CA209-057

Bristol-Myers Squibb

Chaussee de la Hulpe 185, Brussels, Belgium, 1170

EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com

Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.com

No

No

No

Final

08 Apr 2022

No

Yes

17 Dec 2021

No

To assess overall survival (OS) after administration of BMS-936558 (nivolumab) versus docetaxel in prior platinum-based doublet chemotherapy treated metastatic non-squamous NSCLC participants.

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.

02 Nov 2012

No

Yes

Argentina: 9

Australia: 16

Austria: 10

Brazil: 24

Canada: 10

Chile: 19

Czechia: 5

France: 49

Germany: 45

Hong Kong: 1

Hungary: 1

Italy: 43

Mexico: 18

Norway: 5

Peru: 6

Poland: 25

Romania: 10

Russian Federation: 14

Singapore: 5

Spain: 49

Switzerland: 13

United States: 205

582

242

0

0

0

0

0

0

339

241

2

Randomization

Randomised - controlled

Yes

Nivolumab

Solution for injection

Intravenous use

Nivolumab at 480mg every 4 weeks

Nivolumab

Solution for injection

Intravenous use

Nivolumab 3 mg/kg solution intravenously every 2 weeks

Docetaxel

Concentrate for solution for infusion

Intravenous use

Docetaxel 75 mg/m^2 solution intravenously every 3 weeks

Nivolumab

Solution for injection

Intravenous use

Nivolumab 3 mg/kg solution intravenously every 2 weeks

Nivolumab

Solution for injection

Intravenous use

Nivolumab at 480mg every 4 weeks

Treatment

Randomised - controlled

Yes

Nivolumab

Solution for injection

Intravenous use

Nivolumab at 480mg every 4 weeks

Nivolumab

Solution for injection

Intravenous use

Nivolumab 3 mg/kg solution intravenously every 2 weeks

Docetaxel

Concentrate for solution for infusion

Intravenous use

Docetaxel 75 mg/m^2 solution intravenously every 3 weeks

Nivolumab

Solution for injection

Intravenous use

Nivolumab 3 mg/kg solution intravenously every 2 weeks

Nivolumab

Solution for injection

Intravenous use

Nivolumab at 480mg every 4 weeks

Nivolumab

Docetaxel

Nivolumab

Docetaxel

Nivolumab

Docetaxel

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.

Primary

Randomization until 413 deaths, up to March 2015 (approximately 29 months)

Nivolumab v Docetaxel

582

Pre-specified

0.73

2-sided

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 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.

Secondary

From randomization to date of objectively documented progression (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.

Secondary

From randomization to the date of first confirmed response (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. Participants who neither progressed nor died were censored on the date of their last evaluable tumor assessment. Median computed using Kaplan-Meier method.

Secondary

From randomization to date of 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 also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. Median computed using the Kaplan-Meier method.

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)

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 representing the best possible score and 100 being the worst possible score. The average symptom burden index score at each assessment was defined as the mean of the 6 symptom-specific questions of the LCSS. 95% CIs were computed using Clopper-Pearson Method.

Secondary

Randomization to Week 12

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. NOTE: The number of participants analyzed for each PD-L1 expression parameter may vary depending on the number of participants who had a tumor biopsy assessed for PD-L1 expression.

Secondary

From randomization to the date of death or last known date alive (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 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.

Secondary

From randomization to date of objectively documented progression (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 08-Apr-2022).

Post-hoc

From randomization to the date of death or last known date alive (up to approximately 110 months)

All-cause mortality assessed from first dose to study completion (up to 110 months). SAEs and NSAEs assessed from first dose to 100 days after last dose (up to 108 months).

24.1

NIVOLUMAB 480 mg

NIVOLUMAB 3 mg/kg

Extension phase of DOCETAXEL arm: NIVOLUMAB 3 mg/kg

Extension phase of DOCETAXEL arm: NIVOLUMAB 480 mg

DOCETAXEL