Efficacy Study of Nivolumab Compared to Docetaxel in Subjects Previously Treated With Advanced or Metastatic Non Small Cell Lung Cancer (CheckMate 078)

An Open-label Randomized Multinational Phase 3 Trial of Nivolumab Versus Docetaxel in Previously Treated Subjects With Advanced or Metastatic Non-small Cell Lung Cancer (CheckMate 078: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 078)

The purpose of this study is to determine whether Nivolumab improves life expectancy compared to Docetaxel in Subjects with Advanced or Metastatic Non-small Cell Lung Cancer who have failed prior platinum-based doublet chemotherapy.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 504
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Local Institution - 0031
  • Beijing, China, 100021
    • Local Institution - 0029
  • Shanghai, China, 200030
    • Local Institution - 0014
  • Shanghai, China, 200030
    • Local Institution - 0028
  • Beijing
    • Beijing, Beijing, China, 100021
      • Local Institution - 0051
    • Beijing, Beijing, China, 100032
      • Local Institution - 0007
    • Beijing, Beijing, China, 100071
      • Local Institution - 0032
    • Beijing, Beijing, China, 100853
      • Local Institution - 0026
  • Chongqing
    • Chongqing, Chongqing, China, 400042
      • Local Institution - 0020
  • Fujian
    • Fuzhou, Fujian, China, 350025
      • Local Institution - 0015
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Local Institution - 0003
    • Guangzhou, Guangdong, China, 510080
      • Local Institution - 0002
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Local Institution - 0024
  • Hunan
    • Changsha, Hunan, China, 410008
      • Local Institution - 0023
    • Changsha, Hunan, China, 410013
      • Local Institution - 0012
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Local Institution - 0034
  • Jilin
    • Changchun, Jilin, China, 130012
      • Local Institution - 0006
    • Changchun, Jilin, China, 130021
      • Local Institution - 0022
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Local Institution - 0017
    • Shanghai, Shanghai, China, 200433
      • Local Institution - 0025
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Local Institution - 0011
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Local Institution - 0009
    • Hangzhou, Zhejiang, China
      • Local Institution - 0008
    • Hangzhou, Zhejiang, China, 310016
      • Local Institution - 0010
• Hong Kong
  • Hong Kong, Hong Kong
    • Local Institution - 0049
• Russian Federation
  • Chelyabinsk, Russian Federation, 454048
    • Local Institution - 0039
  • Moscow, Russian Federation, 105229
    • Local Institution - 0052
  • Moscow, Russian Federation, 121309
    • Local Institution - 0046
  • St. Petersburg, Russian Federation, 194291
    • Local Institution - 0042
  • St. Petersburg, Russian Federation, 198255
    • Local Institution - 0041
  • St.petersburg, Russian Federation, 197758
    • Local Institution - 0040
• Singapore
  • Singapore, Singapore, 119228
    • Local Institution - 0048
  • Singapore, Singapore, 308433
    • Local Institution - 0037

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Disease progression experienced during or after one prior platinum containing doublet chemotherapy
• Stage IIIb/IV or recurrent disease
• Male and Female ≥ 18 years of age
• Measurable disease per RECIST 1.1
• Performance Status ≤ 1

Exclusion Criteria:

• History of Carcinomatous meningitis
• Active Central nervous system (CNS) metastases
• History of auto immune diseases
• Prior treatment with Docetaxel
• Prior treatment with ipilimumab or any drug targeting T-Cell costimulation or checkpoint pathways

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Nivolumab; Nivolumab Intravenous infusion specified dose on specified days	Drug: Nivolumab
Active Comparator: Arm B: Docetaxel; Docetaxel Intravenous infusion specified dose on specified days	Drug: Docetaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Overall Survival	OS was defined as the time between the date of randomization and the date of death. For subjects without documentation of death, OS was censored on the last date the subject was known to be alive	From randomization to the date of death or date participant was last known to be alive (assessed from December 2015 to Oct 2017 approximately 22 months)
Overall Survival Rate	OS was defined as the time between the date of randomization and the date of death. For subjects without documentation of death, OS was censored on the last date the subject was known to be alive. Rates provided are Kaplan-Meier estimates.	From first dose to the date of death or date participant was last known to be alive (assessed from December 2015 to Oct 2017 approximately 22 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Investigator assessed ORR was defined as the number of participants whose best objective response (BOR) was a confirmed complete response (CR) or confirmed partial response (PR), as determined by the investigator, divided by the number of randomized participants. 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.	From date of first dose up to partial or complete response (up to approximately 90 months)
Overall Survival (OS) in Subpopulations	OS was defined as the time between the date of randomization and the date of death. For participants without documentation of death, OS was censored on the last date the participant was known to be alive. Test stratified by histology (SQ vs NSQ), PD-L1 status at 1% expression level (positive vs negative/unevaluable).	From randomization to the date of death or date participant was last known to be alive (up to approximately 90 months)
Progression Free Survival (PFS)	PFS was defined as the time from randomization to the date of the first documented tumor progression as determined by investigators per RECIST 1.1, or death due to any cause. Clinical deterioration in the absence of unequivocal evidence of progression was not considered progression for purposes of determining PFS. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Participants who did not have disease progression or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on study tumor assessments and did not die were censored at the randomization date. Participants who started any subsequent anti-cancer therapy (including on-treatment palliative RT of non-target bone lesions, skin lesions or CNS lesions) without a prior reported progression were censored at the last evaluable tumor assessment prior to or on initiation of the subsequent anti-cancer therapy.	From the time of randomization to the date of the first documented tumor progression or death due to any cause (up to approximately 90 months)
Progression Free Survival Rate	Clinical deterioration in the absence of unequivocal evidence of progression (per RECIST 1.1) is not considered progression for purposes of determining PFS. Participants who die without a reported prior progression will be considered to have progressed on the date of their death. Participants who did not have disease progression or die will be censored on the date of their last evaluable tumor assessment. Participants who did not have any on study tumor assessments and did not die will be censored at the randomization date. Participants who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last evaluable tumor assessment prior to or on initiation of the subsequent anti-cancer therapy. Six month progression-free survival rate as estimated using the Kaplan-Meier method	From the time of randomization up to 6 months
Time to Treatment Failure (TTF)	TTF was defined as the minimum of the time from randomization to disease progression (per RECIST 1.1 or clinical), death or last dose date if a participant discontinued from treatment for any reasons other than "maximum clinical benefit" and "administrative reasons by sponsor". TTF was considered as event at the randomization date for participants who were randomized but not treated. TTF was censored at the last dose date for participants who discontinued treatment due to "maximum clinical benefit" or "administrative reasons by sponsor". TTF was censored at the last dose date for participants who continued on treatment without progression or death. This outcome measure was prespecified in the protocol to only be evaluated through the first Interim Analysis, which occurred in June 2017.	From randomization up to disease progression, death, or last dose (up to approximately 17 months)
Number of Participants Experiencing Treatment-Related Adverse Events (AEs)	A treatment-related Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and is determined to be associated with the study treatment. Adverse events are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.	From first dose up to 100 days after last dose (up to 93 months)
Number of Participants Experiencing Treatment-Related Serious Adverse Events (SAEs)	A treatment-related Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization and is determined to be associated with the study treatment.	From first dose up to 100 days after last dose (up to 93 months)
Disease Related Symptom Deterioration Rate by Week 12 and Week 24	Disease-Related Symptom Deterioration Rate is the percentage of participants with >=10 points increase from baseline in Average Symptom Burden Index (ASBI) score at any time between randomization and the timepoints. The Lung Cancer Symptom Scale (LCSS) measures 6 items (loss of appetite, fatigue, coughing, shortness of breath, hemoptysis, pain) and 3 symptom burden items (disease-related functional limitations, quality of life) with responses captured using a 100mm visual analog scale (VAS). Scores range from 0 (highest quality of life) to 100 (worst quality of life) and is derived by dividing the length of the line drawn from the lowest possible response to the patient's response by the length of the VAS and multiplying the result by 100. An ASBI score can be derived as the mean of scores for the 6 symptom-related items with a clinically meaningful change in ASBI score being 10 points and a meaningful deterioration in symptoms is a mean post-baseline score change >= 10 points.	At Week 12 and Week 24

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

General Publications

• Wu YL, Lu S, Cheng Y, Zhou C, Wang J, Mok T, Zhang L, Tu HY, Wu L, Feng J, Zhang Y, Luft AV, Zhou J, Ma Z, Lu Y, Hu C, Shi Y, Baudelet C, Cai J, Chang J. Nivolumab Versus Docetaxel in a Predominantly Chinese Patient Population With Previously Treated Advanced NSCLC: CheckMate 078 Randomized Phase III Clinical Trial. J Thorac Oncol. 2019 May;14(5):867-875. doi: 10.1016/j.jtho.2019.01.006. Epub 2019 Jan 17.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2015
• Primary Completion (Actual): September 15, 2017
• Study Completion (Actual): November 24, 2023

Study Registration Dates

• First Submitted: November 22, 2015
• First Submitted That Met QC Criteria: November 22, 2015
• First Posted (Estimated): November 24, 2015

Study Record Updates

• Last Update Posted (Actual): November 19, 2024
• Last Update Submitted That Met QC Criteria: November 15, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Nivolumab
• Other Study ID Numbers: CA209-078; 2015-001893-16 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No