A Phase 3 interventional study of Avelumab and Pemetrexed in First Line Non-Small Cell Lung Cancer, sponsored by EMD Serono Research & Development Institute, Inc.. Completed at 349 sites in 42 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-01-31.
Sponsored by EMD Serono Research & Development Institute, Inc. · Phase 3, Interventional, and Treatment
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.
6,488 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,632 are open to participants now.
This study's enrollment of 1,214 is above the median of 62 across 5,213 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.
Browse Carcinoma, Non-Small-Cell Lung studies →EMD Serono Research & Development Institute, Inc. is the lead sponsor of 85 studies on the registry; 8 are open to participants now.
Of its 46 completed or terminated interventional studies of FDA-regulated products, 38 (83%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Drug: Avelumab
Drug: Cisplatin · Drug: Avelumab Weekly
Drug: Pemetrexed · Drug: Paclitaxel · Drug: Gemcitabine · Drug: Carboplatin
Participants received Avelumab at a dose of 10 milligrams per kilogram (mg/kg) as a 1-hour (-10/+20 minutes) intravenous (IV) infusion once every 2 weeks until disease progression or unacceptable toxicities.
Also known as: Anti-PD-L1, MSB0010718C
Participants received Pemetrexed 500 milligrams per square meter (mg/m\^2) by IV infusion on Day 1 of 3-Week cycle up to a maximum of 6 cycles of IV injection until disease progression or unacceptable toxicities.
Participants received Paclitaxel 200 mg/m\^2 by IV infusion on Day 1 of 3-Week cycle up to a maximum of 6 cycles of IV injection until disease progression or unacceptable toxicities.
Participants received Gemcitabine 1250 mg/m\^2 on Day 1 and Day 8 by IV infusion in 3-Week cycle up to a maximum of 6 cycles when combined with cisplatin of IV injection until disease progression or unacceptable toxicities.
Participants received Gemcitabine 1000 mg/m\^2 on Day 1 and Day 8 by IV infusion in 3-Week cycle up to a maximum of 6 cycles of IV injection when combined with carboplatin until disease progression or unacceptable toxicities.
Participants received Carboplatin area under concentration curve (AUC) 5 mg/mL\*min in 3-Week cycle up to a maximum of 6 cycles of IV injection when combined with gemcitabine until disease progression or unacceptable toxicities.
Participants received Cisplatin 75 mg/m\^2 by IV infusion in 3-Week cycle up to a maximum of 6 cycles of IV injection until disease progression or unacceptable toxicities.
Carboplatin AUC 6 mg/mL\*min by IV infusion in 3-Week cycle up to a maximum of 6 cycles of IV injection when combined with pemetrexed, or paclitaxel until disease progression or unacceptable toxicities.
Participants received Avelumab at a dose of 10 mg/kg as a 1-hour (-10/+20 minutes) IV infusion every week for 12 consecutive weeks.
Also known as: Anti-PD-L1, MSB0010718C
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)
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.
Time frame: 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 High Programmed Death Ligand 1 (PD-L1) + Modified Full Analysis Set (mFAS)
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.
Time frame: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)
Overall Survival (OS) in High Programmed Death Ligand 1 (PD-L1) + Full Analysis Set (FAS)
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.
Time frame: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)
Overall Survival (OS) in High Programmed Death Ligand 1 (PD-L1)+ Modified Full Analysis Set (mFAS)
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.
Time frame: 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)+ Full Analysis Set (FAS)
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.
Time frame: 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)
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.
Time frame: 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)
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.
Time frame: 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)
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.
Time frame: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)
Overall Survival (OS) in Full Analysis Set (FAS)
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.
Time frame: 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)
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.
Time frame: 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
Confirmed objective response was defined as the percentage of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
Time frame: 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
Confirmed objective response was defined as the percentage of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
Time frame: 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
Confirmed objective response was defined as the percentage of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
Time frame: 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
Confirmed objective response was defined as the percentage of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
Time frame: 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)
DOR was defined for participants with confirmed response, as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: 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.
Time frame: 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)
DOR was defined for participants with confirmed response, as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: 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.
Time frame: 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
EQ-5D-5L is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine.
Time frame: 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
EQ-5D-5L is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine.
Time frame: 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
EORTC QLQ-C30 was a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. It consisted of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). The EORTC QLQ-C30 GHS/QoL score ranged from 0 to 100; High score indicated better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL.
Time frame: 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
EORTC QLQ-C30 was a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. It consisted of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). The EORTC QLQ-C30 GHS/QoL score ranged from 0 to 100; High score indicated better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL.
Time frame: 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
EORTC QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The EORTC QLQ-LC13 module generated one multiple-item score assessing dyspnea and a series of single item scores assessing coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arms or shoulder and pain in other parts. Score range: 0 (no burden of symptom domain or single symptom item) to 100 (highest burden of symptoms for symptom domains and single items).
Time frame: 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 Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) at End of Treatment (EOT) in High Programmed Death Ligand 1 (PD-L1)+ Modified HRQoL Analysis Set
EORTC QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The EORTC QLQ-LC13 module generated one multiple-item score assessing dyspnea and a series of single item scores assessing coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arms or shoulder and pain in other parts. Score range: 0 (no burden of symptom domain or single symptom item) to 100 (highest burden of symptoms for symptom domains and single items).
Time frame: Baseline, End of treatment (up to Week 283.9)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and AEs of Special Interest (AESIs)
Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in participant hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAEs were those events with onset dates occurring during the on-treatment period or if the worsening of an event is during the on-treatment period TEAEs included both serious TEAEs and non-serious TEAEs. Any AE that was suspicious to be a potential Immune-related adverse event (irAE) including infusion related reactions were considered AESIs. Number of participants with TEAEs and AESIs were reported.
Time frame: 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
Number of participants with shifts from Baseline values (Grade 0/1/2/3) to abnormal post-baseline values (shift to \>= Grade 4) were reported as per NCI-CTCAE, v4.03 graded from Grade 1 to 5. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death. Shifts in laboratory parameter (anemia, lymphocyte count decreased, neutrophil count decreased, platelet count decreased, white blood cell count decreased, alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatine phosphokinase increased, creatinine increased and Hyperglycemia) were reported.
Time frame: 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
The number of participants with changes from baseline in increased Body Temperature (degree Celsius \[°C\]) were reported by using criteria: Baseline temperature (temp.) less than (\<) 37°C, on treatment change \<1°C, 1 - \<2°C, 2 - \<3°C, greater than or equal to (\>=)3°C and missing; Baseline temp. 37 - \<38°C, on treatment change \<1°C, 1 - \<2°C, 2 - \<3°C, \>=3°C and missing; Baseline temp. 38 - \<39°C, on treatment change \<1°C, 1 - \<2°C, 2 - \<3°C, \>=3°C and missing; Baseline temp. 39-\<40°C, on treatment change \<1°C, 1 - \<2°C, 2 - \<3°C, \>=3°C and missing; Baseline temp. \>=40°C, on treatment change \<1°C, 1 - \<2°C, 2 - \<3°C, \>=3°C and missing; Baseline temp. missing, on treatment change missing.
Time frame: 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
The number of participants with maximal on-treatment changes from baseline in Increase (Ic.)/Decrease (Dc.) in maximal weight were reported by using criteria: Ic./Dc. From baseline, on treatment (TR) change \<10 percentage (%), \>=10% and missing.
Time frame: 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
The number of participants with maximal on-treatment (TR) changes from baseline (BS) in Increase (Ic.)/Decrease (Dc.) heart rate (HR) (beats per minute \[bpm\]) were reported by using criteria: Ic./Dc. BS HR \<100/\>=100 bpm, on treatment change =\<20 bpm, \>20 - =\<40 bpm, \>40 bpm and missing; Ic./Dc. BS HR missing, on treatment change missing.
Time frame: 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
The number of participants with maximal on-treatment changes from baseline (BS) in Increase (Ic.)/Decrease (Dc.) Systolic Blood Pressure (SBP) and diastolic blood pressure (DBP) (millimeter of mercury \[mmHg\]) were reported by using criteria: Ic./Dc. BS SBP \<140 mmHg and \>=140 mmHg, on maximal treatment (TR) change =\<20 mmHg, \>20 - =\<40 mmHg, \>40 mmHg and missing; Ic./Dc. BS SBP missing, on maximal treatment (TR) change missing; Ic./Dc. BS DBP \<90 mmHg and \>= 90 mmHg, on maximal TR change =\<20 mmHg, \>20 - =\<40 mmHg, \>40 mmHg and missing; Ic./Dc. BS DBP missing on maximal TR change missing.
Time frame: 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 Respiration Rate Increase/Decrease
The number of participants with maximal on-treatment (TR) changes from baseline (BS) in Increase (Ic.)/Decrease (Dc.) maximal Respiration Rate (RR) were reported by using criteria: Ic./Dc. BS RR \<20 breaths per minute (breaths/min), on TR change =\<5 breaths/min, \>5 - =\<10 breaths/min, \>10 breaths/min and missing. Ic./Dc. BS RR missing, on TR change missing. Ic./Dc. BS RR \>=20 breaths/min, on TR change =\<5 breaths/min, \>5 - =\<10 breaths/min, \>10 breaths/min and missing.
Time frame: 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
ECG parameters included heart rate, PR interval, QRS interval, corrected QT interval using Bazett's formula (QTcB) and corrected QT interval using Fridericia's formula (QTcF). PCSA criteria for abnormal value of ECG parameters: any heart rate \<= 50 bpm and decrease from baseline \>=20 bpm , any hear rate \>= 120 bpm and increase from baseline \>= 20 bpm; PR interval: \>= 220 milliseconds (ms) and increase from baseline \>= 20 ms; QRS interval \>= 120 ms; QTcF \> 450 ms, \> 480 ms, \> 500 ms, QTcF increase from baseline \> 30 ms and QTcF increase from baseline \> 60 ms; QTcB \> 450 ms, \> 480 ms, \> 500 ms, QTcB increase from baseline \> 30 ms and QTcB increase from baseline \> 60 ms.
Time frame: 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
ECOG performance status measured to assess participant's performance status on a scale of 0 to 5, where 0 = Fully active, able to carry on all pre-disease activities without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities; 3 = Capable of only limited self-care, confined to bed/chair for more than 50 percent of waking hours; 4 = Completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5 = dead. ECOG performance status was reported in terms of number of participants with baseline value vs worst post-baseline value (that is \[i.e.\] highest score).
Time frame: 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
Serum samples were analyzed by a validated electrochemiluminesce immunoassay to detect the presence of antidrug antibodies (ADA). Samples that screened positive were subsequently tested in a confirmatory assay were tested for neutralizing antibodies (nAb). Number of participants with ADA or nAb positive results for Avelumab were reported.
Time frame: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)
| Milestone | Avelumab Biweekly | Avelumab Weekly | Chemotherapy |
|---|---|---|---|
| Started | 366 | 322 | 526 |
| Completed | 366 | 322 | 526 |
| Not completed | 0 | 0 | 0 |
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.
| months | Avelumab Biweekly | Chemotherapy |
|---|---|---|
| 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) | 8.4 (5.4 to 12.6) | 5.6 (5.4 to 6.8) |
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.
| months | Avelumab Weekly | Chemotherapy |
|---|---|---|
| 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) | 7.5 (4.2 to 11.1) | 5.6 (5.0 to 6.8) |
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.
| months | Avelumab Biweekly | Chemotherapy |
|---|---|---|
| Overall Survival (OS) in High Programmed Death Ligand 1 (PD-L1) + Full Analysis Set (FAS) | 20.1 (15.0 to 24.3) | 14.9 (11.8 to 18.6) |
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.
| months | Avelumab Weekly | Chemotherapy |
|---|---|---|
| Overall Survival (OS) in High Programmed Death Ligand 1 (PD-L1)+ Modified Full Analysis Set (mFAS) | 19.3 (14.0 to 28.1) | 15.3 (11.6 to 19.1) |
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.
| months | Avelumab Biweekly | Chemotherapy |
|---|---|---|
| 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) | 6.9 (5.4 to 9.6) | 5.6 (5.5 to 6.6) |
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.
| months | Avelumab Weekly | Chemotherapy |
|---|---|---|
| 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) | 5.6 (2.8 to 8.2) | 5.6 (5.5 to 6.6) |
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.
| months | Avelumab Biweekly | Chemotherapy |
|---|---|---|
| Overall Survival (OS) in Moderate and High Programmed Death Ligand 1 (PD-L1)+ Full Analysis Set (FAS) | 18.7 (14.6 to 21.7) | 13.3 (11.4 to 16.6) |
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.
| months | Avelumab Weekly | Chemotherapy |
|---|---|---|
| Overall Survival (OS) in Moderate and High Programmed Death Ligand 1 (PD-L1)+ Modified Full Analysis Set (mFAS) | 16.8 (12.5 to 21.3) | 13.0 (11.1 to 17.0) |
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.
| months | Avelumab Biweekly | Chemotherapy |
|---|---|---|
| Overall Survival (OS) in Full Analysis Set (FAS) | 15.0 (12.5 to 19.1) | 14.3 (11.8 to 15.6) |
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.
| months | Avelumab Weekly | Chemotherapy |
|---|---|---|
| Overall Survival (OS) in Modified Full Analysis Set (mFAS) | 15.4 (12.1 to 18.1) | 14.8 (11.6 to 16.4) |
Confirmed objective response was defined as the percentage of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
| percentage of participants | Avelumab Biweekly | Chemotherapy |
|---|---|---|
| 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 | 37.7 (30.0 to 46.0) | 30.1 (24.1 to 36.7) |
Confirmed objective response was defined as the percentage of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
| percentage of participants | Avelumab Weekly | Chemotherapy |
|---|---|---|
| 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 | 34.6 (26.5 to 43.5) | 30.2 (22.5 to 38.9) |
Confirmed objective response was defined as the percentage of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
| percentage of participants | Avelumab Biweekly | Chemotherapy |
|---|---|---|
| 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 | 33.5 (27.3 to 40.2) | 30.3 (25.1 to 35.8) |
Confirmed objective response was defined as the percentage of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
| percentage of participants | Avelumab Weekly | Chemotherapy |
|---|---|---|
| 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 | 30.6 (24.0 to 37.8) | 30.6 (24.0 to 37.8) |
DOR was defined for participants with confirmed response, as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: 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.
| months | Avelumab Biweekly | Chemotherapy |
|---|---|---|
| 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) | 35.9 (1.4 to 60.8) | 8.4 (1.0 to 63.9) |
DOR was defined for participants with confirmed response, as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: 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.
| months | Avelumab Weekly | Chemotherapy |
|---|---|---|
| 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) | 19.4 (3.8 to 43.9) | 8.4 (1.0 to 35.9) |
EQ-5D-5L is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine.
| millimeter (mm) | Avelumab Biweekly | Chemotherapy |
|---|---|---|
| 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 | -6.2 ± 23.61 | -5.2 ± 20.48 |
EQ-5D-5L is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine.
| millimeter | Avelumab Weekly | Chemotherapy |
|---|---|---|
| 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 | -10.3 ± 22.49 | -3.9 ± 20.21 |
EORTC QLQ-C30 was a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. It consisted of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). The EORTC QLQ-C30 GHS/QoL score ranged from 0 to 100; High score indicated better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL.
| score on a scale | Avelumab Biweekly | Chemotherapy |
|---|---|---|
| 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 | -0.3 ± 22.30 | -6.1 ± 24.55 |
EORTC QLQ-C30 was a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. It consisted of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). The EORTC QLQ-C30 GHS/QoL score ranged from 0 to 100; High score indicated better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL.
| score on a scale | Avelumab Weekly | Chemotherapy |
|---|---|---|
| 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 | -12.9 ± 21.03 | -4.5 ± 23.30 |
EORTC QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The EORTC QLQ-LC13 module generated one multiple-item score assessing dyspnea and a series of single item scores assessing coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arms or shoulder and pain in other parts. Score range: 0 (no burden of symptom domain or single symptom item) to 100 (highest burden of symptoms for symptom domains and single items).
| score on a scale | Avelumab Biweekly | Chemotherapy |
|---|---|---|
| Dyspnea | 7.3 ± 24.10 | 5.2 ± 19.66 |
| Coughing | 2.4 ± 29.04 | -4.3 ± 27.01 |
| Hemoptysis | -1.8 ± 21.48 | 1.5 ± 13.95 |
| Sore mouth | 3.0 ± 18.28 | 1.9 ± 21.77 |
| Dysphagia | 3.0 ± 19.36 | -0.6 ± 21.36 |
| Peripheral neuropathy | 3.6 ± 17.60 | 10.8 ± 24.46 |
| Alopecia | 0.0 ± 8.98 | 14.2 ± 32.93 |
| Pain in chest | -4.2 ± 22.96 | -1.5 ± 26.33 |
| Pain in arm or shoulder | 0.6 ± 32.71 | 1.9 ± 26.50 |
| Pain in other parts | 1.8 ± 33.29 | 1.5 ± 30.36 |
EORTC QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The EORTC QLQ-LC13 module generated one multiple-item score assessing dyspnea and a series of single item scores assessing coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arms or shoulder and pain in other parts. Score range: 0 (no burden of symptom domain or single symptom item) to 100 (highest burden of symptoms for symptom domains and single items).
| score on a scale | Avelumab Weekly | Chemotherapy |
|---|---|---|
| Dyspnea | 6.1 ± 27.19 | 4.9 ± 18.77 |
| Coughing | -0.6 ± 28.87 | -5.2 ± 24.34 |
| Hemoptysis | -0.6 ± 17.89 | 0.0 ± 12.59 |
| Sore mouth | 0.6 ± 13.97 | 1.9 ± 17.71 |
| Dysphagia | 3.8 ± 14.10 | -0.5 ± 22.88 |
| Peripheral neuropathy | 0.6 ± 21.17 | 9.9 ± 23.49 |
| Alopecia | -2.5 ± 17.11 | 15.0 ± 29.70 |
| Pain in chest | 2.5 ± 29.13 | -0.5 ± 25.50 |
| Pain in arm or shoulder | 4.4 ± 30.69 | 1.4 ± 25.46 |
| Pain in other parts | 10.1 ± 28.93 | 1.4 ± 28.97 |
Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in participant hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAEs were those events with onset dates occurring during the on-treatment period or if the worsening of an event is during the on-treatment period TEAEs included both serious TEAEs and non-serious TEAEs. Any AE that was suspicious to be a potential Immune-related adverse event (irAE) including infusion related reactions were considered AESIs. Number of participants with TEAEs and AESIs were reported.
| Participants | Avelumab Biweekly | Avelumab Weekly | Chemotherapy |
|---|---|---|---|
| TEAEs | 346 | 308 | 484 |
| AESIs | 158 | 160 | 173 |
Number of participants with shifts from Baseline values (Grade 0/1/2/3) to abnormal post-baseline values (shift to \>= Grade 4) were reported as per NCI-CTCAE, v4.03 graded from Grade 1 to 5. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death. Shifts in laboratory parameter (anemia, lymphocyte count decreased, neutrophil count decreased, platelet count decreased, white blood cell count decreased, alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatine phosphokinase increased, creatinine increased and Hyperglycemia) were reported.
| Participants | Avelumab Biweekly | Avelumab Weekly | Chemotherapy |
|---|---|---|---|
| Anemia: Grade 0 to Grade 3 | 4 | 2 | 58 |
| Anemia: Grade 1 to Grade 3 | 4 | 5 | 30 |
| Anemia: Grade 2 to Grade 3 | 4 | 6 | 6 |
| Lymphocyte count decreased: Grade 0 to Grade 3 | 16 | 15 | 31 |
| Lymphocyte count decreased: Grade 0 to Grade 4 | 1 | 2 | 3 |
| Lymphocyte count decreased: Grade 1 to Grade 3 | 2 | 10 | 12 |
| Lymphocyte count decreased: Grade 2 to Grade 3 | 7 | 6 | 12 |
| Lymphocyte count decreased: Grade 2 to Grade 4 | 0 | 0 | 1 |
| Lymphocyte count decreased: Grade 3 to Grade 4 | 0 | 0 | 1 |
| Neutrophil count decreased: Grade 0 to Grade 3 | 4 | 4 | 65 |
| Neutrophil count decreased: Grade 0 to Grade 4 | 0 | 3 | 25 |
| Neutrophil count decreased: Grade 1 to Grade 3 | 1 | 0 | 1 |
| Platelet count decreased: Grade 0 to Grade 3 | 0 | 1 | 18 |
| Platelet count decreased: Grade 0 to Grade 4 | 0 | 3 | 20 |
| Platelet count decreased: Grade 1 to Grade 3 | 0 | 1 | 0 |
| White blood cell count decreased: Grade 0 to Grade 3 | 0 | 3 | 24 |
| White blood cell count decreased: Grade 0 to Grade 4 | 0 | 1 | 11 |
| Alanine aminotransferase increased: Grade 0 to Grade 3 | 12 | 8 | 5 |
| Alanine aminotransferase increased: Grade 0 to Grade 4 | 1 | 1 | 3 |
| Alanine aminotransferase increased: Grade 1 to Grade 3 | 1 | 0 | 2 |
| Alkaline phosphatase increased: Grade 0 to Grade 3 | 0 | 3 | 1 |
| Alkaline phosphatase increased: Grade 1 to Grade 3 | 1 | 3 | 1 |
| Alkaline phosphatase increased: Grade 1 to Grade 4 | 0 | 0 | 1 |
| Alkaline phosphatase increased: Grade 2 to Grade 3 | 0 | 1 | 0 |
| Aspartate aminotransferase increased: Grade 0 to Grade 3 | 7 | 4 | 3 |
| Aspartate aminotransferase increased: Grade 0 to Grade 4 | 1 | 2 | 2 |
| Aspartate aminotransferase increased: Grade 1 to Grade 3 | 0 | 0 | 1 |
| Blood bilirubin increased: Grade 0 to Grade 3 | 0 | 4 | 3 |
| Blood bilirubin increased: Grade 0 to Grade 4 | 0 | 1 | 0 |
| Creatine phosphokinase increased: Grade 0 to Grade 3 | 6 | 5 | 1 |
| Creatine phosphokinase increased: Grade 0 to Grade 4 | 5 | 0 | 0 |
| Creatine phosphokinase increased: Grade 1 to Grade 4 | 0 | 1 | 0 |
| Creatine phosphokinase increased: Grade 2 to Grade 3 | 0 | 1 | 0 |
| Creatinine increased: Grade 0 to Grade 3 | 6 | 4 | 4 |
| Creatinine increased: Grade 1 to Grade 3 | 0 | 0 | 1 |
| Hyperglycemia: Grade 0 to Grade 3 | 21 | 20 | 35 |
| Hyperglycemia: Grade 0 to Grade 4 | 0 | 0 | 3 |
The number of participants with changes from baseline in increased Body Temperature (degree Celsius \[°C\]) were reported by using criteria: Baseline temperature (temp.) less than (\<) 37°C, on treatment change \<1°C, 1 - \<2°C, 2 - \<3°C, greater than or equal to (\>=)3°C and missing; Baseline temp. 37 - \<38°C, on treatment change \<1°C, 1 - \<2°C, 2 - \<3°C, \>=3°C and missing; Baseline temp. 38 - \<39°C, on treatment change \<1°C, 1 - \<2°C, 2 - \<3°C, \>=3°C and missing; Baseline temp. 39-\<40°C, on treatment change \<1°C, 1 - \<2°C, 2 - \<3°C, \>=3°C and missing; Baseline temp. \>=40°C, on treatment change \<1°C, 1 - \<2°C, 2 - \<3°C, \>=3°C and missing; Baseline temp. missing, on treatment change missing.
| Participants | Avelumab Biweekly | Avelumab Weekly | Chemotherapy |
|---|---|---|---|
| Baseline temp. <37°C, on treatment change <1°C | 271 | 256 | 403 |
| Baseline temp.<37°C, on treatment change 1 - <2°C | 45 | 32 | 33 |
| Baseline temp. <37°C, on treatment change 2 - <3°C | 3 | 2 | 0 |
| Baseline temp. <37°C, on treatment change >=3°C | 0 | 1 | 0 |
| Baseline temp. <37°C, on treatment change missing | 16 | 6 | 21 |
| Baseline temp. 37 - <38°C, on treatment change <1°C | 23 | 19 | 37 |
| Baseline temp. 37 - <38°C, on treatment change 1 - <2°C | 1 | 2 | 1 |
| Baseline temp. 37 - <38°C, on treatment change 2 - <3°C | 0 | 0 | 0 |
| Baseline temp. 37 - <38°C, on treatment change >=3°C | 0 | 0 | 0 |
| Baseline temp. 37 - <38°C, on treatment change missing | 1 | 0 | 3 |
| Baseline temp. 38 - <39°C, on treatment change <1°C | 0 | 0 | 0 |
| Baseline temp. 38 - <39°C, on treatment change 1 - <2°C | 0 | 0 | 0 |
| Baseline temp. 38 - <39°C, on treatment change 2 - <3°C | 0 | 0 | 0 |
| Baseline temp. 38 - <39°C, on treatment change >=3°C | 0 | 0 | 0 |
| Baseline temp. 38 - <39°C, on treatment change missing | 0 | 0 | 0 |
| Baseline temp. 39 - <40°C, on treatment change <1°C | 1 | 0 | 0 |
| Baseline temp. 39 - <40°C, on treatment change 1 - <2°C | 0 | 0 | 0 |
| Baseline temp. 39 - <40°C, on treatment change 2 - <3°C | 0 | 0 | 0 |
| Baseline temp. 39 - <40°C, on treatment change >=3°C | 0 | 0 | 0 |
| Baseline temp. 39 - <40°C, on treatment change missing | 0 | 0 | 0 |
| Baseline temp. >=40°C, on treatment change <1°C | 0 | 0 | 0 |
| Baseline temp. >=40°C, on treatment change 1 - <2°C | 0 | 0 | 0 |
| Baseline temp. >=40°C, on treatment change 2 - <3°C | 0 | 0 | 0 |
| Baseline temp. >=40°C, on treatment change >=3°C | 0 | 0 | 0 |
| Baseline temp. >=40°C, on treatment change missing | 0 | 0 | 0 |
| Baseline temp. missing, on treatment change missing | 0 | 0 | 2 |
The number of participants with maximal on-treatment changes from baseline in Increase (Ic.)/Decrease (Dc.) in maximal weight were reported by using criteria: Ic./Dc. From baseline, on treatment (TR) change \<10 percentage (%), \>=10% and missing.
| Participants | Avelumab Biweekly | Avelumab Weekly | Chemotherapy |
|---|---|---|---|
| Ic. from baseline, on TR change <10% | 302 | 280 | 436 |
| Ic. from baseline, on TR change >=10% | 38 | 28 | 39 |
| Ic. from baseline, on TR change missing | 21 | 10 | 25 |
| Dc. from baseline, on TR change <10% | 296 | 258 | 423 |
| Dc. from baseline, on TR change >=10% | 44 | 50 | 52 |
| Dc. from baseline, on TR change missing | 21 | 10 | 25 |
The number of participants with maximal on-treatment (TR) changes from baseline (BS) in Increase (Ic.)/Decrease (Dc.) heart rate (HR) (beats per minute \[bpm\]) were reported by using criteria: Ic./Dc. BS HR \<100/\>=100 bpm, on treatment change =\<20 bpm, \>20 - =\<40 bpm, \>40 bpm and missing; Ic./Dc. BS HR missing, on treatment change missing.
| Participants | Avelumab Biweekly | Avelumab Weekly | Chemotherapy |
|---|---|---|---|
| Ic. BS HR <100 bpm, on TR change =<20 bpm | 206 | 202 | 332 |
| Ic. BS HR <100 bpm, on TR change >20 - =<40 bpm | 86 | 66 | 85 |
| Ic. BS HR <100 bpm, on TR change >40 bpm | 21 | 12 | 9 |
| Ic. BS HR <100 bpm, on TR change missing | 14 | 5 | 16 |
| Ic. BS HR >= 100 bpm, on TR change =<20 bpm | 31 | 30 | 46 |
| Ic. BS HR >= 100 bpm, on TR change >20 - =<40 bpm | 0 | 2 | 3 |
| Ic. BS HR >= 100 bpm, on TR change >40 bpm | 0 | 0 | 0 |
| Ic. BS HR >= 100 bpm, on TR change missing | 3 | 1 | 7 |
| Ic. BS HR missing, on TR change missing | 0 | 0 | 2 |
| Dc. BS HR <100 bpm, on TR change =<20 bpm | 267 | 227 | 385 |
| Dc. BS HR <100 bpm, on TR change >20 - =<40 bpm | 44 | 52 | 40 |
| Dc. BS HR <100 bpm, on TR change >40 bpm | 2 | 1 | 1 |
| Dc. BS HR <100 bpm, on TR change missing | 14 | 5 | 16 |
| Dc. BS HR >= 100 bpm, on TR change =<20 bpm | 14 | 13 | 20 |
| Dc. BS HR >= 100 bpm, on TR change >20 - =<40 bpm | 6 | 12 | 26 |
| Dc. BS HR >= 100 bpm, on TR change >40 bpm | 11 | 7 | 3 |
| Dc. BS HR >= 100 bpm, on TR change missing | 3 | 1 | 7 |
| Dc. BS HR missing, on TR change missing | 0 | 0 | 2 |
The number of participants with maximal on-treatment changes from baseline (BS) in Increase (Ic.)/Decrease (Dc.) Systolic Blood Pressure (SBP) and diastolic blood pressure (DBP) (millimeter of mercury \[mmHg\]) were reported by using criteria: Ic./Dc. BS SBP \<140 mmHg and \>=140 mmHg, on maximal treatment (TR) change =\<20 mmHg, \>20 - =\<40 mmHg, \>40 mmHg and missing; Ic./Dc. BS SBP missing, on maximal treatment (TR) change missing; Ic./Dc. BS DBP \<90 mmHg and \>= 90 mmHg, on maximal TR change =\<20 mmHg, \>20 - =\<40 mmHg, \>40 mmHg and missing; Ic./Dc. BS DBP missing on maximal TR change missing.
| Participants | Avelumab Biweekly | Avelumab Weekly | Chemotherapy |
|---|---|---|---|
| Ic. BS SBP <140 mmHg, on TR change =<20 mmHg | 219 | 209 | 278 |
| Ic. BS SBP <140 mmHg, on TR change >20 - =<40 mmHg | 61 | 56 | 104 |
| Ic. BS SBP <140 mmHg, on TR change >40 mmHg | 16 | 16 | 10 |
| Ic. BS SBP <140 mmHg, on TR change missing | 14 | 4 | 21 |
| Ic. BS SBP >=140 mmHg, on TR change =<20 mmHg | 41 | 26 | 78 |
| Ic. BS SBP >=140 mmHg, on TR change >20 - =<40 mmHg | 7 | 5 | 5 |
| Ic. BS SBP >=140 mmHg, on TR change >40 mmHg | 0 | 0 | 1 |
| Ic. BS SBP > = 140 mmHg, on TR change missing | 3 | 2 | 2 |
| Ic. BS SBP missing, on TR change missing | 0 | 0 | 1 |
| Dc. BS SBP <140 mmHg, on TR change =<20 mmHg | 220 | 204 | 322 |
| Dc. BS SBP <140 mmHg, on TR change >20 - =<40 mmHg | 70 | 70 | 69 |
| Dc. BS SBP <140 mmHg, on TR change >40 mmHg | 6 | 7 | 1 |
| Dc. BS SBP <140 mmHg, on TR change missing | 14 | 4 | 21 |
| Dc. BS SBP >=140 mmHg, on TR change =<20 mmHg | 11 | 6 | 32 |
| Dc. BS SBP >=140 mmHg, on TR change >20 - =<40 mmHg | 25 | 15 | 34 |
| Dc. BS SBP >=140 mmHg, on TR change >40 mmHg | 12 | 10 | 18 |
| Dc. BS SBP > = 140 mmHg, on TR change missing | 3 | 2 | 2 |
| Dc. BS SBP missing, on TR change missing | 0 | 0 | 1 |
| Ic. BS DBP <90 mmHg, on TR change =<20 mmHg | 272 | 260 | 402 |
| Ic. BS DBP <90 mmHg, on TR change >20 - =<40 mmHg | 48 | 37 | 45 |
| Ic. BS DBP <90 mmHg, on TR change >40 mmHg | 0 | 1 | 1 |
| Ic. BS DBP <90 mmHg, on TR change missing | 17 | 5 | 23 |
| Ic. BS DBP missing, on TR change missing | 0 | 0 | 1 |
| Ic. BS DBP >=90 mmHg, on TR change =<20 mmHg | 24 | 12 | 28 |
| Ic. BS DBP >=90 mmHg, on TR change >20 - =<40 mmHg | 0 | 1 | 0 |
| Ic. BS DBP >=90 mmHg, on TR change >40 mmHg | 0 | 1 | 0 |
| Ic. BS DBP >=90 mmHg, on TR change missing | 0 | 1 | 0 |
| Dc. BS DBP <90 mmHg, on TR change =<20 mmHg | 279 | 264 | 415 |
| Dc. BS DBP <90 mmHg, on TR change >20 - =<40 mmHg | 38 | 33 | 32 |
| Dc. BS DBP <90 mmHg, on TR change >40 mmHg | 3 | 1 | 1 |
| Dc. BS DBP <90 mmHg, on TR change missing | 17 | 5 | 23 |
| Dc. BS DBP >=90 mmHg, on TR change =<20 mmHg | 11 | 5 | 18 |
| Dc. BS DBP >=90 mmHg,on TR change >20 - =<40 mmHg | 12 | 9 | 10 |
| Dc. BS DBP >=90 mmHg, on TR change >40 mmHg | 1 | 0 | 0 |
| Dc. BS DBP >=90 mmHg, on TR change missing | 0 | 1 | 0 |
| Dc. BS DBP missing, on TR change missing | 0 | 0 | 1 |
The number of participants with maximal on-treatment (TR) changes from baseline (BS) in Increase (Ic.)/Decrease (Dc.) maximal Respiration Rate (RR) were reported by using criteria: Ic./Dc. BS RR \<20 breaths per minute (breaths/min), on TR change =\<5 breaths/min, \>5 - =\<10 breaths/min, \>10 breaths/min and missing. Ic./Dc. BS RR missing, on TR change missing. Ic./Dc. BS RR \>=20 breaths/min, on TR change =\<5 breaths/min, \>5 - =\<10 breaths/min, \>10 breaths/min and missing.
| Participants | Avelumab Biweekly | Avelumab Weekly | Chemotherapy |
|---|---|---|---|
| Ic. BS RR <20 breaths/min, on TR change =<5 breaths/min | 221 | 224 | 306 |
| Ic.BS RR<20 breaths/min, on TR change >5 - = <10 breaths/min | 18 | 13 | 26 |
| Ic. BS RR <20 breaths/min, on TR change >10 breaths/min | 1 | 1 | 2 |
| Ic. BS RR <20 breaths/min, on TR change missing | 11 | 4 | 14 |
| Ic. BS RR >=20 breaths/min, on TR change =<5 breaths/min | 89 | 68 | 124 |
| Ic.BS RR >=20 breaths/min, on TR change >5 - =<10 breaths/min | 5 | 4 | 2 |
| Ic. BS RR >=20 breaths/min, on TR change >10 breaths/min | 3 | 1 | 0 |
| Ic. BS RR >=20 breaths/min, on TR change missing | 7 | 2 | 15 |
| Ic. BS RR missing, on TR change missing | 6 | 1 | 11 |
| Dc. BS RR <20 breaths/min, on TR change =<5 breaths/min | 232 | 236 | 325 |
| Dc. BS RR <20 breaths/min, on TR change >5 - =<10 breaths/min | 8 | 2 | 8 |
| Dc. BS RR <20 breaths/min, on TR change >10 breaths/min | 0 | 0 | 1 |
| Dc. BS RR <20 breaths/min, on TR change missing | 11 | 4 | 14 |
| Dc. BS RR >=20 breaths/min, on TR ch =<5 breaths/min | 79 | 58 | 101 |
| Dc.BS RR >=20 breaths/min, on TR change >5 - =<10 breaths/min | 14 | 13 | 22 |
| Dc. BS RR >=20 breaths/min, on TR change >10 breaths/min | 4 | 2 | 3 |
| Dc. BS RR >=20 breaths/min, on TR change missing | 7 | 2 | 15 |
| Dc. BS RR missing, on TR change missing | 6 | 1 | 11 |
ECG parameters included heart rate, PR interval, QRS interval, corrected QT interval using Bazett's formula (QTcB) and corrected QT interval using Fridericia's formula (QTcF). PCSA criteria for abnormal value of ECG parameters: any heart rate \<= 50 bpm and decrease from baseline \>=20 bpm , any hear rate \>= 120 bpm and increase from baseline \>= 20 bpm; PR interval: \>= 220 milliseconds (ms) and increase from baseline \>= 20 ms; QRS interval \>= 120 ms; QTcF \> 450 ms, \> 480 ms, \> 500 ms, QTcF increase from baseline \> 30 ms and QTcF increase from baseline \> 60 ms; QTcB \> 450 ms, \> 480 ms, \> 500 ms, QTcB increase from baseline \> 30 ms and QTcB increase from baseline \> 60 ms.
| Participants | Avelumab Biweekly | Avelumab Weekly | Chemotherapy |
|---|---|---|---|
| Heart Rate <= 50 bpm and decrease from baseline >= 20 bpm | 1 | 1 | 0 |
| Heart Rate >= 120 bpm and decrease from baseline >= 20 bpm | 10 | 6 | 7 |
| PR interval >= 220 ms and increase from baseline >= 20 ms | 0 | 5 | 3 |
| QRS interval >= 120 ms | 18 | 10 | 15 |
| QTcF > 450 ms | 19 | 13 | 24 |
| QTcF > 480 ms | 5 | 4 | 11 |
| QTcF > 500 ms | 3 | 1 | 5 |
| QTcF increase from baseline > 30 ms | 20 | 12 | 39 |
| QTcF increase from baseline > 60 ms | 6 | 1 | 13 |
| QTcB > 450 ms | 49 | 31 | 70 |
| QTcB > 480 ms | 13 | 11 | 24 |
| QTcB > 500 ms | 6 | 5 | 16 |
| QTcB increase from baseline > 30 ms | 32 | 25 | 49 |
| QTcB increase from baseline > 60 ms | 11 | 7 | 19 |
ECOG performance status measured to assess participant's performance status on a scale of 0 to 5, where 0 = Fully active, able to carry on all pre-disease activities without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities; 3 = Capable of only limited self-care, confined to bed/chair for more than 50 percent of waking hours; 4 = Completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5 = dead. ECOG performance status was reported in terms of number of participants with baseline value vs worst post-baseline value (that is \[i.e.\] highest score).
| Participants | Avelumab Biweekly | Avelumab Weekly | Chemotherapy |
|---|---|---|---|
| Baseline score 0, worst post-baseline score 0 | 50 | 35 | 84 |
| Baseline score 0, worst post-baseline score 1 | 56 | 49 | 83 |
| Baseline score 0, worst post-baseline score 2 | 8 | 9 | 11 |
| Baseline score 0, worst post-baseline score 3 | 1 | 7 | 4 |
| Baseline score 0, worst post-baseline score 4 | 1 | 0 | 0 |
| Baseline score 0, worst post-baseline score 5 | 0 | 0 | 1 |
| Baseline score 0, worst post-baseline score Missing | 6 | 4 | 4 |
| Baseline score 1, worst post-baseline score 0 | 1 | 2 | 4 |
| Baseline score 1, worst post-baseline score 1 | 168 | 153 | 233 |
| Baseline score 1, worst post-baseline score 2 | 35 | 32 | 46 |
| Baseline score 1, worst post-baseline score 3 | 16 | 18 | 6 |
| Baseline score 1, worst post-baseline score 4 | 3 | 1 | 4 |
| Baseline score 1, worst post-baseline score 5 | 5 | 1 | 3 |
| Baseline score 1, worst post-baseline score Missing | 10 | 6 | 16 |
| Baseline score >=2, worst post-baseline score 0 | 0 | 0 | 0 |
| Baseline score >=2, worst post-baseline score 1 | 0 | 0 | 0 |
| Baseline score >=2, worst post-baseline score 2 | 0 | 0 | 0 |
| Baseline score >=2, worst post-baseline score 3 | 1 | 0 | 0 |
| Baseline score >=2, worst post-baseline score 4 | 0 | 0 | 0 |
| Baseline score >=2, worst post-baseline score 5 | 0 | 1 | 0 |
| Baseline score >=2, worst post-baseline score missing | 0 | 0 | 0 |
| Baseline score missing, worst post-baseline score 0 | 0 | 0 | 0 |
| Baseline score missing, worst post-baseline score 1 | 0 | 0 | 1 |
| Baseline score missing, worst post-baseline score 2 | 0 | 0 | 0 |
| Baseline score missing, worst post-baseline score 3 | 0 | 0 | 0 |
| Baseline score missing, worst post-baseline score 4 | 0 | 0 | 0 |
| Baseline score missing, worst post-baseline score 5 | 0 | 0 | 0 |
| Baseline score missing, worst post-baseline score missing | 0 | 0 | 0 |
Serum samples were analyzed by a validated electrochemiluminesce immunoassay to detect the presence of antidrug antibodies (ADA). Samples that screened positive were subsequently tested in a confirmatory assay were tested for neutralizing antibodies (nAb). Number of participants with ADA or nAb positive results for Avelumab were reported.
| Participants | Avelumab Biweekly | Avelumab Weekly |
|---|---|---|
| ADAs to Avelumab | 66 | 38 |
| NAbs to Avelumab | 43 | 18 |
Collected over Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Avelumab Biweekly | 279/366 (76.2%) | 181/361 (50.1%) | 331/361 (91.7%) |
| Avelumab Weekly | 237/322 (73.6%) | 143/318 (45%) | 298/318 (93.7%) |
| Chemotherapy | 405/526 (77%) | 195/500 (39%) | 474/500 (94.8%) |
| Event | Avelumab Biweekly | Avelumab Weekly | Chemotherapy |
|---|---|---|---|
| Disease progressionGeneral disorders | 33/361 | 18/318 | 22/500 |
| PneumoniaInfections and infestations | 28/361 | 13/318 | 28/500 |
| AnaemiaBlood and lymphatic system disorders | 4/361 | 2/318 | 19/500 |
| Pleural effusionRespiratory, thoracic and mediastinal disorders | 11/361 | 3/318 | 7/500 |
| Infusion related reactionInjury, poisoning and procedural complications | 11/361 | 7/318 | 0/500 |
| Febrile neutropeniaBlood and lymphatic system disorders | 0/361 | 0/318 | 13/500 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 9/361 | 5/318 | 8/500 |
| PneumonitisRespiratory, thoracic and mediastinal disorders | 8/361 | 5/318 | 0/500 |
| Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders | 5/361 | 6/318 | 3/500 |
| Decreased appetiteMetabolism and nutrition disorders | 2/361 | 6/318 | 2/500 |
| Event | Avelumab Biweekly | Avelumab Weekly | Chemotherapy |
|---|---|---|---|
| AnaemiaBlood and lymphatic system disorders | 37/361 | 57/318 | 232/500 |
| NauseaGastrointestinal disorders | 41/361 | 33/318 | 164/500 |
| NeutropeniaBlood and lymphatic system disorders | 6/361 | 3/318 | 113/500 |
| FatigueGeneral disorders | 58/361 | 56/318 | 99/500 |
| Decreased appetiteMetabolism and nutrition disorders | 65/361 | 61/318 | 90/500 |
| ConstipationGastrointestinal disorders | 59/361 | 21/318 | 87/500 |
| AstheniaGeneral disorders | 58/361 | 54/318 | 74/500 |
| PyrexiaGeneral disorders | 51/361 | 50/318 | 32/500 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 50/361 | 50/318 | 49/500 |
| VomitingGastrointestinal disorders | 19/361 | 24/318 | 73/500 |
| Age, Categorical(Participants) | Avelumab Biweekly | Avelumab Weekly | Chemotherapy | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 190 | 168 | 289 | 647 |
| >=65 years | 176 | 154 | 237 | 567 |
| Sex: Female, Male(Participants) | Avelumab Biweekly | Avelumab Weekly | Chemotherapy | Total |
|---|---|---|---|---|
| Female | 84 | 69 | 145 | 298 |
| Male | 282 | 253 | 381 | 916 |
| Ethnicity (NIH/OMB)(Participants) | Avelumab Biweekly | Avelumab Weekly | Chemotherapy | Total |
|---|---|---|---|---|
| Hispanic or Latino | 14 | 20 | 38 | 72 |
| Not Hispanic or Latino | 338 | 296 | 466 | 1100 |
| Unknown or Not Reported | 14 | 6 | 22 | 42 |
| Race (NIH/OMB)(Participants) | Avelumab Biweekly | Avelumab Weekly | Chemotherapy | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 85 | 53 | 104 | 242 |
| Native Hawaiian or Other Pacific Islander | 1 | 0 | 0 | 1 |
| Black or African American | 1 | 2 | 4 | 7 |
| White | 254 | 250 | 375 | 879 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 25 | 17 | 43 | 85 |
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Carcinoma, Non-Small-Cell Lung→
EMD Serono Research & Development Institute, Inc.