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NCT02041533

An Open-Label, Randomized, Phase 3 Trial of Nivolumab Versus Investigator's Choice Chemotherapy as First-Line Therapy for Stage IV or Recurrent PD-L1+ Non-Small Cell Lung Cancer (CheckMate 026)

Completed Phase 3 Results posted Last updated 2 March 2023
What this trial tests

Phase 3 trial testing Nivolumab in Stage IV or Recurrent Non-Small Cell Lung Cancer in 541 participants. Completed in 27 May 2022.

Timeline
27 March 2014
Primary endpoint
1 July 2016
27 May 2022

Quick facts

Lead sponsorBristol-Myers Squibb
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment541
Start date27 March 2014
Primary completion1 July 2016
Estimated completion27 May 2022
Sites141 locations across Italy, Finland, Japan, Taiwan, Poland, South Korea, Netherlands, Belgium

Drugs / interventions tested

Conditions studied

Sponsor

Bristol-Myers Squibb — full company profile →

Who can join

18 and older, any sex, with Stage IV or Recurrent Non-Small Cell Lung Cancer. 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 in Participants With PD-L1 Expression >= 5% Primary · From date of randomization until date of documented tumor progression (assessed up to August 2016, approximately 28 months)

Progression-Free Survival (PFS) was defined as the time between the date of randomization and the first date of documented tumor progression, as determined by the Independent Radiology Review Committee (IRRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause, whichever occurs first. Participants who die without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor ass

GroupValue95% CI
Nivolumab4.212.96 – 5.55
Investigator Choice of Chemotherapy5.885.42 – 6.93
Progression-Free Survival in All Randomized Participants Secondary · From date of randomization until date of documented tumor progression (assessed up to August 2016, approximately 28 months)

Progression-Free Survival (PFS) was defined as the time between the date of randomization and the first date of documented tumor progression, as determined by the Independent Radiology Review Committee (IRRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause, whichever occurs first. Participants who die without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor ass

GroupValue95% CI
Nivolumab4.213.06 – 5.52
Investigator Choice of Chemotherapy5.825.42 – 6.90
Overall Survival in Participants With PD-L1 Expression >= 5% Secondary · From date of randomization to date of death (up to approximately 89 months)

Overall Survival (OS) was defined as the time from randomization to the date of death. A participant who had not died was censored at the last known alive date. OS was censored at the date of randomization for participants who were randomized but had no follow-up.

GroupValue95% CI
Nivolumab14.3611.66 – 17.08
Investigator Choice of Chemotherapy13.2110.81 – 17.28
Overall Survival in All Randomized Participants Secondary · From date of randomization to date of death (up to approximately 89 months)

Overall Survival (OS) was defined as the time from randomization to the date of death. A participant who had not died was censored at the last known alive date. OS was censored at the date of randomization for participants who were randomized but had no follow-up.

GroupValue95% CI
Nivolumab13.7311.76 – 15.41
Investigator Choice of Chemotherapy13.8011.01 – 16.99
Objective Response Rate (ORR) in Participants With PD-L1 Expression >= 5% Secondary · From date of randomization until date of documented tumor progression or subsequent anti-cancer therapy, whichever occurs first (assessed up to August 2016, approximately 28 months)

ORR was defined as the proportion of randomized participants who achieved a Best Overall Response (BOR) of CR or PR using the RECIST v1.1 criteria per Independent Radiology Review Committee (IRRC) assessment. BOR was defined as the best response designation recorded between the date of randomization and the date of objectively documented progression or start of subsequent anti-cancer therapy, whichever occurred first. For participants without documented progression or subsequent therapy, all available response designations contributed to the BOR assessment. For participants who continued treat

GroupValue95% CI
Nivolumab26.120.3 – 32.5
Investigator Choice of Chemotherapy33.527.2 – 40.3
Disease-related Symptom Improvement Rate by Week 12 Secondary · From date of randomization to week 12

The Lung Cancer Symptom Score (LCSS) is a validated instrument designed to assess the impact of treatment on disease-related symptoms. It consists of 6 symptom-specific questions related to dyspnea, cough, fatigue, pain, hemoptysis and anorexia plus 3 summary items: symptom distress, interference with activity, and global HRQoL. The degree of impairment was recorded on a 100 mm visual analogue scale with scores from 0 to 100 with zero representing the best score. Disease-related symptom improvement rate by Week 12 is defined as the proportion of all randomized (all PD-L1+) participants who had

GroupValue95% CI
Nivolumab35.429.7 – 41.4
Investigator Choice of Chemotherapy33.728.1 – 39.7

Adverse events — posted to ClinicalTrials.gov

Time frame: Participants were assessed for All-Cause Mortality from the date of their randomization until study completion (up to approximately 89 months). SAEs and Other AEs were assessed from their first dose to 100 days following their last dose (up to approximately 89 months).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Nivolumab
Serious: 195/267 (73%)
Deaths: 233/271
Investigator Choice of Chemotherapy
Serious: 203/263 (77%)
Deaths: 92/270
Post Chemotherapy Optional Nivolumab
Serious: 110/159 (69%)
Deaths: 136/159

Serious adverse events (265 terms)

ReactionSystemNivolumabInvestigator Choice of Che…Post Chemotherapy Optional…
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
PneumoniaInfections and infestations
AnaemiaBlood and lymphatic system disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
FatigueGeneral disorders
Cancer painNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous systemNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Pleural effusionRespiratory, thoracic and mediastinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
Myocardial infarctionCardiac disorders
DiarrhoeaGastrointestinal disorders
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
General physical health deteriorationGeneral disorders
Aspartate aminotransferase increasedInvestigations
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
SepsisInfections and infestations
Alanine aminotransferase increasedInvestigations
DehydrationMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
Other adverse events (81 terms — click to expand)

ReactionSystemNivolumabInvestigator Choice of Che…Post Chemotherapy Optional…
NauseaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
FatigueGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
VomitingGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Oedema peripheralGeneral disorders
Back painMusculoskeletal and connective tissue disorders
PyrexiaGeneral disorders
NeutropeniaBlood and lymphatic system disorders
ArthralgiaMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
HypomagnesaemiaMetabolism and nutrition disorders
Neutrophil count decreasedInvestigations
Weight decreasedInvestigations
AstheniaGeneral disorders
DizzinessNervous system disorders
ThrombocytopeniaBlood and lymphatic system disorders
InsomniaPsychiatric disorders
Aspartate aminotransferase increasedInvestigations
PruritusSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
Platelet count decreasedInvestigations
HyponatraemiaMetabolism and nutrition disorders
Abdominal painGastrointestinal disorders
Blood creatinine increasedInvestigations
White blood cell count decreasedInvestigations
Alanine aminotransferase increasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Productive coughRespiratory, thoracic and mediastinal disorders
HypoalbuminaemiaMetabolism and nutrition disorders
MyalgiaMusculoskeletal and connective tissue disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
AlopeciaSkin and subcutaneous tissue disorders
Dry skinSkin and subcutaneous tissue disorders
Chest painGeneral disorders

Most-reported serious reactions: Malignant neoplasm progression, Pneumonia, Anaemia, Pulmonary embolism, Pyrexia, Dyspnoea, Pneumonitis, Fatigue.

Data from ClinicalTrials.gov NCT02041533 adverse events section.

Sponsor's own description

The purpose of this study is to show that Nivolumab will improve progression free survival in subjects with strongly Stage IV or Recurrent PD-L1+ non-small cell lung cancer when compared to chemotherapy

Publications & conference data

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

  1. First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer.
    Carbone DP, Reck M, Paz-Ares L, Creelan B, et al · · 2017 · cited 1995× · PMID 28636851 · DOI 10.1056/nejmoa1613493
  2. 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
  3. The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker.
    Jardim DL, Goodman A, de Melo Gagliato D, Kurzrock R. · · 2021 · cited 935× · PMID 33125859 · DOI 10.1016/j.ccell.2020.10.001
  4. PD-1/PD-L1 inhibitors.
    Sunshine J, Taube JM. · · 2015 · cited 437× · PMID 26047524 · DOI 10.1016/j.coph.2015.05.011
  5. Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer.
    Gettinger S, Rizvi NA, Chow LQ, Borghaei H, et al · · 2016 · cited 412× · PMID 27354485 · DOI 10.1200/jco.2016.66.9929
  6. Systemic Therapy for Stage IV Non-Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update.
    Masters GA, Temin S, Azzoli CG, Giaccone G, et al · · 2015 · cited 344× · PMID 26324367 · DOI 10.1200/jco.2015.62.1342
  7. Development of PD-1/PD-L1 Pathway in Tumor Immune Microenvironment and Treatment for Non-Small Cell Lung Cancer.
    He J, Hu Y, Hu M, Li B. · · 2015 · cited 290× · PMID 26279307 · DOI 10.1038/srep13110
  8. Antagonists of PD-1 and PD-L1 in Cancer Treatment.
    Lipson EJ, Forde PM, Hammers HJ, Emens LA, et al · · 2015 · cited 236× · PMID 26320063 · DOI 10.1053/j.seminoncol.2015.05.013

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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/NCT02041533.

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