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NCT02864394

Study of Pembrolizumab Versus Docetaxel in Participants Previously Treated for Non-Small Cell Lung Cancer (MK-3475-033/KEYNOTE-033)

Completed Phase 3 Results posted Last updated 19 September 2024
What this trial tests

Phase 3 trial testing Pembrolizumab in Carcinoma, Non-Small-Cell Lung in 425 participants. Completed in 14 October 2022.

Timeline
7 September 2016
Primary endpoint
9 September 2019
14 October 2022

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment425
Start date7 September 2016
Primary completion9 September 2019
Estimated completion14 October 2022

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Carcinoma, 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.

Overall Survival (OS) in Participants With Programmed Cell Death Ligand 1 (PD-L1) Positive (Tumor Proportion Score [TPS] ≥50%) Tumors Primary · Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS was reported by treatment arm for participants in the TPS ≥50% stratum of PD-L1 expression.

GroupValue95% CI
Pembrolizumab12.310.0 – 16.3
Docetaxel10.98.3 – 13.1
OS in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants) Primary · Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS was reported by treatment arm for participants in the TPS ≥1% stratum of PD-L1 expression (all participants).

GroupValue95% CI
Pembrolizumab12.910.3 – 16.5
Docetaxel10.68.7 – 12.5
Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With PD-L1 Positive (TPS ≥50%) Tumors Primary · Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters (SOD) of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS was reported by treatment arm for participants in the TPS ≥50% stratum of PD-L1 expression.

GroupValue95% CI
Pembrolizumab4.02.1 – 8.0
Docetaxel2.52.1 – 4.2
PFS Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants) Primary · Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the SOD of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS was reported by treatment arm for participants in the TPS ≥1% stratum of PD-L1 expression (all participants).

GroupValue95% CI
Pembrolizumab3.32.1 – 4.1
Docetaxel3.02.3 – 4.0
Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥50%) Tumors Secondary · Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by BICR. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for participants in the TPS ≥50% stratum of PD-L1 expression.

GroupValue95% CI
Pembrolizumab28.120.1 – 37.3
Docetaxel7.13.1 – 13.5
ORR Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants) Secondary · Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

ORR was defined as the percentage of participants in the analysis population who had a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by BICR. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for participants in the TPS ≥1% stratum of PD-L1 expression (all participants).

GroupValue95% CI
Pembrolizumab20.715.4 – 26.7
Docetaxel5.73.0 – 9.7
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥50%) Tumors Secondary · Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 based upon BICR, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, th

GroupValue95% CI
Pembrolizumab16.610.0 – NA
Docetaxel6.44.1 – NA
DOR Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants) Secondary · Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 based upon BICR, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, th

GroupValue95% CI
Pembrolizumab16.610.2 – NA
Docetaxel6.33.9 – NA
Number of Participants Who Experienced an Adverse Event (AE) Secondary · Up to approximately 66 months

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Per protocol, MedDRA

GroupValue95% CI
Pembrolizumab206
Docetaxel187
Number of Participants Who Discontinued Study Treatment Due to an AE Secondary · Up to approximately 45 months

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Per protocol, the num

GroupValue95% CI
Pembrolizumab32
Docetaxel24
Number of Participants Who Experienced an Adverse Event of Special Interest (AEOSI) Secondary · Up to approximately 66 months

An AEOSI was defined as any AE that is immune-mediated or potentially immune-mediated. An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally

GroupValue95% CI
Pembrolizumab63
Docetaxel12
Number of Participants Who Experienced a Grade 3-5 AE Secondary · Up to approximately 66 months

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Per protocol, MedDRA p

GroupValue95% CI
Pembrolizumab86
Docetaxel117

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 66 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pembrolizumab
Serious: 77/213 (36%)
Deaths: 182/213
Docetaxel
Serious: 75/198 (38%)
Deaths: 195/212
Pembrolizumab 2ⁿᵈ Course
Serious: 2/10 (20%)
Deaths: 3/10

Serious adverse events (91 terms)

ReactionSystemPembrolizumabDocetaxelPembrolizumab 2ⁿᵈ Course
PneumoniaInfections and infestations
Febrile neutropeniaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders
HaemoptysisRespiratory, thoracic and mediastinal disorders
Interstitial lung diseaseRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
LeukopeniaBlood and lymphatic system disorders
DeathGeneral disorders
FatigueGeneral disorders
Immune-mediated hepatitisHepatobiliary disorders
Upper respiratory tract infectionInfections and infestations
DyspnoeaRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
DysphagiaGastrointestinal disorders
Upper gastrointestinal haemorrhageGastrointestinal disorders
AppendicitisInfections and infestations
Infusion related reactionInjury, poisoning and procedural complications
Decreased appetiteMetabolism and nutrition disorders
HypercalcaemiaMetabolism and nutrition disorders
MalnutritionMetabolism and nutrition disorders
Other adverse events (58 terms — click to expand)

ReactionSystemPembrolizumabDocetaxelPembrolizumab 2ⁿᵈ Course
AnaemiaBlood and lymphatic system disorders
AlopeciaSkin and subcutaneous tissue disorders
White blood cell count decreasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
NeutropeniaBlood and lymphatic system disorders
Aspartate aminotransferase increasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
Weight decreasedInvestigations
HypoalbuminaemiaMetabolism and nutrition disorders
Alanine aminotransferase increasedInvestigations
FatigueGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
LeukopeniaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
RashSkin and subcutaneous tissue disorders
HaemoptysisRespiratory, thoracic and mediastinal disorders
DiarrhoeaGastrointestinal disorders
AstheniaGeneral disorders
HypothyroidismEndocrine disorders
Neutrophil count decreasedInvestigations
InsomniaPsychiatric disorders
Chest painGeneral disorders
HypokalaemiaMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
PneumoniaInfections and infestations
HyponatraemiaMetabolism and nutrition disorders
PyrexiaGeneral disorders
HyperglycaemiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
PruritusSkin and subcutaneous tissue disorders
HyperthyroidismEndocrine disorders
Blood alkaline phosphatase increasedInvestigations
Gamma-glutamyltransferase increasedInvestigations
VomitingGastrointestinal disorders
Oedema peripheralGeneral disorders
Blood cholesterol increasedInvestigations
Productive coughRespiratory, thoracic and mediastinal disorders
Upper respiratory tract infectionInfections and infestations
HypertriglyceridaemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Pneumonia, Febrile neutropenia, Neutropenia, Pneumonitis, Pyrexia, Haemoptysis, Interstitial lung disease, Pleural effusion.

Data from ClinicalTrials.gov NCT02864394 adverse events section.

Sponsor's own description

The purpose of this study is to assess the efficacy of pembrolizumab (MK-3475) versus docetaxel in participants with non-small cell lung cancer (NSCLC) with programmed cell death ligand 1 (PD-L1) positive tumors who have experienced disease progression after platinum-containing systemic therapy. The primary hypotheses of this study are that pembrolizumab (MK-3475) prolongs overall survival (OS) and that pembrolizumab prolongs progression-free survival (PFS), compared to docetaxel in participants with PD-L1 positive tumors.

Publications & conference data

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

  1. Immune checkpoint inhibitors: recent progress and potential biomarkers.
    Darvin P, Toor SM, Sasidharan Nair V, Elkord E. · · 2018 · cited 1495× · PMID 30546008 · DOI 10.1038/s12276-018-0191-1
  2. Current Clinical Progress of PD-1/PD-L1 Immunotherapy and Potential Combination Treatment in Non-Small Cell Lung Cancer.
    Li JX, Huang JM, Jiang ZB, Li RZ, et al · · 2019 · cited 45× · PMID 31838881 · DOI 10.1177/1534735419890020
  3. Ongoing clinical trials of PD-1 and PD-L1 inhibitors for lung cancer in China.
    Liu SY, Wu YL. · · 2017 · cited 38× · PMID 28679395 · DOI 10.1186/s13045-017-0506-z
  4. KEYNOTE-033: Randomized phase 3 study of pembrolizumab vs docetaxel in previously treated, PD-L1-positive, advanced NSCLC.
    Ren S, Feng J, Ma S, Chen H, et al · · 2023 · cited 18× · PMID 37141294 · DOI 10.1002/ijc.34532
  5. New PDL1 inhibitors for non-small cell lung cancer: focus on pembrolizumab.
    Bylicki O, Paleiron N, Rousseau-Bussac G, Chouaïd C. · · 2018 · cited 12× · PMID 30038505 · DOI 10.2147/ott.s154606
  6. A meta-analysis on immune checkpoint inhibitor efficacy for advanced non-small cell lung cancer between East Asians versus non-East Asians.
    Peng S, Ying AF, Tai BC, Soo RA. · · 2020 · cited 11× · PMID 32953491 · DOI 10.21037/tlcr-20-246
  7. Effectiveness and safety of pembrolizumab for patients with advanced non-small cell lung cancer in real-world studies and randomized controlled trials: A systematic review and meta-analysis.
    Yang B, Wang B, Chen Y, Wan N, et al · · 2023 · cited 9× · PMID 36824127 · DOI 10.3389/fonc.2023.1044327
  8. KEYNOTE-032: A Randomized Phase I Study of Pembrolizumab in Chinese Patients with Advanced Non-Small Cell Lung Cancer.
    Ma Y, Fang W, Zhang Y, Yang Y, et al · · 2020 · cited 8× · PMID 32134163 · DOI 10.1634/theoncologist.2020-0067

Verify or expand the search:

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Trials by the same sponsor.

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