Metastatic Non-Small Cell Lung Cancer
Conditions
Brief summary
The primary hypothesis is that pembrolizumab/vibostolimab (MK-7684A) in combination with chemotherapy is superior to pembrolizumab in combination with chemotherapy with respect to overall survival (OS) in participants with programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS) ≥1%.
Detailed description
Effective as of Amendment 5, Participants receiving coformulation of pembrolizumab/vibostolimab plus chemotherapy will be transitioned to standard of care (SOC, pembrolizumab plus chemotherapy). Participants with access to approved standard of care (SOC) should be considered for discontinuation from the study. Those benefiting from pembrolizumab plus chemotherapy, but unable to access it as SOC outside the study, may continue on study and receive treatment with pembrolizumab plus chemotherapy until discontinuation criteria are met.
Interventions
BIOLOGICALPembrolizumab/Vibostolimab
Co-formulation of pembrolizumab 200 mg/20 mL vial and vibostolimab 200 mg administered as IV infusion for up to 35 administrations
DRUGCarboplatin
Carboplatin 10 mg/ml administered as IV infusion Q3W for 4 administrations
DRUGCisplatin
Cisplatin 1 mg/ml administered as IV infusion Q3W for 4 administrations
DRUGPaclitaxel
Paclitaxel 6mg/ml administered as IV infusion Q3W for 4 administrations
DRUGNab-paclitaxel
Nab-paclitaxel 100 mg/vial administered as IV infusion Days 1, 8, and 15 of each 21-day cycle for 4 administrations
DRUGPemetrexed
Pemetrexed 500 mg/vial administered as IV infusion Q3W until progression, intolerable adverse event (AE), or participant or physician decision
BIOLOGICALPembrolizumab
Pembrolizumab 25 mg/mL administered as IV infusion Q3W for up to 35 administrations
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The main inclusion and
Exclusion criteria
include but are not limited to the following: Inclusion Criteria: * A histologically or cytologically confirmed diagnosis of Stage IV squamous or non-squamous NSCLC * Has not received prior systemic treatment for metastatic NSCLC * Has measurable disease based on RECIST 1.1, as determined by the local site assessment * Has a life expectancy of at least 3 months * Males: Use contraception unless confirmed to be azoospermic; Females: Women of childbearing potential use highly effective contraceptive method
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥1% | Up to approximately 29 months | OS is defined as the time from the date of randomization to death due to any cause. The OS is reported for all participants with PD-L1 positive tumors (PD-L1 TPS≥1%). The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in All Participants | Up to approximately 29 months | OS is defined as the time from the date of randomization to death due to any cause. The OS is reported for all randomized participants. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. |
| Progression-Free Survival (PFS) | Up to approximately 29 months | PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1). PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review (BICR) was planned to be presented. |
| Objective Response Rate (ORR) | Up to approximately 29 months | ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by blinded independent central review (BICR) was planned to be presented. |
| Duration of Response (DOR) | Up to approximately 29 months | For participants who demonstrate a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The DOR as assessed by BICR was planned to be presented. |
| Number of Participants Who Experienced One or More Adverse Events (AEs) | Up to approximately 46 months | The number of participants who experienced an adverse event (AE) will be presented. An AE is defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. |
| Change From Baseline in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) | Baseline and Up to approximately 29 months | Change from baseline in the score of EORTC QLQ-C30 Items 29 and 30 was planned to be presented. The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to Items 29 and 30 ("How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1=Very Poor to 7=Excellent). A higher score indicates a better overall outcome. |
| Change From Baseline in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30 | Baseline and Up to approximately 29 months | Change from baseline in the score of EORTC QLQ-C30 Items 1-5 was planned to be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a worse level of function. |
| Change From Baseline for Role Functioning (Items 6 and 7) Combined Score on the EORTC QLQ-C30 | Baseline and up to approximately 29 months | Change from baseline in the score of EORTC QLQ-C30 Items 6-7 was planned to be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 2 questions about their role functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a worse level of function. |
| Change From Baseline in Dyspnea Score (Item 8) on the EORTC QLQ-C30 | Baseline and Up to approximately 29 months | Change from baseline in the score of EORTC QLQ-C30 Item 8 was planned to be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant response to the question "Were you short of breath?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of dyspnea. |
| Change From Baseline in Cough Score (Item 31) on the European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-LC13) | Baseline and Up to approximately 29 months | Change from baseline in the score of EORTC QLQ-LC13 Item 31 was planned to be presented. The EORTC QLQ-LC13 is a lung cancer specific health-related quality-of life (QoL) questionnaire. Participant response to the question "Have you coughed?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates more frequent coughing. |
| Change From Baseline in Chest Pain Score (Item 40) on the EORTC QLQ- LC13 | Baseline and Up to approximately 29 months | Change from baseline in the score of EORTC QLQ-LC13 Item 40 was planned to be presented. The EORTC QLQ-LC13 is a lung cancer specific health-related quality-of life (QoL) questionnaire. Participant response to the question "Have you had pain in your chest?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of chest pain. |
| Time to Deterioration (TTD) in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the EORTC QLQ-C30 | Up to approximately 29 months | TTD in the score of EORTC QLQ-C30 Items 29 and 30 was planned to be presented. The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to Items 29 and 30 ("How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1=Very Poor to 7=Excellent). A higher score indicates a better overall outcome. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline. |
| TTD in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ- C30 | Up to approximately 29 months | TTD in the score of EORTC QLQ-C30 Items 1-5 was planned to be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a worse level of function. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline. |
| TTD in Role Functioning (Items 6 and 7) Combined Score on the EORTC QLQ-C30 | Up to approximately 29 months | TTD in the score of EORTC QLQ-C30 Items 6-7 was planned to be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 2 questions about their role functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a worse level of function. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline. |
| TTD in Dyspnea Score (Item 8) on the EORTC QLQ-C30 | Up to approximately 29 months | TTD in the score of EORTC QLQ-C30 Item 8 was planned to be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant response to the question "Were you short of breath?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of dyspnea. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline. |
| TTD in Cough Score (Item 31) on the EORTC QLQ-LC13 | Up to approximately 29 months | TTD in the score of EORTC QLQ-LC13 Item 31 was planned to be presented. The EORTC QLQ-LC13 is a lung cancer specific health-related quality-of life (QoL) questionnaire. Participant response to the question "Have you coughed?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates more frequent coughing. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline. |
| TTD in Chest Pain Score (Item 40) on the EORTC QLQ-LC13 | Up to approximately 29 months | TTD in the score of EORTC QLQ-LC13 Item 40 was planned to be presented. The EORTC QLQ-LC13 is a lung cancer specific health-related quality-of life (QoL) questionnaire. Participant response to the question "Have you had pain in your chest?" is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of chest pain. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline. |
| Number of Participants Who Discontinued Study Intervention Due to an AE | Up to approximately 46 months | The number of participants who discontinue study intervention due to an adverse event (AE) will be presented. An AE is defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. |
Countries
Argentina, Austria, Brazil, Chile, China, Colombia, France, Germany, Israel, Japan, Mexico, Poland, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MK-7684A + Chemotherapy Participants receive MK-7684A (co-formulation of 200mg pembrolizumab and 200 mg vibostolimab) via intravenous (IV) infusion on Day 1 of each cycle (cycle length = 3 weeks) for up to 35 cycles (up to \
2 years) PLUS paclitaxel IV (on Day 1 of each cycle) OR nab-paclitaxel IV (on Days 1, 8, and 15 of each cycle) and carboplatin IV (on Day 1 of each cycle) for 4 cycles for Squamous NSCLC; PLUS carboplatin IV (on Day 1 of each cycle) or cisplatin IV (on Day 1 of each cycle) for 4 cycles and pemetrexed IV (on Day 1 of each cycle) until progression, intolerable adverse events, or participant/physician decision for Non-squamous. | 366 |
| Pembrolizumab + Chemotherapy Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each cycle (cycle length = 3 weeks) for up to 35 cycles (up to \
2 years) PLUS paclitaxel IV (on Day 1 of each cycle) OR nab-paclitaxel IV (on Days 1, 8, and 15 of each cycle) and carboplatin IV (on Day 1 of each cycle) for 4 cycles for Squamous NSCLC; PLUS carboplatin IV (on Day 1 of each cycle) or cisplatin IV (on Day 1 of each cycle) for 4 cycles and pemetrexed IV (on Day 1 of each cycle) until progression, intolerable adverse events, or participant/physician decision for Non-squamous. | 373 |
| Total | 739 |
Baseline characteristics
| Characteristic | Pembrolizumab + Chemotherapy | Total | MK-7684A + Chemotherapy |
|---|---|---|---|
| Age, Continuous | 64.3 Years STANDARD_DEVIATION 8.9 | 64.3 Years STANDARD_DEVIATION 8.6 | 64.3 Years STANDARD_DEVIATION 8.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 92 Participants | 190 Participants | 98 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 249 Participants | 480 Participants | 231 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 32 Participants | 69 Participants | 37 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 22 Participants | 50 Participants | 28 Participants |
| Race (NIH/OMB) Asian | 131 Participants | 256 Participants | 125 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 14 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 13 Participants | 8 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 210 Participants | 406 Participants | 196 Participants |
| Sex: Female, Male Female | 121 Participants | 219 Participants | 98 Participants |
| Sex: Female, Male Male | 252 Participants | 520 Participants | 268 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 190 / 366 | 193 / 373 |
| other Total, other adverse events | 349 / 360 | 352 / 368 |
| serious Total, serious adverse events | 205 / 360 | 180 / 368 |
Outcome results
Primary
Overall Survival (OS) in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥1%
OS is defined as the time from the date of randomization to death due to any cause. The OS is reported for all participants with PD-L1 positive tumors (PD-L1 TPS≥1%). The OS was calculated using the product-limit (Kaplan-Meier) method for censored data.
Time frame: Up to approximately 29 months
Population: The analysis population includes all randomized participants with PD-L1 TPS≥1%. Participants were analyzed in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MK-7684A + Chemotherapy | Overall Survival (OS) in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥1% | 19.4 Months |
| Pembrolizumab + Chemotherapy | Overall Survival (OS) in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥1% | 23.5 Months |
p-value: 0.833595% CI: [0.87, 1.5]Log Rank
Secondary
Change From Baseline for Role Functioning (Items 6 and 7) Combined Score on the EORTC QLQ-C30
Change from baseline in the score of EORTC QLQ-C30 Items 6-7 was planned to be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 2 questions about their role functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a worse level of function.
Time frame: Baseline and up to approximately 29 months
Population: After additional Futility Analysis of OS was performed before the first efficacy analysis, as per the supplemental Statistical Analysis Plan amendment (effective date: September 16, 2025) it was stated that no further efficacy analyses would be performed, so the originally planned ePRO data are unavailable.
Secondary
Change From Baseline in Chest Pain Score (Item 40) on the EORTC QLQ- LC13
Change from baseline in the score of EORTC QLQ-LC13 Item 40 was planned to be presented. The EORTC QLQ-LC13 is a lung cancer specific health-related quality-of life (QoL) questionnaire. Participant response to the question Have you had pain in your chest? is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of chest pain.
Time frame: Baseline and Up to approximately 29 months
Population: After additional Futility Analysis of OS was performed before the first efficacy analysis, as per the supplemental Statistical Analysis Plan amendment (effective date: September 16, 2025) it was stated that no further efficacy analyses would be performed, so the originally planned ePRO data are unavailable.
Secondary
Change From Baseline in Cough Score (Item 31) on the European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-LC13)
Change from baseline in the score of EORTC QLQ-LC13 Item 31 was planned to be presented. The EORTC QLQ-LC13 is a lung cancer specific health-related quality-of life (QoL) questionnaire. Participant response to the question Have you coughed? is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates more frequent coughing.
Time frame: Baseline and Up to approximately 29 months
Population: After additional Futility Analysis of OS was performed before the first efficacy analysis, as per the supplemental Statistical Analysis Plan amendment (effective date: September 16, 2025) it was stated that no further efficacy analyses would be performed, so the originally planned ePRO data are unavailable.
Secondary
Change From Baseline in Dyspnea Score (Item 8) on the EORTC QLQ-C30
Change from baseline in the score of EORTC QLQ-C30 Item 8 was planned to be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant response to the question Were you short of breath? is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of dyspnea.
Time frame: Baseline and Up to approximately 29 months
Population: After additional Futility Analysis of OS was performed before the first efficacy analysis, as per the supplemental Statistical Analysis Plan amendment (effective date: September 16, 2025) it was stated that no further efficacy analyses would be performed, so the originally planned ePRO data are unavailable.
Secondary
Change From Baseline in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30
Change from baseline in the score of EORTC QLQ-C30 Items 1-5 was planned to be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a worse level of function.
Time frame: Baseline and Up to approximately 29 months
Population: After additional Futility Analysis of OS was performed before the first efficacy analysis, as per the supplemental Statistical Analysis Plan amendment (effective date: September 16, 2025) it was stated that no further efficacy analyses would be performed, so the originally planned ePRO data are unavailable.
Secondary
Change From Baseline in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
Change from baseline in the score of EORTC QLQ-C30 Items 29 and 30 was planned to be presented. The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to Items 29 and 30 (How would you rate your overall health during the past week? and How would you rate your overall quality of life during the past week?) are scored on a 7-point scale (1=Very Poor to 7=Excellent). A higher score indicates a better overall outcome.
Time frame: Baseline and Up to approximately 29 months
Population: After additional Futility Analysis of OS was performed before the first efficacy analysis, as per the supplemental Statistical Analysis Plan amendment (effective date: September 16, 2025) it was stated that no further efficacy analyses would be performed, so the originally planned electronic patient-reported outcome (ePRO) data are unavailable.
Secondary
Duration of Response (DOR)
For participants who demonstrate a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The DOR as assessed by BICR was planned to be presented.
Time frame: Up to approximately 29 months
Population: After additional Futility Analysis of OS was performed before the first efficacy analysis, as per the supplemental Statistical Analysis Plan amendment (effective date: September 16, 2025) it was stated that no further efficacy analyses would be performed, so the originally planned DOR data are unavailable.
Secondary
Number of Participants Who Discontinued Study Intervention Due to an AE
The number of participants who discontinue study intervention due to an adverse event (AE) will be presented. An AE is defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment.
Time frame: Up to approximately 46 months
Secondary
Number of Participants Who Experienced One or More Adverse Events (AEs)
The number of participants who experienced an adverse event (AE) will be presented. An AE is defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment.
Time frame: Up to approximately 46 months
Secondary
Objective Response Rate (ORR)
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by blinded independent central review (BICR) was planned to be presented.
Time frame: Up to approximately 29 months
Population: After additional Futility Analysis of OS was performed before the first efficacy analysis, as per the supplemental Statistical Analysis Plan amendment (effective date: September 16, 2025) it was stated that no further efficacy analyses would be performed, so the originally planned ORR data are unavailable.
Secondary
Overall Survival (OS) in All Participants
OS is defined as the time from the date of randomization to death due to any cause. The OS is reported for all randomized participants. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data.
Time frame: Up to approximately 29 months
Population: The analysis population includes all randomized participants. Participants were analyzed in the treatment group to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MK-7684A + Chemotherapy | Overall Survival (OS) in All Participants | 20.0 Months |
| Pembrolizumab + Chemotherapy | Overall Survival (OS) in All Participants | 19.7 Months |
p-value: 0.510495% CI: [0.82, 1.23]Log Rank
Secondary
Progression-Free Survival (PFS)
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1). PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review (BICR) was planned to be presented.
Time frame: Up to approximately 29 months
Population: After additional Futility Analysis of OS was performed before the first efficacy analysis, as per the supplemental Statistical Analysis Plan amendment (effective date: September 16, 2025) it was stated that no further efficacy analyses would be performed, so the originally planned PFS data are unavailable.
Secondary
Time to Deterioration (TTD) in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the EORTC QLQ-C30
TTD in the score of EORTC QLQ-C30 Items 29 and 30 was planned to be presented. The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to Items 29 and 30 (How would you rate your overall health during the past week? and How would you rate your overall quality of life during the past week?) are scored on a 7-point scale (1=Very Poor to 7=Excellent). A higher score indicates a better overall outcome. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline.
Time frame: Up to approximately 29 months
Population: After additional Futility Analysis of OS was performed before the first efficacy analysis, as per the supplemental Statistical Analysis Plan amendment (effective date: September 16, 2025) it was stated that no further efficacy analyses would be performed, so the originally planned ePRO data are unavailable.
Secondary
TTD in Chest Pain Score (Item 40) on the EORTC QLQ-LC13
TTD in the score of EORTC QLQ-LC13 Item 40 was planned to be presented. The EORTC QLQ-LC13 is a lung cancer specific health-related quality-of life (QoL) questionnaire. Participant response to the question Have you had pain in your chest? is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of chest pain. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline.
Time frame: Up to approximately 29 months
Population: After additional Futility Analysis of OS was performed before the first efficacy analysis, as per the supplemental Statistical Analysis Plan amendment (effective date: September 16, 2025) it was stated that no further efficacy analyses would be performed, so the originally planned ePRO data are unavailable.
Secondary
TTD in Cough Score (Item 31) on the EORTC QLQ-LC13
TTD in the score of EORTC QLQ-LC13 Item 31 was planned to be presented. The EORTC QLQ-LC13 is a lung cancer specific health-related quality-of life (QoL) questionnaire. Participant response to the question Have you coughed? is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates more frequent coughing. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline.
Time frame: Up to approximately 29 months
Population: After additional Futility Analysis of OS was performed before the first efficacy analysis, as per the supplemental Statistical Analysis Plan amendment (effective date: September 16, 2025) it was stated that no further efficacy analyses would be performed, so the originally planned ePRO data are unavailable.
Secondary
TTD in Dyspnea Score (Item 8) on the EORTC QLQ-C30
TTD in the score of EORTC QLQ-C30 Item 8 was planned to be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant response to the question Were you short of breath? is scored on a 4-point scale (1=Not at All to 4=Very Much). A higher score indicates a worse level of dyspnea. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline.
Time frame: Up to approximately 29 months
Population: After additional Futility Analysis of OS was performed before the first efficacy analysis, as per the supplemental Statistical Analysis Plan amendment (effective date: September 16, 2025) it was stated that no further efficacy analyses would be performed, so the originally planned ePRO data are unavailable.
Secondary
TTD in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ- C30
TTD in the score of EORTC QLQ-C30 Items 1-5 was planned to be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a worse level of function. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline.
Time frame: Up to approximately 29 months
Population: After additional Futility Analysis of OS was performed before the first efficacy analysis, as per the supplemental Statistical Analysis Plan amendment (effective date: September 16, 2025) it was stated that no further efficacy analyses would be performed, so the originally planned ePRO data are unavailable.
Secondary
TTD in Role Functioning (Items 6 and 7) Combined Score on the EORTC QLQ-C30
TTD in the score of EORTC QLQ-C30 Items 6-7 was planned to be presented. The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 2 questions about their role functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a worse level of function. TTD is defined as the time to first onset of 10 or more (out of 100) deterioration from baseline and confirmed by a second adjacent 10 or more deterioration from baseline.
Time frame: Up to approximately 29 months
Population: After additional Futility Analysis of OS was performed before the first efficacy analysis, as per the supplemental Statistical Analysis Plan amendment (effective date: September 16, 2025) it was stated that no further efficacy analyses would be performed, so the originally planned ePRO data are unavailable.