Quality of Life (HRQoL) Analysis Set at End of Treatment(Baseline, End of treatment (up to Week 283.9))
- Change From Baseline in European Quality Of Life 5-dimensions (EQ-5D-5L) Visual Analog Scale (VAS) in High Programmed Death Ligand 1 (PD-L1)+ Modified HRQoL Analysis Set(Baseline, End of treatment (Week 283.9))
- Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status at End of Treatment (EOT) in High Programmed Death Ligand 1 (PD-L1)+ HRQoL Analysis Set(Baseline, End of treatment (up to Week 283.9))
- Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status at End of Treatment (EOT) in High Programmed Death Ligand 1 (PD-L1)+ Modified HRQoL Analysis Set(Baseline, End of treatment (Week 283.9))
- Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) at End of Treatment (EOT) in High Programmed Death Ligand 1 (PD-L1)+ HRQoL Analysis Set(Baseline, End of treatment (up to Week 283.9))
- Number of Participants With Maximal On-Treatment Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease(Time from date of randomization up to data cutoff (assessed up to 71.5 months))
- Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Electrocardiogram (ECG) Parameters(Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months))
- Number of Participants With Maximal On-Treatment Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease(Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months))
- Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score(Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months))
- Number of Participants With At Least One Positive Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) for Avelumab(Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months))