NCT01673867: CheckMate057

Study of BMS-936558 (Nivolumab) Compared to Docetaxel in Previously Treated Metastatic Non-squamous NSCLC

Completed Phase 3 Results posted Last updated 8 February 2023

What this trial tests

Phase 3 trial testing Nivolumab in Non-Squamous Cell Non-small Cell Lung Cancer in 582 participants. Completed in 17 December 2021.

Timeline

2 November 2012

Primary endpoint
5 February 2015

17 December 2021

Quick facts

Lead sponsor	Bristol-Myers Squibb
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	582
Start date	2 November 2012
Primary completion	5 February 2015
Estimated completion	17 December 2021
Sites	119 locations across Hong Kong, Italy, Poland, Russia, Mexico, United States, France, Austria

Drugs / interventions tested

• Nivolumab (nivolumab) — full drug profile →
• Docetaxel (Docetaxel) — full drug profile →

Conditions studied

• Non-Squamous Cell Non-small Cell Lung Cancer — all drugs for Non-Squamous Cell Non-small Cell Lung Cancer →

Sponsor

Bristol-Myers Squibb — full company profile →

Who can join

18 and older, any sex, with Non-Squamous Cell 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.

Overall Survival (OS) Time in Months for All Randomized Participants at Primary Endpoint Primary · Randomization until 413 deaths, up to March 2015 (approximately 29 months)

Overall survival was defined as the time from randomization to the date of death. A participant who has not died will be censored at last known date alive. OS will be followed continuously while participants are on the study drug and every 3 months via in-person or phone contact after participants discontinue the study drug. Median and hazard ratio computed using Kaplan-Meier method.

Group	Value	95% CI
Nivolumab	12.19	9.66 – 14.98
Docetaxel	9.36	8.05 – 10.68

Objective Response Rate (ORR) Secondary · From randomization to date of objectively documented progression (up to approximately 110 months)

ORR was defined as the percentage of participants whose Best Overall Response (BOR) was a confirmed Complete Response (CR) or Partial Response (PR). BOR was defined as the best investigator-assessed response designation, recorded between the date of randomization and the date of objectively documented progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or the date of subsequent anti-cancer therapy (excluding on-treatment palliative radiotherapy of non-target bone lesions or Central Nervous System (CNS) lesions), whichever occurred first. CR = Disappearance of

Group	Value	95% CI
Nivolumab	19.5	15.1 – 24.5
Docetaxel	12.8	9.1 – 17.2

Time To Objective Response (TTOR) Secondary · From randomization to the date of first confirmed response (up to approximately 110 months)

Time to Objective Response for participants demonstrating a response (either CR or PR) was defined as the time from the date of randomization to the date of the first confirmed response. CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.; PR = At least a 30% decrease in the sum of diameters of target lesions, taking, as reference, the baseline sum diameters.

Group	Value	95% CI
Nivolumab	2.10	1.2 – 34.6
Docetaxel	2.73	1.4 – 31.2

Duration of Objective Response (DOOR) Secondary · From randomization to date of first documented tumor progression or death due to any cause, whichever occurred first (up to approximately 110 months)

DOR was defined as the time from the date of first confirmed response to the date of the first documented tumor progression (per RECIST v1.1), as determined by the investigator, or death due to any cause, whichever occurred first. DOR was evaluated only for confirmed responders (i.e. participants with confirmed CR or PR). CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.; PR = At least a 30% decrease in the sum of diameters of target lesions, taking, as reference, the baseline sum diameters. Part

Group	Value	95% CI
Nivolumab	17.15	10.78 – 30.75
Docetaxel	5.55	4.40 – 7.03

Progression-Free Survival (PFS) Secondary · From randomization to first confirmed response to the date of the first documented tumor progression or death due to any cause, whichever occurred first (up to approximately 110 months)

PFS was defined as the time from randomization to the date of the first documented tumor progression (per RECIST 1.1) or death due to any cause. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Progression will be assessed every 6 weeks (from the first on-study radiographic assessment) until disease progression is noted. Progressive disease was defined as least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must

Group	Value	95% CI
Nivolumab	2.33	2.17 – 3.32
Docetaxel	4.44	3.45 – 4.86

Percentage of Participants Experiencing Disease-Related Symptom Improvement by Week 12 Secondary · Randomization to Week 12

Disease-related symptom improvement rate by Week 12 was defined as the percentage of randomized participants who had a 10 point or greater decrease from baseline in average symptom burden index score at any time between randomization and Week 12. The participant portion of the Lung Cancer Symptom Scale (LCSS) consisted of 6 symptom-specific questions that addressed cough, dyspnea, fatigue, pain, hemoptysis, and anorexia, plus 3 summary items on symptom distress, interference with activity level, and global health-related Quality of Life (QoL). The scores range from 0 to 100, with 0 representin

Group	Value	95% CI
Nivolumab	17.8	13.6 – 22.7
Docetaxel	19.7	15.2 – 24.7

Overall Survival (OS) by PD-L1 Expression at Baseline Secondary · From randomization to the date of death or last known date alive (up to approximately 110 months)

Overall survival was defined as the time from randomization to the date of death. A participant who has not died will be censored at last known date alive. Overall Survival time was measured in months for all randomized participants grouped by their baseline PD-L1 expression level. PD-L1 expression in participants was defined as the percent of disease tumor cells demonstrating plasma membrane PD-L1 staining of any intensity using an immunohistochemistry (IHC) assay. Median computed using the Kaplan-Meier method.

Participants with baseline PD-L1 expression ≥ 5%

Group	Value	95% CI
Nivolumab	19.91	15.08 – 26.12
Docetaxel	8.11	6.47 – 10.05

Participants with baseline PD-L1 expression < 5%

Group	Value	95% CI
Nivolumab	9.86	6.93 – 12.81
Docetaxel	10.28	8.54 – 11.96

Objective Response Rate (ORR) by PD-L1 Expression at Baseline Secondary · From randomization to date of objectively documented progression (up to approximately 110 months)

ORR was defined as the percentage of all randomized participants whose Best Overall Response (BOR) was a confirmed Complete Response (CR) or Partial Response (PR). CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.; PR = At least a 30% decrease in the sum of diameters of target lesions, taking, as reference, the baseline sum diameters. CR+PR, confidence interval based on the Clopper and Pearson method. ORR was reported for all randomized participants grouped by their baseline PD-L1 expression leve

Participants with baseline PD-L1 expression ≥ 5%

Group	Value	95% CI
Nivolumab	36.2	26.5 – 46.7
Docetaxel	12.8	6.6 – 21.7

Participants with baseline PD-L1 expression < 5%

Group	Value	95% CI
Nivolumab	10.9	6.3 – 17.4
Docetaxel	14.5	9.1 – 21.5

Overall Survival (OS) - Extended Collection Secondary · From randomization to the date of death or last known date alive (up to approximately 110 months)

Overall survival was defined as the time from randomization to the date of death. A participant who has not died will be censored at last known date alive. OS will be followed continuously while participants are on the study drug and every 3 months via in-person or phone contact after participants discontinue the study drug. Median computed using Kaplan-Meier method. Note: This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until December 17, 2021).

Group	Value	95% CI
Nivolumab	12.21	9.66 – 15.08
Docetaxel	9.49	8.11 – 10.74

Adverse events — posted to ClinicalTrials.gov

Time frame: Participants were assessed for all-cause mortality from randomization until study completion (up to approximately 110 months). SAEs and Other AEs were assessed from first dose to 100 days after last dose of study therapy (up to approximately 108 months).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Nivolumab 3 mg/kg

Serious: 172/287 (60%)

Deaths: 258/292

Nivolumab 480 mg

Serious: 5/15 (33%)

Deaths: 2/15

Docetaxel

Serious: 161/268 (60%)

Deaths: 266/290

Extension Phase of Docetaxel Arm: Nivolumab 3 mg/kg

Serious: 9/17 (53%)

Deaths: 14/17

Extension Phase of Docetaxel Arm: Nivolumab 480 mg

Serious: 1/1 (100%)

Deaths: 0/1

Serious adverse events (201 terms)

Reaction	System	Nivolumab 3 mg/kg	Nivolumab 480 mg	Docetaxel	Extension Phase of Docetax…	Extension Phase of Docetax…
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Non-small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—
General physical health deterioration	General disorders	—	—	—	—	—
Pain	General disorders	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Pericardial effusion	Cardiac disorders	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—
Disease progression	General disorders	—	—	—	—	—

Other adverse events (122 terms — click to expand)

Reaction	System	Nivolumab 3 mg/kg	Nivolumab 480 mg	Docetaxel	Extension Phase of Docetax…	Extension Phase of Docetax…
Fatigue	General disorders	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—	—	—
Weight decreased	Investigations	—	—	—	—	—
Neuropathy peripheral	Nervous system disorders	—	—	—	—	—
Paraesthesia	Nervous system disorders	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—	—	—	—
Lacrimation increased	Eye disorders	—	—	—	—	—
White blood cell count decreased	Investigations	—	—	—	—	—
Hypothyroidism	Endocrine disorders	—	—	—	—	—
Pain	General disorders	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—
Dysgeusia	Nervous system disorders	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—
Mucosal inflammation	General disorders	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Non-cardiac chest pain	General disorders	—	—	—	—	—

Most-reported serious reactions: Malignant neoplasm progression, Febrile neutropenia, Pneumonia, Pulmonary embolism, Non-small cell lung cancer, Dyspnoea, Pleural effusion, Respiratory failure.

Data from ClinicalTrials.gov NCT01673867 adverse events section.

Sponsor's own description

The purpose of the study is to compare the overall survival of BMS-936558 (Nivolumab) as compared with Docetaxel in subjects with non-squamous cell non-small cell lung cancer (NSCLC) after failure of prior platinum-based chemotherapy

Publications & conference data

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

1. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer.
   Borghaei H, Paz-Ares L, Horn L, Spigel DR, et al · · 2015 · cited 7479× · PMID 26412456 · DOI 10.1056/nejmoa1507643
2. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab.
   Topalian SL, Sznol M, McDermott DF, Kluger HM, et al · · 2014 · cited 1751× · PMID 24590637 · DOI 10.1200/jco.2013.53.0105
3. 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
4. <i>STK11/LKB1</i> Mutations and PD-1 Inhibitor Resistance in <i>KRAS</i>-Mutant Lung Adenocarcinoma.
   Skoulidis F, Goldberg ME, Greenawalt DM, Hellmann MD, et al · · 2018 · cited 1324× · PMID 29773717 · DOI 10.1158/2159-8290.cd-18-0099
5. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade.
   Morad G, Helmink BA, Sharma P, Wargo JA. · · 2021 · cited 1197× · PMID 34624224 · DOI 10.1016/j.cell.2021.09.020
6. Lung cancer immunotherapy: progress, pitfalls, and promises.
   Lahiri A, Maji A, Potdar PD, Singh N, et al · · 2023 · cited 737× · PMID 36810079 · DOI 10.1186/s12943-023-01740-y
7. Nivolumab Versus Docetaxel in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer: Two-Year Outcomes From Two Randomized, Open-Label, Phase III Trials (CheckMate 017 and CheckMate 057).
   Horn L, Spigel DR, Vokes EE, Holgado E, et al · · 2017 · cited 687× · PMID 29023213 · DOI 10.1200/jco.2017.74.3062
8. New horizons in tumor microenvironment biology: challenges and opportunities.
   Chen F, Zhuang X, Lin L, Yu P, et al · · 2015 · cited 521× · PMID 25857315 · DOI 10.1186/s12916-015-0278-7