Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
Avelumab, MSB0010718C, Non-Small Cell Lung Cancer, Anti-PD-L1
Brief summary
The main purpose of this study was to demonstrate superiority with regard to overall survival of avelumab versus docetaxel in participants with programmed death ligand 1 (PD-L1) positive, non-small cell lung cancer (NSCLC) after failure of a platinum-based doublet.
Interventions
DRUGAvelumab
Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
DRUGDocetaxel
Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled.
Sponsors
Merck KGaA, Darmstadt, Germany
EMD Serono Research & Development Institute, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed written informed consent before any trial related procedure * Male or female participants aged greater than or equal to (\>=) 18 years * Availability of a formalin-fixed, paraffin-embedded block containing tumor tissue or 7 unstained tumor slides suitable for PD-L1 expression assessment * Tumor determined to be evaluable for PD-L1 expression per the evaluation of a central laboratory * Participants with histologically confirmed Stage IIIb/IV or recurrent NSCLC who have experienced disease progression * Participants must have progressed after an acceptable therapy defined as follows: 1. Participants must have progressed during or after a minimum of 2 cycles of 1 course of a platinum based combination therapy administered for the treatment of a metastatic disease. A history of continuation (use of a non platinum agent from initial combination) or switch (use of a different agent) maintenance therapy is permitted provided there was no progression after the initial combination. A switch of agents during treatment for the management of toxicities is also permitted provided there was no progression after the initial combination OR 2. Participants must have progressed within 6 months of completion of a platinum-based adjuvant, neoadjuvant, or definitive chemotherapy, or concomitant chemoradiation regimen for locally advanced disease * Participants with non-squamous cell NSCLC of unknown epidermal growth factor receptor (EGFR) mutation status will require testing (local laboratory, or central laboratory if local testing is not available). Participants with a tumor that harbors an activating EGFR mutation will not be eligible * Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at trial entry * Estimated life expectancy of more than 12 weeks * Adequate hematological function defined by White Blood Cell (WBC) count \>= 2.5 × 10\^9/L with absolute neutrophil count (ANC) \>= 1.5 × 10\^9/L, lymphocyte count \>=0.5 × 10\^9/L, platelet count \>= 100 × 10\^9/L, and hemoglobin \>= 9 gram per deciliter (g/dL) (may have been transfused) * Adequate hepatic function defined by a total bilirubin level less than or equal to (\<=) 1.5 × the upper limit of normal (ULN) range and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels \<= 2.5 × ULN for all participants * Adequate renal function defined by an estimated creatinine clearance \> 30 milliliter per minute (mL/min) according to the Cockcroft-Gault formula (or local institutional standard method). Other protocol defined inclusion criteria could apply
Exclusion criteria
* In the United States only, participants with a squamous cell histology will be excluded * Systemic anticancer therapy administered after disease progression during or following a platinum based combination * Participants with non-squamous cell NSCLC whose disease harbors EGFR mutation(s) and/or anaplastic lymphoma kinase (ALK) rearrangement will not be eligible for this trial. Participants of unknown ALK and/or EGFR mutation status will require testing at screening (local laboratory, or central laboratory if local testing is not available) * Prior therapy with any antibody/drug targeting T cell coregulatory proteins (immune checkpoints) such as PD-1, PD L1, or cytotoxic T lymphocyte antigen-4 (CTLA-4). * Concurrent anticancer treatment * Major surgery for any reason, except diagnostic biopsy, within 4 weeks of randomization and/or if the participant has not fully recovered from the surgery within 4 weeks of randomization * Participants receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of the trial treatment. * All participants with brain metastases, except those meeting the following criteria: 1. Brain metastases have been treated locally, and 2. No ongoing neurological symptoms that are related to the brain localization of the disease * Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent: 1. Participants with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible 2. Participants requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses less than or equal to (\<=)10 milligram (mg) or equivalent prednisone per day 3. Administration of steroids through a route known to result in a minimal systemic exposure are acceptable * Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon is acceptable as long as it is anticipated that the administration of steroids will be completed in 14 days, or that the daily dose after 14 days will be \<=10 mg per day of equivalent prednisone Other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) Time in Programmed Death Ligand 1 (PD-L1) + Full Analysis Set Population (FAS) | Time from date of randomization up to 1420 days | The OS time was defined as the time from randomization to the date of 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) Time in PD-L1+ Full Analysis Set Population | Time from date of randomization up to 907 days | PFS was 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. PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as adjudicated by independent endpoint review committee (IERC). PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. PFS was measured using Kaplan-Meier (KM) estimates. |
| Progression-Free Survival (PFS) Time in Full Analysis Set Population | Time from date of randomization up to 907 days | PFS was 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. PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as adjudicated by independent endpoint review committee (IERC). PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. PFS was measured using Kaplan-Meier (KM) estimates. |
| Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population | Time from date of randomization up to 907 days | Confirmed BOR was determined according to RECIST v1.1 and as adjudicated by an IERC. Confirmed BOR was defined as the best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). 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. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Number of participants with best overall response in each category (CR, PR, SD, PD) was reported. |
| Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population | Time from date of randomization up to 907 days | Confirmed BOR was determined according to RECIST v1.1 and as adjudicated by an IERC. Confirmed BOR was defined as the best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). 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. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Number of participants with best overall response in each category (CR, PR, SD, PD) was reported. |
| Percentage of Participants With Objective Response as Assessed by Independent Endpoint Review Committee (IERC) in Full Analysis Set Population | Time from date of randomization up to 907 days | Percentage of participants with objective response (CR plus PR) according to RECIST v1.1 was reported. 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 With Objective Response as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population | Time from date of randomization up to 907 days | Percentage of participants with objective response (CR plus PR) according to RECIST v1.1 was reported. 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. |
| Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Composite Index Score at End of Treatment (EOT) | Baseline, End of treatment visit (up to Week 124) | The EQ-5D-5L health outcome questionnaire was a measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L defined health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 items were combined to generate health profiles. These profiles were converted to a continuous single index score. The lowest possible score was -0.59 (unable to walk, unable to self-care, unable to do usual activities, extreme pain or discomfort, extreme anxiety or depression) and the highest was 1.00 (no problems in all 5 dimensions). |
| Overall Survival (OS) Time in Full Analysis Set Population | Time from date of randomization up to 1420 days | The OS time was defined as the time from randomization to the date of 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. |
| 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) | Baseline, End of treatment visit (up to Week 124) | 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. |
| 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) | Baseline, End of treatment visit (up to Week 124) | 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, 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). |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Drug Related Treatment Emergent Adverse Events and Treatment Emergent Adverse Events Leading to Death | Time from date of randomization up to 1420 days | An Adverse event (AE) was defined as any unfavorable and unintended sign (including clinically significant abnormal laboratory, vital signs and 12-lead Electrocardiogram findings), symptom, or disease temporally associated with the use of study drug or worsening of pre-existing medical condition, whether or not related to study drug. 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. Treatment-emergent events were the events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state up to 30 days after last administration. TEAEs included both Serious TEAEs and non-serious TEAEs. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity | Time from date of randomization up to 1420 days | Treatment Emergent Adverse Events were graded as per National Cancer Institute Common Terminology Criteria for Adverse Experience version 4.03 (NCI-CTCAE v 4.03). Grade 3 refers to severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care and Activity of daily living (ADL), Grade 4 refers to Life-threatening consequences; where urgent intervention indicated, Grade 5 refers to the death related to adverse event. |
| Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Time from date of randomization up to 1420 days | 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. The participants with missing worst post baseline score were also reported. ECOG performance status was reported in terms of number of participants with Baseline value vs. worst post-baseline value (i.e. highest score) combination. |
| Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) for Avelumab | Time from date of randomization up to 1420 days | 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. |
| Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Visual Analogue Scale (VAS) at End of Treatment (EOT) | Baseline, End of treatment visit (up to Week 124) | EQ-5D-5L was comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension had 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses were used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 was the worst health you can imagine and 100 was the best health you can imagine. |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Chile, Colombia, Croatia, Czechia, Denmark, France, Hungary, Israel, Italy, Japan, Mexico, Peru, Poland, Romania, Russia, Slovakia, South Africa, South Korea, Spain, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
First participant signed informed consent: 24 Mar 2015, Clinical data cut-off: 04 March 2019.
Participants by arm
| Arm | Count |
|---|---|
| Avelumab Participants received 10 milligrams per kilogram (mg/kg) of avelumab as a 1-hour intravenous infusion once every 2 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled. | 396 |
| Docetaxel Participants received 75 mg per square meter (m\^2) (per label) of docetaxel by intravenous infusion once every 3 weeks until confirmed disease progression, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the study or Investigational Medicinal Product (IMP) as defined in the study protocol was fulfilled. | 396 |
| Total | 792 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Participants randomized but not treated | 3 | 31 |
Baseline characteristics
| Characteristic | Docetaxel | Total | Avelumab |
|---|---|---|---|
| Age, Continuous | 62.5 years STANDARD_DEVIATION 9.65 | 62.7 years STANDARD_DEVIATION 9.81 | 62.8 years STANDARD_DEVIATION 9.99 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 42 Participants | 101 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 307 Participants | 604 Participants | 297 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 47 Participants | 87 Participants | 40 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 114 Participants | 216 Participants | 102 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 6 Participants | 5 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not collected at the site | 14 Participants | 28 Participants | 14 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 5 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 262 Participants | 535 Participants | 273 Participants |
| Sex: Female, Male Female | 123 Participants | 250 Participants | 127 Participants |
| Sex: Female, Male Male | 273 Participants | 542 Participants | 269 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 316 / 393 | 297 / 365 |
| other Total, other adverse events | 320 / 393 | 307 / 365 |
| serious Total, serious adverse events | 167 / 393 | 145 / 365 |
Outcome results
Primary
Overall Survival (OS) Time in Programmed Death Ligand 1 (PD-L1) + Full Analysis Set Population (FAS)
The OS time was defined as the time from randomization to the date of 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 1420 days
Population: PD-L1+ FAS included all PD-L1+ tumor participants who were randomly assigned to trial treatment. The PD-L1+ participants were with greater than or equal to (\>=) 1 percentage (%) of tumor cells with \>=1+ positive membrane staining intensity for PD-L1 protein.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab | Overall Survival (OS) Time in Programmed Death Ligand 1 (PD-L1) + Full Analysis Set Population (FAS) | 11.4 months |
| Docetaxel | Overall Survival (OS) Time in Programmed Death Ligand 1 (PD-L1) + Full Analysis Set Population (FAS) | 10.6 months |
p-value: =0.072195% CI: [0.71, 1.05]Log Rank
Secondary
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)
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 visit (up to Week 124)
Population: Health-related quality of life (HRQoL) analysis set was a subset of the FAS and includes all FAS participants who had 1 baseline HRQoL assessment and at least 1 post-baseline HRQoL questionnaire completed. Here, Overall Number of Participants Analyzed signified the participants analyzed in this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Avelumab | 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) | -9.79 units on a scale | Standard Deviation 24.506 |
| Docetaxel | 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) | -9.44 units on a scale | Standard Deviation 18.933 |
Secondary
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)
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, 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 visit (up to Week 124)
Population: Health-related quality of life (HRQoL) analysis set was a subset of the FAS and includes all FAS participants who had 1 baseline HRQoL assessment and at least 1 post-baseline HRQoL questionnaire completed. Here, Number Analyzed signified those participants who were evaluable for the specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Avelumab | 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) | Pain in Other Parts | 8.77 units on a scale | Standard Deviation 34.41 |
| Avelumab | 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) | Coughing | -0.58 units on a scale | Standard Deviation 30.263 |
| Avelumab | 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) | Hemoptysis | 0.19 units on a scale | Standard Deviation 14.191 |
| Avelumab | 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) | Sore Mouth | 0.78 units on a scale | Standard Deviation 17.643 |
| Avelumab | 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) | Dysphagia | 5.62 units on a scale | Standard Deviation 18.401 |
| Avelumab | 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) | Peripheral Neuropathy | 0.19 units on a scale | Standard Deviation 20.55 |
| Avelumab | 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) | Alopecia | -3.10 units on a scale | Standard Deviation 20.789 |
| Avelumab | 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) | Pain in Chest | 4.84 units on a scale | Standard Deviation 28.993 |
| Avelumab | 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) | Pain in Arm or Shoulder | 5.62 units on a scale | Standard Deviation 28.852 |
| Avelumab | 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) | Dyspnea | 9.95 units on a scale | Standard Deviation 22.094 |
| Docetaxel | 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) | Pain in Chest | 0.34 units on a scale | Standard Deviation 26.935 |
| Docetaxel | 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) | Dyspnea | 8.52 units on a scale | Standard Deviation 21.285 |
| Docetaxel | 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) | Peripheral Neuropathy | 9.81 units on a scale | Standard Deviation 30.015 |
| Docetaxel | 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) | Coughing | -2.03 units on a scale | Standard Deviation 32.582 |
| Docetaxel | 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) | Pain in Other Parts | 6.60 units on a scale | Standard Deviation 30.978 |
| Docetaxel | 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) | Hemoptysis | -0.34 units on a scale | Standard Deviation 16.832 |
| Docetaxel | 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) | Alopecia | 30.80 units on a scale | Standard Deviation 42.582 |
| Docetaxel | 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) | Sore Mouth | 3.72 units on a scale | Standard Deviation 24.92 |
| Docetaxel | 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) | Pain in Arm or Shoulder | 0.85 units on a scale | Standard Deviation 29.439 |
| Docetaxel | 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) | Dysphagia | 4.23 units on a scale | Standard Deviation 21.538 |
Secondary
Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Composite Index Score at End of Treatment (EOT)
The EQ-5D-5L health outcome questionnaire was a measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L defined health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 items were combined to generate health profiles. These profiles were converted to a continuous single index score. The lowest possible score was -0.59 (unable to walk, unable to self-care, unable to do usual activities, extreme pain or discomfort, extreme anxiety or depression) and the highest was 1.00 (no problems in all 5 dimensions).
Time frame: Baseline, End of treatment visit (up to Week 124)
Population: Health-related quality of life (HRQoL) analysis set was a subset of the FAS and includes all FAS participants who had 1 baseline HRQoL assessment and at least 1 post-baseline HRQoL questionnaire completed. Here, Overall Number of Participants Analyzed signified the participants analyzed in this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Avelumab | Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Composite Index Score at End of Treatment (EOT) | -0.1245 units on a scale | Standard Deviation 0.28021 |
| Docetaxel | Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Composite Index Score at End of Treatment (EOT) | -0.0988 units on a scale | Standard Deviation 0.26615 |
Secondary
Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Visual Analogue Scale (VAS) at End of Treatment (EOT)
EQ-5D-5L was comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension had 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses were used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 was the worst health you can imagine and 100 was the best health you can imagine.
Time frame: Baseline, End of treatment visit (up to Week 124)
Population: Health-related quality of life (HRQoL) analysis set was a subset of the FAS and includes all FAS participants who had 1 baseline HRQoL assessment and at least 1 post-baseline HRQoL questionnaire completed. Here, Overall Number of Participants Analyzed signified the participants analyzed in this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Avelumab | Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Visual Analogue Scale (VAS) at End of Treatment (EOT) | -8.1 millimeter | Standard Deviation 22.06 |
| Docetaxel | Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Visual Analogue Scale (VAS) at End of Treatment (EOT) | -7.0 millimeter | Standard Deviation 21.12 |
Secondary
Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population
Confirmed BOR was determined according to RECIST v1.1 and as adjudicated by an IERC. Confirmed BOR was defined as the best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). 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. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Number of participants with best overall response in each category (CR, PR, SD, PD) was reported.
Time frame: Time from date of randomization up to 907 days
Population: Full analysis set (FAS) included all participants who were randomized to study.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Avelumab | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population | Progressive Disease | 150 Participants |
| Avelumab | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population | Stable Disease | 129 Participants |
| Avelumab | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population | Not Evaluable | 53 Participants |
| Avelumab | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population | Partial Response | 54 Participants |
| Avelumab | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population | Complete Response | 5 Participants |
| Avelumab | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population | Non-complete Response/ Non-progressive Disease | 5 Participants |
| Docetaxel | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population | Non-complete Response/ Non-progressive Disease | 13 Participants |
| Docetaxel | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population | Partial Response | 42 Participants |
| Docetaxel | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population | Stable Disease | 158 Participants |
| Docetaxel | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population | Progressive Disease | 82 Participants |
| Docetaxel | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population | Not Evaluable | 99 Participants |
| Docetaxel | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by an Independent Endpoint Review Committee (IERC) in Full Analysis Set Population | Complete Response | 2 Participants |
Secondary
Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population
Confirmed BOR was determined according to RECIST v1.1 and as adjudicated by an IERC. Confirmed BOR was defined as the best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). 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. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Number of participants with best overall response in each category (CR, PR, SD, PD) was reported.
Time frame: Time from date of randomization up to 907 days
Population: PD-L1+ FAS included all PD-L1+ tumor participants who were randomly assigned to trial treatment. The PD-L1+ participants were with \>= 1 percentage of tumor cells with \>=1+ positive membrane staining intensity for PD-L1 protein.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Avelumab | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population | Complete Response | 4 Participants |
| Avelumab | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population | Partial Response | 46 Participants |
| Avelumab | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population | Stable Disease | 86 Participants |
| Avelumab | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population | Non-complete Response/ Non-progressive Disease | 4 Participants |
| Avelumab | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population | Progressive Disease | 93 Participants |
| Avelumab | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population | Not Evaluable | 31 Participants |
| Docetaxel | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population | Progressive Disease | 57 Participants |
| Docetaxel | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population | Complete Response | 1 Participants |
| Docetaxel | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population | Non-complete Response/ Non-progressive Disease | 12 Participants |
| Docetaxel | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population | Partial Response | 30 Participants |
| Docetaxel | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population | Not Evaluable | 61 Participants |
| Docetaxel | Number of Participants With Confirmed Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population | Stable Disease | 104 Participants |
Secondary
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score 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. The participants with missing worst post baseline score were also reported. ECOG performance status was reported in terms of number of participants with Baseline value vs. worst post-baseline value (i.e. highest score) combination.
Time frame: Time from date of randomization up to 1420 days
Population: Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Avelumab | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 1, worst post-baseline Missing | 12 Participants |
| Avelumab | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 0, worst post-baseline score 1 | 67 Participants |
| Avelumab | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 0, worst post-baseline score 2 | 19 Participants |
| Avelumab | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 0, worst post-baseline score 3 | 5 Participants |
| Avelumab | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 0, worst post-baseline score 4 | 0 Participants |
| Avelumab | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 0, worst post-baseline score 5 | 1 Participants |
| Avelumab | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 0, worst post-baseline Missing | 0 Participants |
| Avelumab | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 1, worst post-baseline score 0 | 6 Participants |
| Avelumab | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 1, worst post-baseline score 3 | 23 Participants |
| Avelumab | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 1, worst post-baseline score 5 | 1 Participants |
| Avelumab | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 1, worst post-baseline score 1 | 157 Participants |
| Avelumab | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 1, worst post-baseline score 2 | 47 Participants |
| Avelumab | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 1, worst post-baseline score 4 | 3 Participants |
| Avelumab | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 0, worst post-baseline score 0 | 52 Participants |
| Docetaxel | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 1, worst post-baseline score 1 | 172 Participants |
| Docetaxel | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 0, worst post-baseline score 0 | 55 Participants |
| Docetaxel | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 1, worst post-baseline score 4 | 2 Participants |
| Docetaxel | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 0, worst post-baseline score 1 | 41 Participants |
| Docetaxel | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 1, worst post-baseline score 3 | 8 Participants |
| Docetaxel | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 0, worst post-baseline score 2 | 12 Participants |
| Docetaxel | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 1, worst post-baseline score 2 | 41 Participants |
| Docetaxel | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 0, worst post-baseline score 3 | 2 Participants |
| Docetaxel | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 1, worst post-baseline Missing | 23 Participants |
| Docetaxel | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 0, worst post-baseline score 4 | 1 Participants |
| Docetaxel | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 1, worst post-baseline score 0 | 1 Participants |
| Docetaxel | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 0, worst post-baseline score 5 | 0 Participants |
| Docetaxel | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 1, worst post-baseline score 5 | 1 Participants |
| Docetaxel | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score | Baseline score 0, worst post-baseline Missing | 6 Participants |
Secondary
Number of Participants With 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 1420 days
Population: Full analysis set (FAS) included all participants who were randomized to study. Here, Overall Number of Participants Analyzed signified participants with at least on valid ADA result at any time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Avelumab | Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) for Avelumab | ADAs to Avelumab | 58 Participants |
| Avelumab | Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) for Avelumab | NAbs to Avelumab | 14 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity
Treatment Emergent Adverse Events were graded as per National Cancer Institute Common Terminology Criteria for Adverse Experience version 4.03 (NCI-CTCAE v 4.03). Grade 3 refers to severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care and Activity of daily living (ADL), Grade 4 refers to Life-threatening consequences; where urgent intervention indicated, Grade 5 refers to the death related to adverse event.
Time frame: Time from date of randomization up to 1420 days
Population: Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Avelumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity | Grade 3 or Higher | 209 Participants |
| Avelumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity | Grade 4 or Higher | 87 Participants |
| Avelumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity | Grade 5 | 63 Participants |
| Docetaxel | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity | Grade 3 or Higher | 247 Participants |
| Docetaxel | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity | Grade 4 or Higher | 122 Participants |
| Docetaxel | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity | Grade 5 | 51 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Drug Related Treatment Emergent Adverse Events and Treatment Emergent Adverse Events Leading to Death
An Adverse event (AE) was defined as any unfavorable and unintended sign (including clinically significant abnormal laboratory, vital signs and 12-lead Electrocardiogram findings), symptom, or disease temporally associated with the use of study drug or worsening of pre-existing medical condition, whether or not related to study drug. 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. Treatment-emergent events were the events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state up to 30 days after last administration. TEAEs included both Serious TEAEs and non-serious TEAEs.
Time frame: Time from date of randomization up to 1420 days
Population: Safety analysis set included all participants who were administered at least 1 dose of the Investigational Medicinal Product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Avelumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Drug Related Treatment Emergent Adverse Events and Treatment Emergent Adverse Events Leading to Death | TESAEs | 167 Participants |
| Avelumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Drug Related Treatment Emergent Adverse Events and Treatment Emergent Adverse Events Leading to Death | TEAEs Leading to Death | 64 Participants |
| Avelumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Drug Related Treatment Emergent Adverse Events and Treatment Emergent Adverse Events Leading to Death | Drug Related TEAEs | 252 Participants |
| Avelumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Drug Related Treatment Emergent Adverse Events and Treatment Emergent Adverse Events Leading to Death | TEAEs | 375 Participants |
| Docetaxel | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Drug Related Treatment Emergent Adverse Events and Treatment Emergent Adverse Events Leading to Death | TEAEs | 346 Participants |
| Docetaxel | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Drug Related Treatment Emergent Adverse Events and Treatment Emergent Adverse Events Leading to Death | TESAEs | 145 Participants |
| Docetaxel | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Drug Related Treatment Emergent Adverse Events and Treatment Emergent Adverse Events Leading to Death | Drug Related TEAEs | 313 Participants |
| Docetaxel | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Drug Related Treatment Emergent Adverse Events and Treatment Emergent Adverse Events Leading to Death | TEAEs Leading to Death | 51 Participants |
Secondary
Overall Survival (OS) Time in Full Analysis Set Population
The OS time was defined as the time from randomization to the date of 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 1420 days
Population: Full analysis set (FAS) included all participants who were randomized to study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab | Overall Survival (OS) Time in Full Analysis Set Population | 10.6 months |
| Docetaxel | Overall Survival (OS) Time in Full Analysis Set Population | 9.9 months |
95% CI: [0.77, 1.05]
Secondary
Percentage of Participants With Objective Response as Assessed by Independent Endpoint Review Committee (IERC) in Full Analysis Set Population
Percentage of participants with objective response (CR plus PR) according to RECIST v1.1 was reported. 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 907 days
Population: Full analysis set (FAS) included all participants who were randomized to study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avelumab | Percentage of Participants With Objective Response as Assessed by Independent Endpoint Review Committee (IERC) in Full Analysis Set Population | 14.9 percentage of participants |
| Docetaxel | Percentage of Participants With Objective Response as Assessed by Independent Endpoint Review Committee (IERC) in Full Analysis Set Population | 11.1 percentage of participants |
95% CI: [0.92, 2.13]
Secondary
Percentage of Participants With Objective Response as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population
Percentage of participants with objective response (CR plus PR) according to RECIST v1.1 was reported. 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 907 days
Population: PD-L1+ FAS included all PD-L1+ tumor participants who were randomly assigned to trial treatment. The PD-L1+ participants were with \>= 1 percentage of tumor cells with \>=1+ positive membrane staining intensity for PD-L1 protein.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Avelumab | Percentage of Participants With Objective Response as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population | 18.9 percentage of participants |
| Docetaxel | Percentage of Participants With Objective Response as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population | 11.7 percentage of participants |
95% CI: [1.08, 2.86]
Secondary
Progression-Free Survival (PFS) Time in Full Analysis Set Population
PFS was 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. PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as adjudicated by independent endpoint review committee (IERC). PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. PFS was measured using Kaplan-Meier (KM) estimates.
Time frame: Time from date of randomization up to 907 days
Population: Full analysis set (FAS) included all participants who were randomized to study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab | Progression-Free Survival (PFS) Time in Full Analysis Set Population | 2.8 months |
| Docetaxel | Progression-Free Survival (PFS) Time in Full Analysis Set Population | 4.2 months |
95% CI: [0.98, 1.41]
Secondary
Progression-Free Survival (PFS) Time in PD-L1+ Full Analysis Set Population
PFS was 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. PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as adjudicated by independent endpoint review committee (IERC). PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. PFS was measured using Kaplan-Meier (KM) estimates.
Time frame: Time from date of randomization up to 907 days
Population: PD-L1+ FAS included all PD-L1+ tumor participants who were randomly assigned to trial treatment. The PD-L1+ participants were with \>= 1 percentage of tumor cells with \>=1+ positive membrane staining intensity for PD-L1 protein.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Avelumab | Progression-Free Survival (PFS) Time in PD-L1+ Full Analysis Set Population | 3.4 months |
| Docetaxel | Progression-Free Survival (PFS) Time in PD-L1+ Full Analysis Set Population | 4.1 months |
95% CI: [0.8, 1.27]