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NCT03976323

Study of Pembrolizumab With Maintenance Olaparib or Maintenance Pemetrexed in First-line (1L) Metastatic Nonsquamous Non-Small-Cell Lung Cancer (NSCLC) (MK-7339-006, KEYLYNK-006)

Completed Phase 3 Results posted Last updated 25 February 2026
What this trial tests

Phase 3 trial testing Pembrolizumab in Carcinoma, Nonsquamous Non-small-cell Lung in 1,003 participants. Completed in 29 January 2026.

Timeline
28 June 2019
Primary endpoint
7 February 2024
29 January 2026

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment1,003
Start date28 June 2019
Primary completion7 February 2024
Estimated completion29 January 2026
Sites178 locations across Colombia, Japan, Taiwan, Poland, South Korea, New Zealand, Russia, United States

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Carcinoma, Nonsquamous Non-small-cell Lung. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression-free Survival (PFS) Primary · Up to ~31 months

PFS was defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) based on blinded independent central review (BICR) or death due to any cause, whichever occurs first. PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS was analyzed by the non-parametric Kaplan-Meier (K-M) method. The proto

GroupValue95% CI
Pembrolizumab + Olaparib (Maintenance Phase)7.15.6 – 8.7
Pembrolizumab + Pemetrexed (Maintenance Phase)8.36.9 – 11.5
Overall Survival (OS) Primary · Up to ~51 months

OS was defined as the time from randomization to death due to any cause. OS was analyzed by the non-parametric K-M method. Participants without documented death at the time of analyses were censored at the date of last known to be alive. The protocol specified final analysis of OS is presented here for the first pembrolizumab course in the Maintenance Phase. Per protocol, analysis for this outcome measure was not planned or conducted in the Induction Phase.

GroupValue95% CI
Pembrolizumab + Olaparib (Maintenance Phase)20.718.0 – 24.8
Pembrolizumab + Pemetrexed (Maintenance Phase)23.019.0 – 26.4
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status / Quality of Life (Items 29 and 30) Scale Score Secondary · Baseline and Week 24

EORTC QLQ-C30 is a questionnaire to assess the overall quality of life (QoL) of cancer patients. Participant responses to questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and QoL ("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). The combined score of GHS (Item 29) and QoL (Item 30) is computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores range from

GroupValue95% CI
Pembrolizumab + Olaparib (Maintenance Phase)-5.34-7.78 – -2.90
Pembrolizumab + Pemetrexed (Maintenance Phase)-3.44-5.90 – -0.98
Time to True Deterioration (TTD) in EORTC QLQ-C30 Global Health Status / Quality of Life (Items 29 & 30) Scale Score Secondary · Up to ~24 months

EORTC QLQ-C30 is a questionnaire to assess QoL of cancer patients. Participant responses to questions on GHS ("How would you rate your overall health during the past week?") and QoL ("How would you rate your overall QoL during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) is computed by averaging raw scores of the 2 items and applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. TTD is defined as the time fro

GroupValue95% CI
Pembrolizumab + Olaparib (Maintenance Phase)19.8115.97 – NA
Pembrolizumab + Pemetrexed (Maintenance Phase)17.289.46 – NA
Change From Baseline in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score Secondary · Baseline and Week 24

EORTC QLQ-LC13 is a lung cancer specific questionnaire. Participant responses to the question regarding cough (Item 1): "How much did you cough?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0-100. A lower score indicates a better outcome. The change from baseline in EORTC QLQ-LC13 cough (Item 1) score is presented. The protocol specified final analysis for the first pembrolizumab course in the Maintenance Phase is reported. Per protocol, analysis for this outcome measure was not planned or cond

GroupValue95% CI
Pembrolizumab + Olaparib (Maintenance Phase)-1.98-4.90 – 0.94
Pembrolizumab + Pemetrexed (Maintenance Phase)-1.82-4.77 – 1.12
TTD in EORTC QLQ-LC13 Cough (Item 1) Scale Score Secondary · Up to ~24 months

EORTC QLQ-LC13 is a lung cancer specific questionnaire. Participant responses to the question regarding cough (Item 1): "How much did you cough?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0-100. A lower score indicates a better outcome. TTD is defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in cough (Item 1). TTD estimated by non-parametric K-M method is presented here. A longer TTD indicates a better outcome. The protocol specified final

GroupValue95% CI
Pembrolizumab + Olaparib (Maintenance Phase)NANA – NA
Pembrolizumab + Pemetrexed (Maintenance Phase)NANA – NA
Change From Baseline in EORTC QLQ-LC13 Chest Pain (Item 10) Scale Score Secondary · Baseline and Week 24

EORTC QLQ-LC13 is a lung cancer specific questionnaire. Participant responses to the question regarding chest pain (Item 10): "Have you had pain in your chest?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. The change from baseline in EORTC QLQ-LC13 chest pain (Item 10) score is presented. The protocol specified final analysis for the first pembrolizumab course in the Maintenance Phase is reported. Per protocol, analysis for this outcome measure

GroupValue95% CI
Pembrolizumab + Olaparib (Maintenance Phase)-0.82-3.25 – 1.61
Pembrolizumab + Pemetrexed (Maintenance Phase)-0.47-2.92 – 1.98
TTD in EORTC QLQ-LC13 Chest Pain (Item 10) Scale Score Secondary · Up to ~24 months

EORTC QLQ-LC13 is a lung cancer specific questionnaire. Participant responses to the question regarding chest pain (Item 10): "Have you had pain in your chest?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. TTD is defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in chest pain (Item 10). TTD estimated by non-parametric K-M method is presented here. A longer TTD indicates a better outcome. The

GroupValue95% CI
Pembrolizumab + Olaparib (Maintenance Phase)NANA – NA
Pembrolizumab + Pemetrexed (Maintenance Phase)NANA – NA
Change From Baseline in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score Secondary · Baseline and Week 24

EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to the question regarding dyspnea (Item 8): "Were you short of breath?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. The change from baseline in EORTC QLQ-C30 dyspnea (Item 8) score is presented. The protocol specified final analysis for the first pembrolizumab course in Maintenance Phase is reported. Per protocol, analysis for this outcome meas

GroupValue95% CI
Pembrolizumab + Olaparib (Maintenance Phase)-0.16-3.07 – 2.76
Pembrolizumab + Pemetrexed (Maintenance Phase)1.35-1.60 – 4.31
TTD in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score Secondary · Up to ~24 months

EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to the question regarding dyspnea (Item 8): "Were you short of breath?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. TTD is defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in dyspnea (Item 8). TTD estimated by non-parametric K-M method is presented here. A longer TTD indicates a better outco

GroupValue95% CI
Pembrolizumab + Olaparib (Maintenance Phase)NANA – NA
Pembrolizumab + Pemetrexed (Maintenance Phase)NANA – NA
Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score Secondary · Baseline and Week 24

EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning (Items 1 to 5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 is computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. The change from baseline in EORTC QLQ-C30 physical functioning (Items 1-5) combined score is presented. The protocol spe

GroupValue95% CI
Pembrolizumab + Olaparib (Maintenance Phase)-2.79-4.92 – -0.65
Pembrolizumab + Pemetrexed (Maintenance Phase)-2.78-4.93 – -0.62
TTD in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score Secondary · Up to ~24 months

EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning (Items 1 to 5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 is computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. TTD is defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in physica

GroupValue95% CI
Pembrolizumab + Olaparib (Maintenance Phase)20.9613.34 – NA
Pembrolizumab + Pemetrexed (Maintenance Phase)NA17.28 – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to ~51 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pembrolizumab + Pemetrexed + Platinum Therapy (Induction Phase)
Serious: 235/1003 (23%)
Deaths: 116/1003
Pembrolizumab (First Course) + Olaparib (Maintenance Phase)
Serious: 118/337 (35%)
Deaths: 233/337
Pembrolizumab (First Course) + Pemetrexed (Maintenance Phase)
Serious: 125/332 (38%)
Deaths: 233/335
Pembrolizumab (Second Course) + Olaparib (Maintenance Phase)
Serious: 0/7 (0%)
Deaths: 0/7
Pembrolizumab (Second Course) + Pemetrexed (Maintenance Phase)
Serious: 1/13 (8%)
Deaths: 2/13

Serious adverse events (293 terms)

ReactionSystemPembrolizumab + Pemetrexed…Pembrolizumab (First Cours…Pembrolizumab (First Cours…Pembrolizumab (Second Cour…Pembrolizumab (Second Cour…
AnaemiaBlood and lymphatic system disorders
PneumoniaInfections and infestations
ThrombocytopeniaBlood and lymphatic system disorders
COVID-19 pneumoniaInfections and infestations
Febrile neutropeniaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
SepsisInfections and infestations
Pleural effusionRespiratory, thoracic and mediastinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders
DeathGeneral disorders
General physical health deteriorationGeneral disorders
LeukopeniaBlood and lymphatic system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
NauseaGastrointestinal disorders
COVID-19Infections and infestations
Acute kidney injuryRenal and urinary disorders
Urinary tract infectionInfections and infestations
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
Cardiac arrestCardiac disorders
DiarrhoeaGastrointestinal disorders
AstheniaGeneral disorders
Chest painGeneral disorders
ErysipelasInfections and infestations
Other adverse events (50 terms — click to expand)

ReactionSystemPembrolizumab + Pemetrexed…Pembrolizumab (First Cours…Pembrolizumab (First Cours…Pembrolizumab (Second Cour…Pembrolizumab (Second Cour…
AnaemiaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
LeukopeniaBlood and lymphatic system disorders
FatigueGeneral disorders
ThrombocytopeniaBlood and lymphatic system disorders
Alanine aminotransferase increasedInvestigations
AstheniaGeneral disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
RashSkin and subcutaneous tissue disorders
PyrexiaGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
Oedema peripheralGeneral disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Blood creatinine increasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
HeadacheNervous system disorders
HypothyroidismEndocrine disorders
DizzinessNervous system disorders
Blood alkaline phosphatase increasedInvestigations
HyperglycaemiaMetabolism and nutrition disorders
Weight decreasedInvestigations
Back painMusculoskeletal and connective tissue disorders
HypokalaemiaMetabolism and nutrition disorders
COVID-19Infections and infestations
Chest painGeneral disorders
DysgeusiaNervous system disorders
HyperkalaemiaMetabolism and nutrition disorders
HypertensionVascular disorders
HyponatraemiaMetabolism and nutrition disorders
Pain in extremityMusculoskeletal and connective tissue disorders
LymphopeniaBlood and lymphatic system disorders
MyalgiaMusculoskeletal and connective tissue disorders
Blood lactate dehydrogenase increasedInvestigations
HypoalbuminaemiaMetabolism and nutrition disorders

Most-reported serious reactions: Anaemia, Pneumonia, Thrombocytopenia, COVID-19 pneumonia, Febrile neutropenia, Neutropenia, Sepsis, Pleural effusion.

Data from ClinicalTrials.gov NCT03976323 adverse events section.

Sponsor's own description

The current study will compare pembrolizumab (MK-3475) plus maintenance olaparib, versus (vs) pembrolizumab plus maintenance pemetrexed for the treatment of non-squamous NSCLC. The study's 2 primary hypotheses are: 1. Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance pemetrexed with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by blinded independent clinical review (BICR) and 2. Pembrolizumab plus maintenance olaparib is superior to pembrolizumab plus maintenance pemetrexed with respect to overall survival (OS).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Immunotherapy in Lung Cancer: Current Landscape and Future Directions.
    Mamdani H, Matosevic S, Khalid AB, Durm G, et al · · 2022 · cited 253× · PMID 35222404 · DOI 10.3389/fimmu.2022.823618
  2. Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade.
    Genova C, Dellepiane C, Carrega P, Sommariva S, et al · · 2021 · cited 168× · PMID 35069581 · DOI 10.3389/fimmu.2021.799455
  3. Combined PARP Inhibition and Immune Checkpoint Therapy in Solid Tumors.
    Peyraud F, Italiano A. · · 2020 · cited 163× · PMID 32526888 · DOI 10.3390/cancers12061502
  4. Mechanisms of resistance to targeted therapy and immunotherapy in non-small cell lung cancer: promising strategies to overcoming challenges.
    Xiang Y, Liu X, Wang Y, Zheng D, et al · · 2024 · cited 85× · PMID 38655260 · DOI 10.3389/fimmu.2024.1366260
  5. Resistance to immune checkpoint inhibitors in non-small cell lung cancer: biomarkers and therapeutic strategies.
    Walsh RJ, Soo RA. · · 2020 · cited 77× · PMID 32670423 · DOI 10.1177/1758835920937902
  6. Targeting DNA Damage Repair for Immune Checkpoint Inhibition: Mechanisms and Potential Clinical Applications.
    Sun W, Zhang Q, Wang R, Li Y, et al · · 2021 · cited 44× · PMID 34026622 · DOI 10.3389/fonc.2021.648687
  7. The Mechanisms of PD-L1 Regulation in Non-Small-Cell Lung Cancer (NSCLC): Which Are the Involved Players?
    Lamberti G, Sisi M, Andrini E, Palladini A, et al · · 2020 · cited 38× · PMID 33114576 · DOI 10.3390/cancers12113129
  8. Developments in targeted therapy & immunotherapy-how non-small cell lung cancer management will change in the next decade: a narrative review.
    Li MSC, Mok KKS, Mok TSK. · · 2023 · cited 37× · PMID 37675321 · DOI 10.21037/atm-22-4444

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03976323.

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