Non-small Cell Lung Cancer
Conditions
Keywords
PD1, PD-1, PDL1, PD-L1
Brief summary
The purpose of this study is to evaluate the efficacy and safety of pemetrexed plus platinum chemotherapy (carboplatin or cisplatin) with or without pembrolizumab (MK-3475; KEYTRUDA®) in the treatment of adults with the following types of tyrosine kinase inhibitor (TKI)-resistant, epidermal growth factor receptor (EGFR)-mutated, metastatic non-squamous non-small cell lung cancer (NSCLC) tumors: 1) TKI-failures (including osimertinib \[TAGRISSO®\] failure) with T790M-negative mutation tumors, 2) T790M-positive mutation tumors with prior exposure to osimertinib, and 3) first-line osimertinib failure regardless of T790M mutation status. The primary study hypotheses are that the combination of pembrolizumab plus chemotherapy has superior efficacy compared to saline placebo plus chemotherapy in terms of: 1) Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) based on blinded independent central review, and 2) Overall Survival (OS). This study will be considered to have met its success criteria if the combination of pembrolizumab plus chemotherapy is superior to saline placebo plus chemotherapy in terms of PFS or OS. Upon study completion, participants are discontinued and may be enrolled in a pembrolizumab extension study, if available.
Interventions
BIOLOGICALpembrolizumab
IV infusion
DRUGpemetrexed
IV infusion
DRUGcarboplatin
IV infusion
DRUGcisplatin
IV infusion
DRUGsaline solution
IV infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed diagnosis of Stage IV non-squamous NSCLC. * Documentation of tumor activating EGFR mutation, specifically either DEL19 or L858R. * Investigator-determined radiographic disease progression per RECIST 1.1 after treatment with an EGFR TKI therapy: a) Participants previously treated with 1st or 2nd generation EGFR TKI (e.g. erlotinib/afatinib/gefitinib) are required to have confirmed documented absence of EGFR T790M mutation; b) Participants with confirmed acquired T790M mutation after 1st or 2nd generation EGFR TKI (e.g. erlotinib/afatinib/gefitinib) are required to have osimertinib TKI treatment failure prior to enrollment; c) Participants previously failed osimertinib TKI treatment as 1st line therapy are eligible regardless of their EGFR T790M mutation status. Note: TKI washout period for all participants is 1 week or 2 half-lives after last treatment dose, whichever is longer. TKI washout should be completed prior to first dose of study treatment. * Measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. * Provided archival tumor tissue sample or newly obtained (no anti-neoplastic therapy since biopsy) core or excisional biopsy of a tumor lesion not previously irradiated. * Life expectancy of at least 3 months. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of study treatment but before randomization. * Male participants must agree to use contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab and up to 180 days after last dose of chemotherapeutic agents. * Female participants must not be pregnant, not breastfeeding, and must agree to use contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab and up to 180 days after the last dose of chemotherapeutic agents. * Adequate organ function.
Exclusion criteria
* Predominantly squamous cell histology NSCLC. Mixed tumors will be categorized by the predominant cell type; if small cell elements are present, the participant is ineligible. * Symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible. * Received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein-4 \[CTLA-4\], OX-40, CD137). * Received prior systemic cytotoxic chemotherapy or investigational agent(s), excluding EGFR TKIs, for metastatic NSCLC. \[Notes: 1) Prior treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic NSCLC. 2) If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. 3) Prior exposure to traditional medicine(s) is allowed as long as therapy was discontinued at least 4 weeks prior to the first dose of study treatment.\] * Received prior radiotherapy within 2 weeks of start of study treatment or has received lung radiation therapy of \>30 Gray (Gy) within 6 months before the first dose of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease. * Received a live vaccine within 30 days prior to the first dose of study treatment. * Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. * Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment. * Known additional malignancy that is progressing or has required active treatment within the past 5 years. (Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.) * Known active untreated CNS metastases and/or carcinomatous meningitis. * Severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients. * Known sensitivity to any component of cisplatin, carboplatin, or pemetrexed. * Active autoimmune disease that has required systemic treatment in past 2 years. * History of (non-infectious) pneumonitis that required steroids or has current pneumonitis. * Active infection requiring systemic therapy. * Known history of human immunodeficiency virus (HIV) infection. * Known history of Hepatitis B or known active Hepatitis C virus. * Known history of active tuberculosis (TB; Bacillus tuberculosis) * Pregnant, breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of pembrolizumab and up to 180 days after the last dose of chemotherapeutic agents.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | Up to ~40 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. PFS was assessed by blinded independent central review (BICR) using RECIST 1.1. Per RECIST 1.1, PD is defined as at least a 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. Note: The appearance of one or more new lesions is also considered PD. The PFS presented was analyzed using the product-limit (Kaplan-Meier) method for censored data. |
| Overall Survival (OS) | Up to ~51 months | OS is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis will be censored at the date of the last follow-up. The OS presented was analyzed using the product-limit (Kaplan-Meier) method for censored data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score | Baseline and Week 18 | The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions regarding Global Health Status (GHS; How would you rate your overall health during the past week?) and Quality of Life (QoL; How would you rate your overall quality of life during the past week?) are each scored on a 7-point scale (1=Very poor to 7=Excellent). The two raw scores were averaged into a combined score, then normalized using linear transformation so each participant's score ranged from 0 to 100 (0=Worst overall health/quality of life and 100=Best overall health/quality of life). The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score is presented. |
| Time to True Deterioration (TTD) in the EORTC Questionnaire Composite Endpoint of Cough, Chest Pain or Dyspnea | Baseline and up to ~51 months | TTD is the time from baseline to first onset of 10 points or more deterioration from baseline with confirmation by the subsequent visit of 10 points or more deterioration from baseline in the composite endpoint of cough \[EORTC QLQ-Lung Cancer Module 13 (LC13) Item 1; How much did you cough?\], chest pain \[EORTC QLQ-LC13 Item 10; Have you had pain in your chest?\], or dyspnea \[EORTC QLQ-C30 Item 8; Were you short of breath?\]. Individual responses are given on a 4-point scale (1=Not at all; 4=Very much), with a lower score indicating a better outcome. The TTD was analyzed using the product-limit (Kaplan-Meier) method for censored data. The time to true deterioration in the composite endpoint of cough, chest pain or dyspnea is presented. |
| Objective Response Rate (ORR) Per RECIST 1.1 | Up to ~51 months | ORR was assessed by BICR using RECIST 1.1. ORR is defined as the percentage of participants in the analysis population who experience a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The ORR for participants is presented. |
| Percentage of Participants Who Discontinued Study Treatment Due to AEs | Up to ~41 months | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. The percentage of participants who discontinued study treatment due to an adverse event is presented. |
| Percentage of Participants Who Experienced an Adverse Event (AE) | Up to ~44 months | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. The percentage of participants who experienced an AE is presented. |
| Duration of Response (DOR) Per RECIST 1.1 | Up to ~51 months | DOR was assessed by BICR using RECIST 1.1. For participants who experience a response of CR or PR, DOR is defined as the time from the earliest date of qualifying response until earliest date of PD or death from any cause, whichever comes first. The DOR presented was analyzed using the product-limit (Kaplan-Meier) method for censored data. |
Countries
Australia, Brazil, Canada, China, France, Germany, Hong Kong, Israel, Italy, Japan, Mexico, South Korea, Spain, Sweden, Taiwan, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pembro + Pemetrexed + Chemo Participants received pembrolizumab (pembro) 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W with no restrictions on the number of cycles PLUS platinum chemotherapy (chemo) (either carboplatin Area Under the Curve \[AUC\] 5 via IV infusion Q3W for 4 cycles \[Cycles 1-4\] or cisplatin 75 mg/m\^2 via IV infusion Q3W for 4 cycles \[Cycles 1-4\]). | 245 |
| Placebo + Pemetrexed + Chemo Participants received normal saline solution via IV infusion on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W with no restrictions on the number of cycles PLUS platinum chemotherapy (chemo)(either carboplatin AUC 5 via IV infusion Q3W for 4 cycles \[Cycles 1-4\] or cisplatin 75 mg/m\^2 via IV infusion Q3W for 4 cycles \[Cycles 1-4\]). Eligible participants who had BICR-verified progressive disease were eligible to switch over to pembrolizumab monotherapy 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) for up to 35 cycles. | 247 |
| Total | 492 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 219 | 227 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Participation Was Terminated By Sponsor | 26 | 15 |
| Overall Study | Withdrawal by Subject | 0 | 4 |
Baseline characteristics
| Characteristic | Pembro + Pemetrexed + Chemo | Placebo + Pemetrexed + Chemo | Total |
|---|---|---|---|
| Age, Continuous | 61.7 Years STANDARD_DEVIATION 10.9 | 63.1 Years STANDARD_DEVIATION 10 | 62.4 Years STANDARD_DEVIATION 10.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 19 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 222 Participants | 221 Participants | 443 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 7 Participants | 14 Participants |
| Geographic Region East Asia | 150 Count of Participants | 150 Count of Participants | 300 Count of Participants |
| Geographic Region EU | 53 Count of Participants | 47 Count of Participants | 100 Count of Participants |
| Geographic Region Non-East Asia | 95 Count of Participants | 97 Count of Participants | 192 Count of Participants |
| Geographic Region Non-EU | 192 Count of Participants | 200 Count of Participants | 392 Count of Participants |
| Geographic Region Non-US | 242 Count of Participants | 241 Count of Participants | 483 Count of Participants |
| Geographic Region US | 3 Count of Participants | 6 Count of Participants | 9 Count of Participants |
| Previous use of Tyrosine Kinase Inhibitor (TKI) Treatment History with Osimertinib Other | 1 Count of Participants | 0 Count of Participants | 1 Count of Participants |
| Previous use of Tyrosine Kinase Inhibitor (TKI) Treatment History with Osimertinib Treated with first line Osimertinib | 28 Count of Participants | 33 Count of Participants | 61 Count of Participants |
| Previous use of Tyrosine Kinase Inhibitor (TKI) Treatment History with Osimertinib Treated with second line Osimertinib | 88 Count of Participants | 88 Count of Participants | 176 Count of Participants |
| Previous use of Tyrosine Kinase Inhibitor (TKI) Treatment History with Osimertinib Treated with TKI except for Osimertinib | 128 Count of Participants | 126 Count of Participants | 254 Count of Participants |
| Programmed Death Ligand 1 (PD-L1) Status Not evaluable | 12 Count of Participants | 11 Count of Participants | 23 Count of Participants |
| Programmed Death Ligand 1 (PD-L1) Status TPS <1% | 127 Count of Participants | 113 Count of Participants | 240 Count of Participants |
| Programmed Death Ligand 1 (PD-L1) Status TPS ≥1% AND ≤49% | 54 Count of Participants | 72 Count of Participants | 126 Count of Participants |
| Programmed Death Ligand 1 (PD-L1) Status TPS <50% | 181 Count of Participants | 185 Count of Participants | 366 Count of Participants |
| Programmed Death Ligand 1 (PD-L1) Status TPS ≥ 50% | 52 Count of Participants | 51 Count of Participants | 103 Count of Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Asian | 165 Participants | 163 Participants | 328 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 5 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 4 Participants | 11 Participants |
| Race (NIH/OMB) White | 67 Participants | 72 Participants | 139 Participants |
| Sex: Female, Male Female | 152 Participants | 151 Participants | 303 Participants |
| Sex: Female, Male Male | 93 Participants | 96 Participants | 189 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 219 / 245 | 186 / 247 | 44 / 50 |
| other Total, other adverse events | 233 / 245 | 225 / 246 | 31 / 50 |
| serious Total, serious adverse events | 86 / 245 | 70 / 246 | 8 / 50 |
Outcome results
Primary
Overall Survival (OS)
OS is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis will be censored at the date of the last follow-up. The OS presented was analyzed using the product-limit (Kaplan-Meier) method for censored data.
Time frame: Up to ~51 months
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembro + Pemetrexed + Chemo | Overall Survival (OS) | 15.9 Months |
| Placebo + Pemetrexed + Chemo | Overall Survival (OS) | 14.7 Months |
p-value: 0.036295% CI: [0.69, 1.02]Log Rank
Primary
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. PFS was assessed by blinded independent central review (BICR) using RECIST 1.1. Per RECIST 1.1, PD is defined as at least a 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. Note: The appearance of one or more new lesions is also considered PD. The PFS presented was analyzed using the product-limit (Kaplan-Meier) method for censored data.
Time frame: Up to ~40 months
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembro + Pemetrexed + Chemo | Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 5.6 Months |
| Placebo + Pemetrexed + Chemo | Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 5.5 Months |
p-value: 0.012295% CI: [0.65, 0.97]Log Rank
Secondary
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score
The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions regarding Global Health Status (GHS; How would you rate your overall health during the past week?) and Quality of Life (QoL; How would you rate your overall quality of life during the past week?) are each scored on a 7-point scale (1=Very poor to 7=Excellent). The two raw scores were averaged into a combined score, then normalized using linear transformation so each participant's score ranged from 0 to 100 (0=Worst overall health/quality of life and 100=Best overall health/quality of life). The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score is presented.
Time frame: Baseline and Week 18
Population: All randomized participants who had at least 1 patient reported outcome (PRO) assessment available and had received at least 1 dose of study intervention
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembro + Pemetrexed + Chemo | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score | -0.46 Score on a Scale |
| Placebo + Pemetrexed + Chemo | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score | -2.05 Score on a Scale |
95% CI: [-1.93, 5.1]
Secondary
Duration of Response (DOR) Per RECIST 1.1
DOR was assessed by BICR using RECIST 1.1. For participants who experience a response of CR or PR, DOR is defined as the time from the earliest date of qualifying response until earliest date of PD or death from any cause, whichever comes first. The DOR presented was analyzed using the product-limit (Kaplan-Meier) method for censored data.
Time frame: Up to ~51 months
Population: All randomized participants that had a response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembro + Pemetrexed + Chemo | Duration of Response (DOR) Per RECIST 1.1 | 6.3 Months |
| Placebo + Pemetrexed + Chemo | Duration of Response (DOR) Per RECIST 1.1 | 5.6 Months |
Secondary
Objective Response Rate (ORR) Per RECIST 1.1
ORR was assessed by BICR using RECIST 1.1. ORR is defined as the percentage of participants in the analysis population who experience a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The ORR for participants is presented.
Time frame: Up to ~51 months
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembro + Pemetrexed + Chemo | Objective Response Rate (ORR) Per RECIST 1.1 | 29.0 Percentage of Participants |
| Placebo + Pemetrexed + Chemo | Objective Response Rate (ORR) Per RECIST 1.1 | 27.1 Percentage of Participants |
95% CI: [-6, 9.9]
Secondary
Percentage of Participants Who Discontinued Study Treatment Due to AEs
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. The percentage of participants who discontinued study treatment due to an adverse event is presented.
Time frame: Up to ~41 months
Population: All randomized participants who received at least 1 dose of study intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembro + Pemetrexed + Chemo | Percentage of Participants Who Discontinued Study Treatment Due to AEs | 19.2 Percentage of Participants |
| Placebo + Pemetrexed + Chemo | Percentage of Participants Who Discontinued Study Treatment Due to AEs | 17.1 Percentage of Participants |
Secondary
Percentage of Participants Who Experienced an Adverse Event (AE)
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. The percentage of participants who experienced an AE is presented.
Time frame: Up to ~44 months
Population: All randomized participants who received at least 1 dose of study intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembro + Pemetrexed + Chemo | Percentage of Participants Who Experienced an Adverse Event (AE) | 97.6 Percentage of Participants |
| Placebo + Pemetrexed + Chemo | Percentage of Participants Who Experienced an Adverse Event (AE) | 98.0 Percentage of Participants |
Secondary
Time to True Deterioration (TTD) in the EORTC Questionnaire Composite Endpoint of Cough, Chest Pain or Dyspnea
TTD is the time from baseline to first onset of 10 points or more deterioration from baseline with confirmation by the subsequent visit of 10 points or more deterioration from baseline in the composite endpoint of cough \[EORTC QLQ-Lung Cancer Module 13 (LC13) Item 1; How much did you cough?\], chest pain \[EORTC QLQ-LC13 Item 10; Have you had pain in your chest?\], or dyspnea \[EORTC QLQ-C30 Item 8; Were you short of breath?\]. Individual responses are given on a 4-point scale (1=Not at all; 4=Very much), with a lower score indicating a better outcome. The TTD was analyzed using the product-limit (Kaplan-Meier) method for censored data. The time to true deterioration in the composite endpoint of cough, chest pain or dyspnea is presented.
Time frame: Baseline and up to ~51 months
Population: All randomized participants who had at least 1 PRO assessment available and had received at least 1 dose of study intervention
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembro + Pemetrexed + Chemo | Time to True Deterioration (TTD) in the EORTC Questionnaire Composite Endpoint of Cough, Chest Pain or Dyspnea | NA Months |
| Placebo + Pemetrexed + Chemo | Time to True Deterioration (TTD) in the EORTC Questionnaire Composite Endpoint of Cough, Chest Pain or Dyspnea | 17.97 Months |
95% CI: [0.68, 1.27]