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Carcinoma

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Carcinoma, Bronchogenic

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Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Ramucirumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Tubulin Modulators

Antimitotic Agents

Angiogenesis Inhibitors

Growth Inhibitors

Immunologic Factors

10 milligrams per kilogram (mg/kg) administered intravenously (IV) on Day 1 of 21-day cycle until disease progression, unacceptable toxicity, or another withdrawal criterion is met

Administered IV on Day 1 of 21-day cycle until disease progression, unacceptable toxicity, or another withdrawal criterion is met

Placebo (for Ramucirumab)

75 milligrams per square meter (mg/m\^2) (60 mg/m\^2 for the countries of Korea and Taiwan only with protocol amendment dated 22 May 2012) administered IV on Day 1 of 21-day cycle until disease progression, unacceptable toxicity, or another withdrawal criterion is met

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9AM - 5PM Eastern time (UTC/GMT - 5 hours, EST)

The purpose of the study is to compare the survival of participants who receive chemotherapy and ramucirumab versus chemotherapy alone as second line treatment for NSCLC after prior first line platinum-based chemotherapy.

A Study of Chemotherapy and Ramucirumab Versus Chemotherapy Alone in Second Line Non-Small Cell Lung Cancer (NSCLC) Participants Who Received Prior First Line Platinum-based Chemotherapy

A Randomized, Double-Blind, Phase 3 Study of Docetaxel and Ramucirumab Versus Docetaxel and Placebo in the Treatment of Stage IV Non-Small Cell Lung Cancer Following Disease Progression After One Prior Platinum-Based Therapy

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Data presented are the number of participants who experienced at least 1 TEAE, Grade 3, 4, or 5 TEAE, treatment-emergent serious adverse event (SAE), TEAE leading to discontinuation of study treatment (ramucirumab/placebo or docetaxel), and TEAE leading to death. Clinically significant events were defined as treatment-emergent SAEs and other non-serious adverse events (AEs) regardless of causality. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

Overall survival was the time from randomization until the date of death from any cause. Participants who were alive at the end of the follow-up period (or lost to follow-up) were censored on the last date the participant was known to be alive.

PFS time was the time from randomization until the date of objectively determined progressive disease (PD) or death due to any cause, whichever occurred first. According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), PD was at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the 20% relative increase, the sum must have also demonstrated an absolute increase of at least 5 millimeters (mm). The appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions was also considered progression. Participants without objectively determined PD who were alive at the end of the follow-up period (or lost to follow-up) were censored on the date of the participant's last complete radiographic tumor assessment; if no baseline or post-baseline radiologic assessment was available, the participant was censored at the date of randomization.

Participants achieved an objective response if they had a best overall response of partial response (PR) or complete response (CR). According to RECIST v1.1, PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter; CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to \<10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels \[if tumor markers were initially above the upper limit of normal (ULN)\]. The percentage of participants who achieved an objective response=(number of participants with CR or PR)/(number of participants assessed)\*100.

Participants achieved disease control if they had a best overall response of PR, CR or stable disease (SD). According to RECIST v1.1, PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter; CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to \<10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels (if tumor markers were initially above the ULN). SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started. The percentage of participants who achieved disease control=(number of participants with CR, PR, or SD)/(number of participants assessed)\*100.

The LCSS consisted of 9 items: 6 items focused on lung cancer symptoms \[loss of appetite, fatigue, cough, dyspnea (shortness of breath), hemoptysis (blood in sputum), and pain\] and 3 items were global items (symptom distress, interference with activity level, and global quality of life). Participant responses to each item were measured using visual analogue scales (VAS) with 100-mm lines. A higher score for any item represented a higher level of symptoms/problems. The Average Symptom Burden Index (ASBI) was the mean of the 6 symptom items of the LCSS, and the Total LCSS was the mean of all 9 LCSS items. ASBI and Total LCSS were not computed for a participant if he/she had 1 or more missing values for the 6 and 9 items, respectively. Maximum improvement in LCSS scores, ASBI, and Total LCSS score was the largest decrease from baseline for each variable, which was the smallest (most negative or smallest positive) non-missing value among all change from baseline values for each variable.

The EQ-5D is a quality-of-life instrument that consists of 2 parts. The first part (Health State Index score) allowed participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a scale from 1 to 3 (no problem, some problems, and extreme problems, respectively). These combinations of attributes were converted into a weighted Health State Index score according to a United Kingdom population-based algorithm; the possible values for the Health State Index score ranged from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension). The second part of the EQ-5D was a VAS that allowed participants to rate their present health condition. Possible EQ-5D VAS scores ranged from 0 (worst imaginable health state) to 100 (best imaginable health state).

The number of participants who had treatment-emergent or follow-up emergent anti-drug antibodies (ADA) is reported. Participants with treatment-emergent ADA were defined as participants who had any sample from baseline through Cycle 5 pre-infusion that was a 4-fold increase (2 dilution increase) in immunogenicity titer over the baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20). Participants with follow-up emergent ADA were defined as participants who had any sample during 30 days post last infusion that was a 4-fold increase (2 dilution increase) in immunogenicity titer over the baseline titer.

Eli Lilly and Company

Safety Population: All randomized participants who received any quantity of study treatment, grouped by the treatment they actually received.

Three participants randomized to placebo and docetaxel received 1 dose of ramucirumab in error.

On Day 1 of each 21-day cycle, participants received ramucirumab DP followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

* Ramucirumab DP: 10 mg/kg administered intravenously.
* Docetaxel: 75 mg/m\^2 (60 mg/m\^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.

Ramucirumab and Docetaxel

On Day 1 of each 21-day cycle, participants received placebo followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

* Placebo (matching Ramucirumab DP): 10 mg/kg administered intravenously.
* Docetaxel: 75 mg/m\^2 (60 mg/m\^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.

Placebo and Docetaxel

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Taiwan

Greece

Spain

Israel

Russian Federation

Italy

Switzerland

India

France

Puerto Rico

Netherlands

Korea, Republic of

Turkey

Austria

United Kingdom

Hungary

Mexico

Canada

Argentina

Brazil

Poland

Romania

Norway

Germany

New Zealand

Sweden

Region of Enrollment

Intent-to-Treat (ITT) population: All randomized participants grouped according to their assigned treatment at randomization.

Three participants randomized to placebo and docetaxel received 1 dose of ramucirumab in error. They are included in the placebo and docetaxel arm in the ITT population and are included in the ramucirumab and docetaxel arm in the Safety population.

Chief Medical Officer

Intent-to-Treat (ITT) population: All randomized participants grouped according to their assigned treatment at randomization. Participants censored: ramucirumab and docetaxel arm = 200 participants; placebo and docetaxel arm = 169 participants.

Overall Survival

ITT population: All randomized participants grouped according to their assigned treatment at randomization. Participants censored: ramucirumab and docetaxel arm = 70 participants; placebo and docetaxel arm = 42 participants.

Progression-Free Survival (PFS) Time

ITT population: All randomized participants grouped according to their assigned treatment at randomization.

Percentage of Participants Achieving an Objective Response (Objective Response Rate)

Percentage of Participants Achieving Disease Control (Disease Control Rate)

Loss of Appetite (n=473, 471)

Fatigue (n=473, 472)

Cough (n=476, 473)

Dyspnea (n=472, 477)

Hemoptysis (n=475, 475)

Pain (n=476, 475)

Symptom Distress (n=474, 472)

Interference With Activity Level (n=474, 472)

Global Quality of Life (n=467, 469)

ASBI (n=455, 456)

Total LCSS (n=446, 446)

Randomized participants grouped according to their assigned treatment at randomization, who had a baseline and at least 1 post-baseline LCSS score.

Maximum Improvement on Lung Cancer Symptom Scale (LCSS)

Health State Index Score (n=266, 272)

Health State VAS Score (n=272, 254)

Randomized participants grouped according to their assigned treatment at randomization, who had an EQ-5D assessment at a baseline and 30 days post treatment.

Change From Baseline to 30-Day Follow-Up Visit on European Quality of Life Questionnaire-5 Dimension (EQ-5D) Health State Scores

Cmax at Cycle 3

Cmin at Cycle 3

Cmax at Cycle 5

Cmin at Cycle 5

Participants assigned to the ramucirumab and docetaxel arm at randomization, who had evaluable ramucirumab pharmacokinetic (PK) data to calculate Cmax and Cmin.

Maximum and Minimum Serum Concentrations (Cmax and Cmin) of Ramucirumab

Treatment-Emergent ADA (n=599, 598)

Follow-Up Emergent ADA (n=506, 481)

Randomized participants who received any quantity of study treatment, grouped by the treatment they actually received, who had a baseline and at least 1 post-baseline ADA assessment.

Number of Participants With Anti-Ramucirumab Antibodies

At least 1 TEAE

At least 1 Grade 3, 4, or 5 TEAE

At least 1 treatment-emergent SAE

TEAE leading to study drug discontinuation

TEAE leading to death

Deaths While On Treatment

Deaths During 30 Days Post Last Dose

Safety population: Randomized participants who received any quantity of study drug, grouped by the treatment they actually received.

Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs) or Died

On Day 1 of each 21-day cycle, participants received ramucirumab drug product (DP) followed by docetaxel. Treatment continued until disease progression, unacceptable toxicity, or other withdrawal criteria were met.

* Ramucirumab DP: 10 milligrams per kilogram (mg/kg) administered intravenously.
* Docetaxel: 75 milligrams per square meter (mg/m\^2) (60 mg/m\^2 for the countries of Korea and Taiwan only, with protocol amendment dated 22 May 2012) administered intravenously.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of Chemotherapy and Ramucirumab Versus Chemotherapy Alone in Second Line Non-Small Cell Lung Cancer (NSCLC) Participants Who Received Prior First Line Platinum-based Chemotherapy	NCT01168973	Non-Small Cell ...	Ramucirumab Placebo (for Ra... Docetaxel	18 Years -	Eli Lilly and Company
A Study of Chemotherapy and Ramucirumab Versus Chemotherapy Alone in Second Line Non-Small Cell Lung Cancer (NSCLC) Participants Who Received Prior First Line Platinum-based Chemotherapy	NCT01168973	Non-Small Cell ...	Ramucirumab Placebo (for Ra... Docetaxel	18 Years -	Eli Lilly and Company

Spots Global Cancer Trial Database for placebo (for ramucirumab)