Efficacy and Safety Study of ABP 215 Compared With Bevacizumab in Patients With Advanced Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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The purpose of this research study is to compare the effectiveness and safety of ABP 215 against bevacizumab in men and women with advanced non-small cell lung cancer.

Official Title
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A Randomized, Double-blind, Phase 3 Study Evaluating the Efficacy and Safety of ABP 215 Compared With Bevacizumab in Subjects With Advanced Non-Small Cell Lung Cancer

Conditions
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Non-small Cell Lung Cancer Metastatic

Intervention / Treatment
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* Drug: Carboplatin
* Drug: Paclitaxel
* Drug: ABP 215
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed non-squamous non-small cell lung cancer (NSCLC) Subjects must be initiating first-line carboplatin/paclitaxel chemotherapy within 8 days after randomization and expected to receive at least 4 cycles of chemotherapy Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1 Exclusion Criteria: Small cell lung cancer (SCLC) or mixed SCLC and NSCLC Central nervous system (CNS) metastases Malignancy other than NSCLC Palliative radiotherapy for bone lesions inside the thorax Prior radiotherapy of bone marrow Known to be positive for hepatitis B surface antigen (HbsAg), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) Life expectancy < 6 months Woman of child-bearing potential who is pregnant or is breast feeding or who is not consenting to use highly effective methods of birth control during treatment and for an additional 6 months after the last administration of the protocol specified treatment Man with a partner of childbearing potential who does not consent to use highly effective methods of birth control during treatment and for an additional 6 months after the last administration of the protocol specified treatment Subject has known sensitivity to any of the products to be administered during the study, including mammalian cell derived drug products Other inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABP 215<br>Participants received 15 mg/kg ABP 215 administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles. | Drug: Carboplatin<br>* Administered at an area under the concentration-time curve (AUC) 6 by IV infusion Q3W<br>* Other names: Paraplatin;Drug: Paclitaxel<br>* Administered 200 mg/m² IV Q3W<br>* Other names: Taxol;Drug: ABP 215<br>* Administered 15 mg/kg Q3W by IV infusion<br>|
| Active Comparator: Bevacizumab<br>Participants received bevacizumab 15 mg/kg administered as an intravenous (IV) infusion every 3 weeks (Q3W) for 6 cycles and carboplatin and paclitaxel chemotherapy Q3W for at least 4 and not more than 6 cycles. | Drug: Carboplatin<br>* Administered at an area under the concentration-time curve (AUC) 6 by IV infusion Q3W<br>* Other names: Paraplatin;Drug: Paclitaxel<br>* Administered 200 mg/m² IV Q3W<br>* Other names: Taxol;Drug: Bevacizumab<br>* Administered 15 mg/kg Q3W by IV infusion<br>* Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Objective Response | Tumor assessments were performed by central, independent, blinded radiologists according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 using computed tomography (CT) or magnetic resonance imaging (MRI) scans of the chest and abdomen. Objective response is defined as a best overall response of partial response (PR) or complete response (CR) as defined by RECIST v1.1. All participants who did not meet the criteria for CR or PR by the end of the study were considered non-responders. CR: Disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes must be reduced in short axis to < 10 mm. PR: Disappearance of all target lesions with persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, and no new lesions, or, at least a 30% decrease in the sum of diameters of target lesions, with no progression of existing non-target lesions and no new lesions. | Disease assessments were performed at weeks 1, 7, 13, 19, and approximately every 9 weeks thereafter. The mean actual follow-up time from randomization was 4.7 and 5.0 months for ABP 215 and bevacizumab, respectively. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response | Duration of response (DOR) was calculated as the time from the first objective response (PR or CR) to disease progression per RECIST v1.1 based on the central, independent, blinded radiologists' review. DOR was only calculated for participants with an objective response. For responders not meeting the criterion for progression by the end of the study, DOR was censored at the date of the last evaluable tumor assessment. Progressive Disease was defined as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm, or, unequivocal progression of existing non-target lesions, or any new lesions. | Disease assessments were performed at weeks 1, 7, 13, 19, and approximately every 9 weeks thereafter. The mean actual follow-up time from randomization was 4.7 and 5.0 months for ABP 215 and bevacizumab, respectively. | 
| Progression-free Survival | Progression-free survival (PFS) was defined as the time from the randomization date to the date of disease progression using RECIST v1.1 based on the central, independent, blinded radiologists' review, or death. Participants who were alive and did not meet the criteria for progression by the end of the study were censored at their last evaluable disease assessment date. Participants with no evaluable tumor assessments after randomization who did not die by the end of the study were censored on the randomization date. Progressive Disease was defined as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm, or, unequivocal progression of existing non-target lesions, or any new lesions. | From randomization until the end of study; The mean actual follow-up time from randomization was 4.7 and 5.0 months for ABP 215 and bevacizumab, respectively. | 
| Number of Participants With Adverse Events | Adverse events (AEs) were graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4, and according to the following scale: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death due to AE. A serious adverse event (SAE) is defined as an AE that meets at least 1 of the following serious criteria: fatal life-threatening required inpatient hospitalization or prolongation of existing hospitalization resulted in persistent or significant disability/incapacity congenital anomaly/birth defect other medically important serious event | up to 19 weeks | 
| Number of Participants Who Developed Anti-drug Antibodies | Two validated assays were used to detect the presence of anti-ABP 215 antibodies. Samples were first tested in an electrochemiluminescence (ECL)- based bridging immunoassay to detect antibodies capable of binding to ABP 215 (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a non-cell based target binding assay to determine neutralizing activity against ABP 215 (Neutralizing Antibody Assay). If a post-dose sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the sample was defined as positive for neutralizing antibodies. | 44 weeks (6 months after end of treatment) | 
| Overall Survival | Overall survival (OS) was defined as the time from the randomization date to date of death. Participants alive at the end of study were censored at the last date known to be alive, derived from dates collected within the study that implied a participant was alive. Participants were followed for survival status during the treatment phase and thereafter every 9 weeks until the end of the clinical study, consent was withdrawn, they were lost to follow-up, died, or had proscribed therapy (eg, commercial bevacizumab, non-study anti-cancer treatment). | From randomization until the end of study; The mean actual follow-up time from randomization was 4.7 and 5.0 months for ABP 215 and bevacizumab, respectively. |