A Safety and Efficacy Study of Farletuzumab in Participants With Adenocarcinoma of the Lung

PFS was defined as the time from the date of randomization to the date of the first observation of investigator-assessed (radiology review) progression based on Response Evaluation Criteria In Solid Tumors (RECIST) v.1.1 or other protocol-approved measures of disease progression (e.g., new occurrence of positive fluid cytology, newly diagnosed evidence of disease progression from histologic samples, PET-positive metastases, or new bone or brain metastases), or date of death, whatever the cause. Disease progression as assessed by the investigator per RECIST v1.0 was defined as at least a 20% increase in sum of longest diameters (RECIST definition) compared to baseline (or lowest sum while on study if less than baseline), or any new lesions (measurable or nonmeasurable).

Time frame: From date of first administration of study drug up to 6 month follow-up from randomization of the last participant, i.e., cut-off date 15 Dec 2012 for primary analysis and cut-off date of 1 Nov 2013 or up to approximately 28 months for final analysis

Population: The ITT population included all randomized participants who received at least 1 dose of test article (placebo or farletuzumab), with treatment assignments designated according to actual study treatment received. This was the primary analysis population for evaluating treatment administration, tolerability, and safety.

DR was derived for those participants with objective evidence of CR or PR. DR was defined as the time (in months) from first documentation of objective response (CR or PR) to the first documentation of disease progression (ie, objective tumor progression as assessed by investigator's radiology review or other protocol-approved measures of disease progression) or death due to any cause. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Time frame: From the first documentation of objective response (CR or PR) to the first documentation of disease progression, death due to any cause, or cut-off date of 1 Nov 2013, i.e., up to approximately 28 months for final analysis

Population: Tumor Response (TR) Evaluable Analysis Set (responders only) included all participants who received at least 1 dose of test article and who had a baseline assessment and at least 1 on-treatment assessment performed, sufficient to assess the endpoint of interest. The TR Evaluable Analysis Set was used for all RECIST assessments of tumor response.

An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered with an investigational product. A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose; resulted in death, was life-threatening (i.e., the participant was at a risk of death at the time of the event; this did not include an event that hypothetically might have caused death if it had been more severe), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, or was a congenital abnormality/birth defect. In this study, TEAEs (defined as an AE that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) were assessed.

Time frame: For each participant, from the first dose till 30 days after the last dose or cut-off date of 1 Nov 2013, i.e., up to approximately 28 months for final analysis

Population: The safety analysis set (SAS) included randomized participants who received at least 1 dose of test article, with treatment assignments designated according to actual study treatment received. This was the primary analysis population for evaluating treatment administration, tolerability, and safety.

ORR, defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) as determined by investigator's radiologic assessments using RECIST 1.1 for target lesions and assessed by Magnetic resonance imaging (MRI) and computerized tomography (CT) scan (for double blind treatment period i.e. Randomization Phase). CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR = CR + PR.

Time frame: From Day 1 until documented radiographic progression, other protocol-approved measures of disease progression, withdrawal by participant, death due to any cause, or cut-off date of 1 Nov 2013, i.e., up to approximately 28 months for final analysis

Population: The ITT population included all randomized participants who received at least 1 dose of test article (placebo or farletuzumab), with treatment assignments designated according to actual study treatment received. This was the primary analysis population for evaluating treatment administration, tolerability, and safety.

OS was defined as the time (in months) from the date of randomization to the date of death, regardless of cause.

Time frame: From the date of randomization to the date of death due to any cause or up to cut-off date of 1 Nov 2013 (up to approximately 28 months) for final analysis

Population: The ITT population included all randomized participants who received at least 1 dose of test article (placebo or farletuzumab), with treatment assignments designated according to actual study treatment received. This was the primary analysis population for evaluating treatment administration, tolerability, and safety.