Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
Lung neoplasms, Lung cancer, Non-small Cell Lung Cancer, pemetrexed, squamous, nonsquamous
Brief summary
The purpose of this study is to determine if participants with Stage IV NSCLC have a better outcome when treated with IMC-1121B in combination with pemetrexed + carboplatin/cisplatin or gemcitabine + carboplatin/cisplatin than when treated with pemetrexed + carboplatin/cisplatin or gemcitabine + carboplatin/cisplatin alone.
Interventions
BIOLOGICALIMC-1121B (ramucirumab)
10 milligrams/kilogram (mg/kg) once every 3 weeks beginning Day 1, Cycle 1
DRUGPemetrexed
500 milligrams/square meter (mg/m²) on Day 1 of every 21-day cycle
Day 1 of every 21-day cycle
DRUGCisplatin
75 mg/m² intravenous (IV) on Day 1 of each 21-day cycle
DRUGGemcitabine
1000 mg/m² on Days 1 and 8 of every 21-day cycle
Day 1 of every 21-day cycle
Sponsors
Eli Lilly and Company
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
* Confirmed NSCLC * Stage IV disease at the time of study entry * Measurable disease at the time of study entry * Resolution to Grade ≤ 1 Adverse Events, of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy (except alopecia) * Adequate hematologic function, hepatic function, renal function and coagulation function * If sexually active, must be post-menopausal, surgically sterile, or using effective contraception; and agrees to use adequate contraception during the study period and for up to 6 months after the last dose of study medication * Female participants of childbearing potential must have a negative serum pregnancy test
Exclusion criteria
* Has cirrhosis at a level of Child-Pugh B (or worse), or cirrhosis and a history of hepatic encephalopathy, or ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis * Tumor wholly or partially contains small cell lung cancer * Untreated central nervous system (CNS) metastases, eligible if they are clinically stable with regard to neurologic function, off all steroids after cranial irradiation at least 2 weeks prior or after surgical resection performed at least 4 weeks prior to randomization * Concurrent active malignancy other than adequately treated basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix. A participant with previous history of malignancy other than NSCLC is eligible, provided that he/she has been free of disease for ≥ 3 years * Received prior therapy with monoclonal antibodies, signal transduction inhibitors, or any therapies targeting the vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor (VEGFR) * Receiving concurrent treatment with other anticancer therapy * Has received previous chemotherapy for Stage IV NSCLC (participants who have received adjuvant chemotherapy are eligible if the last administration of the prior adjuvant regimen occurred at least 6 months prior to randomization) * Has radiologically documented evidence of major blood vessel invasion or encasement by cancer * Has undergone chest irradiation within 12 weeks prior to randomization (except palliative irradiation of bone lesions) * Ongoing or active infection * History of significant neurological or psychiatric disorders * Experienced clinically relevant coronary artery disease, myocardial infarction within 6 months prior to randomization, uncontrolled congestive heart failure, or symptomatic poorly controlled arrhythmia * Poorly-controlled hypertension * Experienced any serious Grade 3-4 gastrointestinal bleeding within 3 months prior to study entry * Receiving chronic daily treatment with aspirin (\> 325 mg/day) or other known inhibitors of platelet function * Serious nonhealing wound, ulcer, or bone fracture within 28 days prior to randomization * Major surgery within 28 days prior the first dose of study medication, or subcutaneous venous access device placement within 7 days prior to randomization * Elective or a planned major surgery * Pregnant or lactating * Any other serious uncontrolled medical disorders or psychological conditions * Allergy / history of hypersensitivity reaction to any of the treatment components * History of drug abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Randomization to PD or death (up to 24 months) | PFS was the time from randomization to the first objective progression as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v 1.1) or death from any cause, whichever occurred first. Progressive disease (PD) was defined as ≥20% increase in sum of diameter (SOD) of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 millimeters (mm); appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants alive and without disease progression were censored at the time of the last objective tumor assessment. Participants who did not progress and were lost to follow-up were censored at their last radiographic assessment. If no baseline or post baseline radiologic assessments were available, participants were censored at date of randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] | Day 1, Cycle 1 (3-week cycles) and every 6 weeks thereafter to PD (up to 24 months) | Best overall response of CR or PR was defined using RECIST v 1.1 criteria. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to \<10 mm, and normalization of tumor marker levels of non-target lesions. PR was defined as ≥30% decrease in SOD of target lesions taking as reference the baseline sum diameter. PD was defined as ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR/total number of participants)\*100. |
| Overall Survival (OS) | Randomization to the date of death from any cause (up to 31.3 months) | OS was defined as the time from the date of randomization to the date of death from any cause. If the participant was alive at the end of the follow-up period or was lost to follow-up, OS was censored on the last date the participant was known to be alive. |
| Duration of Response (DOR) | Time of first response (CR or PR) until PD or death (up to 24 months) | DOR was measured from the time criteria were met for the first objectively recorded CR or PR until the first date criteria for PD were met or death. Response was defined using RECIST v 1.1 criteria. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to \<10 mm, and normalization of tumor marker level of non-target lesions. PR was defined as ≥30% decrease SOD of target lesions taking as reference the baseline sum diameter. PD was defined as ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants who did not relapse were censored at the day of their last objective tumor assessment. |
| Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Who Died | Day 1, Cycle 1 (3-week cycles) Up to 3 Years | Data presented are the number of participants with at least 1 treatment-emergent adverse event (TEAE) and treatment-emergent serious adverse event (SAE), as well as, the number of participants who died during the study. TEAEs were defined as serious and other non-serious AEs that occurred or worsened after study treatment (regardless of causality). A summary of SAEs and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With CR, PR, or Stable Disease (SD) [Disease Control Rate (DCR)] | Day 1, Cycle 1 (3-week cycles) and every 6 weeks thereafter to PD (up to 24 months) | DCR: percentage of participants with CR, PR, or SD using RECIST v 1.1 criteria. CR: disappearance of all lesions, pathological lymph node reduction in short axis to \<10 mm, and normalization of tumor marker levels of non-target lesions. PR: ≥30% decrease in SOD of target lesions taking as reference baseline sum diameter. PD: ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference smallest sum of longest diameters recorded since treatment started and an absolute increase in sum diameter ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. SD: neither sufficient shrinkage to qualify for PR nor increase to qualify for PD. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR+SD/total number of participants)\*100. |
| Change in Tumor Size (CTS) | Baseline, 6 weeks | CTS was defined as the log ratio of tumor size at 6 weeks to tumor size at baseline. CTS at 6 weeks=Log (Sum of Target Lesion Measurements at 6 Weeks)-Log (Sum of Target Lesion Measurements at Baseline). |
Countries
Belgium, Canada, Germany, Poland, United Kingdom, United States
Participant flow
Pre-assignment details
Participants who died (any cause) or had disease progression were considered to be study completers.
Participants by arm
| Arm | Count |
|---|---|
| Pem + Carb or Cis (Non-Squamous) Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks. | 71 |
| Ram + Pem + Carb or Cis (Non-Squamous) Ram: 10 mg/kg Day 1 of every 21-day cycle. Pem: 500 mg/m² on Day 1 of every 21-day cycle. Carb (AUC 6): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks. | 69 |
| Gem + Carb or Cis (Squamous) Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks. | 69 |
| Ram + Gem + Carb or Cis (Squamous) Ram: 10 mg/kg on Day 1 of each every 21-day cycle. Gem: 1000 mg/m² on Days 1 and 8 of every 21-day cycle. Carb (AUC 5): Day 1 of every 21-day cycle. Cis: 75 mg/m² IV on Day 1 of every 21-day cycle. Participants were treated for up to 89 weeks. | 71 |
| Total | 280 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Not meet inclusion/exclusion criteria | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 11 | 5 | 6 | 4 |
Baseline characteristics
| Characteristic | Pem + Carb or Cis (Non-Squamous) | Ram + Pem + Carb or Cis (Non-Squamous) | Gem + Carb or Cis (Squamous) | Ram + Gem + Carb or Cis (Squamous) | Total |
|---|---|---|---|---|---|
| Age, Customized <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >=65 years | 34 Participants | 32 Participants | 40 Participants | 37 Participants | 143 Participants |
| Age, Customized Between 18 and 65 years | 37 Participants | 37 Participants | 27 Participants | 34 Participants | 135 Participants |
| Age, Customized Missing Data | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 1 Participants | 0 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 70 Participants | 65 Participants | 68 Participants | 71 Participants | 274 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 6 Participants |
| Race/Ethnicity, Customized Black | 2 Participants | 8 Participants | 1 Participants | 4 Participants | 15 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 65 Participants | 60 Participants | 65 Participants | 67 Participants | 257 Participants |
| Region of Enrollment Belgium | 0 Participants | 0 Participants | 5 Participants | 4 Participants | 9 Participants |
| Region of Enrollment Canada | 0 Participants | 0 Participants | 4 Participants | 1 Participants | 5 Participants |
| Region of Enrollment Germany | 0 Participants | 0 Participants | 14 Participants | 8 Participants | 22 Participants |
| Region of Enrollment Poland | 0 Participants | 0 Participants | 4 Participants | 12 Participants | 16 Participants |
| Region of Enrollment United Kingdom | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 5 Participants |
| Region of Enrollment United States | 71 Participants | 69 Participants | 42 Participants | 41 Participants | 223 Participants |
| Sex: Female, Male Female | 26 Participants | 33 Participants | 26 Participants | 16 Participants | 101 Participants |
| Sex: Female, Male Male | 45 Participants | 36 Participants | 43 Participants | 55 Participants | 179 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 51 / 69 | 55 / 67 | 55 / 63 | 56 / 71 |
| other Total, other adverse events | 67 / 69 | 66 / 67 | 62 / 63 | 71 / 71 |
| serious Total, serious adverse events | 38 / 69 | 44 / 67 | 29 / 63 | 39 / 71 |
Outcome results
Primary
Progression-Free Survival (PFS)
PFS was the time from randomization to the first objective progression as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v 1.1) or death from any cause, whichever occurred first. Progressive disease (PD) was defined as ≥20% increase in sum of diameter (SOD) of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 millimeters (mm); appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants alive and without disease progression were censored at the time of the last objective tumor assessment. Participants who did not progress and were lost to follow-up were censored at their last radiographic assessment. If no baseline or post baseline radiologic assessments were available, participants were censored at date of randomization.
Time frame: Randomization to PD or death (up to 24 months)
Population: Intent-to-Treat (ITT) Population: All randomized participants. Participants censored: Pem+Carb/Cis=14, Ram+Pem+Carb/Cis=13, Gem+Carb/Cis=14, Ram+Gem+Carb/Cis=18.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pem + Carb or Cis (Non-Squamous) | Progression-Free Survival (PFS) | 5.6 months |
| Ram + Pem + Carb or Cis (Non-Squamous) | Progression-Free Survival (PFS) | 7.2 months |
| Gem + Carb or Cis (Squamous) | Progression-Free Survival (PFS) | 5.4 months |
| Ram + Gem + Carb or Cis (Squamous) | Progression-Free Survival (PFS) | 5.6 months |
p-value: 0.131890% CI: [0.55, 1.03]Log Rank
p-value: 0.521590% CI: [0.64, 1.22]Log Rank
Secondary
Duration of Response (DOR)
DOR was measured from the time criteria were met for the first objectively recorded CR or PR until the first date criteria for PD were met or death. Response was defined using RECIST v 1.1 criteria. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to \<10 mm, and normalization of tumor marker level of non-target lesions. PR was defined as ≥30% decrease SOD of target lesions taking as reference the baseline sum diameter. PD was defined as ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants who did not relapse were censored at the day of their last objective tumor assessment.
Time frame: Time of first response (CR or PR) until PD or death (up to 24 months)
Population: All randomized participants with a best overall response of CR or PR. Participants censored: Pem+Carb/Cis=44, Ram+Pem+Carb/Cis=35, Gem+Carb/Cis=50, Ram+Gem+Carb/Cis=37.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pem + Carb or Cis (Non-Squamous) | Duration of Response (DOR) | 4.5 months |
| Ram + Pem + Carb or Cis (Non-Squamous) | Duration of Response (DOR) | 5.5 months |
| Gem + Carb or Cis (Squamous) | Duration of Response (DOR) | 4.3 months |
| Ram + Gem + Carb or Cis (Squamous) | Duration of Response (DOR) | 4.3 months |
Secondary
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Who Died
Data presented are the number of participants with at least 1 treatment-emergent adverse event (TEAE) and treatment-emergent serious adverse event (SAE), as well as, the number of participants who died during the study. TEAEs were defined as serious and other non-serious AEs that occurred or worsened after study treatment (regardless of causality). A summary of SAEs and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
Time frame: Day 1, Cycle 1 (3-week cycles) Up to 3 Years
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pem + Carb or Cis (Non-Squamous) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Who Died | Deaths | 51 Participants |
| Pem + Carb or Cis (Non-Squamous) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Who Died | Treatment-Emergent Adverse Event | 68 Participants |
| Pem + Carb or Cis (Non-Squamous) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Who Died | Treatment-Emergent SAE | 38 Participants |
| Ram + Pem + Carb or Cis (Non-Squamous) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Who Died | Deaths | 55 Participants |
| Ram + Pem + Carb or Cis (Non-Squamous) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Who Died | Treatment-Emergent SAE | 44 Participants |
| Ram + Pem + Carb or Cis (Non-Squamous) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Who Died | Treatment-Emergent Adverse Event | 67 Participants |
| Gem + Carb or Cis (Squamous) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Who Died | Treatment-Emergent Adverse Event | 63 Participants |
| Gem + Carb or Cis (Squamous) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Who Died | Treatment-Emergent SAE | 29 Participants |
| Gem + Carb or Cis (Squamous) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Who Died | Deaths | 55 Participants |
| Ram + Gem + Carb or Cis (Squamous) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Who Died | Deaths | 56 Participants |
| Ram + Gem + Carb or Cis (Squamous) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Who Died | Treatment-Emergent Adverse Event | 71 Participants |
| Ram + Gem + Carb or Cis (Squamous) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Who Died | Treatment-Emergent SAE | 39 Participants |
Secondary
Overall Survival (OS)
OS was defined as the time from the date of randomization to the date of death from any cause. If the participant was alive at the end of the follow-up period or was lost to follow-up, OS was censored on the last date the participant was known to be alive.
Time frame: Randomization to the date of death from any cause (up to 31.3 months)
Population: ITT Population: All randomized participants. Participants censored: Pem+Carb/Cis=22, Ram+Pem+Carb/Cis=16, Gem+Carb/Cis=32, Ram+Gem+Carb/Cis=32. Censored participants were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pem + Carb or Cis (Non-Squamous) | Overall Survival (OS) | 10.4 months |
| Ram + Pem + Carb or Cis (Non-Squamous) | Overall Survival (OS) | 13.9 months |
| Gem + Carb or Cis (Squamous) | Overall Survival (OS) | 11.3 months |
| Ram + Gem + Carb or Cis (Squamous) | Overall Survival (OS) | 10.4 months |
p-value: 0.891690% CI: [0.74, 1.42]Log Rank
p-value: 0.684790% CI: [0.68, 1.27]Log Rank
Secondary
Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
Best overall response of CR or PR was defined using RECIST v 1.1 criteria. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to \<10 mm, and normalization of tumor marker levels of non-target lesions. PR was defined as ≥30% decrease in SOD of target lesions taking as reference the baseline sum diameter. PD was defined as ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR/total number of participants)\*100.
Time frame: Day 1, Cycle 1 (3-week cycles) and every 6 weeks thereafter to PD (up to 24 months)
Population: ITT Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pem + Carb or Cis (Non-Squamous) | Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] | 38.0 percentage of participants |
| Ram + Pem + Carb or Cis (Non-Squamous) | Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] | 49.3 percentage of participants |
| Gem + Carb or Cis (Squamous) | Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] | 24.6 percentage of participants |
| Ram + Gem + Carb or Cis (Squamous) | Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] | 46.5 percentage of participants |
p-value: 0.179790% CI: [0.9, 2.78]Chi-squared
p-value: 0.00790% CI: [1.45, 4.86]Chi-squared
Other Pre-specified
Change in Tumor Size (CTS)
CTS was defined as the log ratio of tumor size at 6 weeks to tumor size at baseline. CTS at 6 weeks=Log (Sum of Target Lesion Measurements at 6 Weeks)-Log (Sum of Target Lesion Measurements at Baseline).
Time frame: Baseline, 6 weeks
Population: All randomized participants with results at baseline and 6 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pem + Carb or Cis (Non-Squamous) | Change in Tumor Size (CTS) | -0.2 log ratio | Standard Deviation 0.23 |
| Ram + Pem + Carb or Cis (Non-Squamous) | Change in Tumor Size (CTS) | -0.2 log ratio | Standard Deviation 0.22 |
| Gem + Carb or Cis (Squamous) | Change in Tumor Size (CTS) | -0.3 log ratio | Standard Deviation 0.31 |
| Ram + Gem + Carb or Cis (Squamous) | Change in Tumor Size (CTS) | -0.4 log ratio | Standard Deviation 0.39 |
p-value: 0.1571t-test, 2 sided
p-value: 0.1597t-test, 2 sided
Other Pre-specified
Percentage of Participants With CR, PR, or Stable Disease (SD) [Disease Control Rate (DCR)]
DCR: percentage of participants with CR, PR, or SD using RECIST v 1.1 criteria. CR: disappearance of all lesions, pathological lymph node reduction in short axis to \<10 mm, and normalization of tumor marker levels of non-target lesions. PR: ≥30% decrease in SOD of target lesions taking as reference baseline sum diameter. PD: ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference smallest sum of longest diameters recorded since treatment started and an absolute increase in sum diameter ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. SD: neither sufficient shrinkage to qualify for PR nor increase to qualify for PD. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR+SD/total number of participants)\*100.
Time frame: Day 1, Cycle 1 (3-week cycles) and every 6 weeks thereafter to PD (up to 24 months)
Population: ITT Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pem + Carb or Cis (Non-Squamous) | Percentage of Participants With CR, PR, or Stable Disease (SD) [Disease Control Rate (DCR)] | 70.4 percentage of participants |
| Ram + Pem + Carb or Cis (Non-Squamous) | Percentage of Participants With CR, PR, or Stable Disease (SD) [Disease Control Rate (DCR)] | 85.5 percentage of participants |
| Gem + Carb or Cis (Squamous) | Percentage of Participants With CR, PR, or Stable Disease (SD) [Disease Control Rate (DCR)] | 66.7 percentage of participants |
| Ram + Gem + Carb or Cis (Squamous) | Percentage of Participants With CR, PR, or Stable Disease (SD) [Disease Control Rate (DCR)] | 73.2 percentage of participants |
p-value: 0.031690% CI: [1.22, 5.02]Chi-squared
p-value: 0.396290% CI: [0.74, 2.52]Chi-squared