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

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Primary Purpose

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Carboplatin

Paclitaxel

ABP 215

Bevacizumab

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer Metastatic

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Research Site
Research Site
Research Site
Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

ABP 215

Bevacizumab

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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

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.

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).

Full Information

NCT ID

NCT01966003

First Posted

October 4, 2013

Last Updated

September 21, 2017

Sponsor

Amgen

Collaborators

Actavis Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01966003

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2017

Overall Recruitment Status

Completed

Study Start Date

November 11, 2013 (Actual)

Primary Completion Date

July 23, 2015 (Actual)

Study Completion Date

July 23, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Amgen

Collaborators

Actavis Inc.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-small Cell Lung Cancer Metastatic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

642 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ABP 215

Arm Type

Experimental

Arm Description

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.

Arm Title

Bevacizumab

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Other Intervention Name(s)

Paraplatin

Intervention Description

Administered at an area under the concentration-time curve (AUC) 6 by IV infusion Q3W

Intervention Type

Drug

Intervention Name(s)

Paclitaxel

Other Intervention Name(s)

Taxol

Intervention Description

Administered 200 mg/m² IV Q3W

Intervention Type

Drug

Intervention Name(s)

ABP 215

Intervention Description

Administered 15 mg/kg Q3W by IV infusion

Intervention Type

Drug

Intervention Name(s)

Bevacizumab

Other Intervention Name(s)

Avastin

Intervention Description

Administered 15 mg/kg Q3W by IV infusion

Primary Outcome Measure Information:

Title

Percentage of Participants With an Objective Response

Description

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.

Time Frame

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 Measure Information:

Title

Duration of Response

Description

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.

Time Frame

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.

Title

Progression-free Survival

Description

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.

Time Frame

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.

Title

Number of Participants With Adverse Events

Description

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

Time Frame

up to 19 weeks

Title

Number of Participants Who Developed Anti-drug Antibodies

Description

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.

Time Frame

44 weeks (6 months after end of treatment)

Title

Overall Survival

Description

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).

Time Frame

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.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

MD

Organizational Affiliation

Amgen

Official's Role

Study Director

Facility Information:

Facility Name

Research Site

City

Bismarck

State/Province

North Dakota

ZIP/Postal Code

58501

Country

United States

Facility Name

Research Site

City

Fremantle

State/Province

Western Australia

ZIP/Postal Code

6160

Country

Australia

Facility Name

Research Site

City

Veliko Tarnovo

State/Province

Veliko Turnovo

ZIP/Postal Code

5000

Country

Bulgaria

Facility Name

Research Site

City

Ruse

ZIP/Postal Code

7003

Country

Bulgaria

12. IPD Sharing Statement

Citations:

PubMed Identifier

30617139

Citation

Thatcher N, Goldschmidt JH, Thomas M, Schenker M, Pan Z, Paz-Ares Rodriguez L, Breder V, Ostoros G, Hanes V. Efficacy and Safety of the Biosimilar ABP 215 Compared with Bevacizumab in Patients with Advanced Nonsquamous Non-small Cell Lung Cancer (MAPLE): A Randomized, Double-blind, Phase III Study. Clin Cancer Res. 2019 Apr 1;25(7):2088-2095. doi: 10.1158/1078-0432.CCR-18-2702. Epub 2019 Jan 7. Erratum In: Clin Cancer Res. 2019 May 15;25(10):3193.

Results Reference

derived

Links:

URL

http://www.amgentrials.com

Description

AmgenTrials clinical trials website

Non-small Cell Lung Cancer Metastatic

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial