Primary Objective: The primary objective for this study is to compare the efficacy of ABP 215 with bevacizumab.Secondary Objective(s): The secondary objectives are to assess the safety and immunogenicity of ABP 215 compared with bevacizumab.
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Efficacy Criterion:
* Risk ratio of the incidence of overall response rate (ORR)
Secondary outcome
Secondary Efficacy Criteria:
* Risk difference of the incidence of ORR
* Duration of response (DOR)
* Progression-free survival (PFS)
Safety Criteria:
* Treatment-emergent adverse events
* Treatment-emergent serious adverse events
* Incidence of anti-drug antibodies
* Overall survival (OS)
Background summary
Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in both
men and women in the US and the EU. In the US, there are an estimated 226,160
new cases of and 160,340 deaths due to NSCLC in 2012, and in the EU there were
an estimated 265,600 new cases and 236,000 deaths due to NSCLC in 2006
(American Cancer Society, 2012; Ferlay et al, 2007). NSCLC arises from the
epithelial cells of the lung of the central bronchi to terminal alveoli. The
histological type of NSCLC depends on the cells of origin, most commonly
squamous cell carcinoma, large cell carcinoma, and adenocarcinoma. Cigarette
smoking is the primary risk factor for NSCLC, and other risks include exposure
to second hand smoke, family history, radon exposure, and exposure to air
pollution (Hackshaw AK et al, 1997; Matakidou A et al, 2005; Lubin JH and Boice
JD Jr, 1997; Vineis et al, 2004). For patients with metastatic (Stage IV) NSCLC
or recurrent NSCLC following surgery and adjuvant chemotherapy, treatment
usually consists of combination chemotherapy with a platinum-based regimen,
such as cisplatin and gemcitabine or carboplatin and paclitaxel, in repeated
3-week cycles for up to 6 cycles. For patients without squamous cell histology
or a recent history of hemoptysis, addition of the anti-vascular endothelial
growth factor (VEGF) antibody bevacizumab to this regimen improved overall
response rate (ORR) and prolongs progression-free survival (PFS)(Sandler A et
al., 2006; Reck et al, 2009; Hurwitz H and Saini S, 2006).
Based on these and other data, bevacizumab has been approved in the US, EU, and
elsewhere for first-line treatment in patients with advanced or recurrent
nonsquamous NSCLC in combination with platinum-based chemotherapy.
Study objective
Primary Objective: The primary objective for this study is to compare the
efficacy of ABP 215 with bevacizumab.
Secondary Objective(s): The secondary objectives are to assess the safety and
immunogenicity of ABP 215 compared with bevacizumab.
Study design
This is a randomized, double-blind, active-controlled study in adult subjects
with non-small cell lung cancer (NSCLC) receiving first-line chemotherapy with
carboplatin and paclitaxel. Approximately 620 subjects (310 per treatment
group) will be randomized (1:1) to receive investigational product (ABP 215 or
bevacizumab) at a dose of 15 mg/kg administered as an IV infusion Q3W for 6
cycles. All subjects will receive carboplatin and paclitaxel chemotherapy Q3W
for at least 4 and not more than 6 cycles. Subjects will be stratified by
geographic region, Eastern Cooperative Oncology Group (ECOG) performance status
(0 vs 1), and sex.
A subject will remain on the treatment phase until 21 days after the last dose
of investigational product or study specified chemotherapy. Subjects will be
followed for disease progression and overall survival (OS) after completing the
end-of-treatment visit until the end of the clinical study, consent is
withdrawn, they are lost to follow-up, die, or have proscribed therapy (eg,
commercial bevacizumab, non-study anti-cancer treatment).
Intervention
STUDY TREATMENT(S):
Test Product, Dose and Mode of Administration:
ABP 215 administered at a dose of 15 mg/kg IV Q3W.
Reference Therapy, Dose and Mode of Administration:
Bevacizumab administered at a dose of 15 mg/kg IV Q3W.
Chemotherapy:
All subjects will receive carboplatin (target AUC 6) and paclitaxel (starting
dose 200 mg/m2) Q3W after the ABP 215/bevacizumab infusion.
Study burden and risks
ABP 215 is being developed as a biosimilar to bevacizumab, which is currently
marketed and used in the US, EU, and other regions. Bevacizumab is a
recombinant immunoglobulin G1 (IgG1) monoclonal antibody that binds to VEGF and
inhibits the interaction of VEGF with its receptors, VEGF receptor- (VEGFR-) 1
and VEGFR-2, thus inhibiting establishment of new blood vessels necessary for
the maintenance and growth of solid tumors. Bevacizumab is approved in specific
combinations in the US, EU, and other regions for the treatment of patients
with unresectable, locally advanced, recurrent or metastatic nonsquamous NSCLC
as well as metastatic carcinoma of the colon or rectum; metastatic renal cell
carcinoma; and other region-specific indications.
A comprehensive analytical characterization pre-evaluation has shown that beva
cizumab drug product and ABP 215 drug product are comparable, notwithstanding
minor differences that are not expected to affect the safety, efficacy, and
quality of the product.
Adverse events that are reflected in warnings or precautions in the US and/or
EU labeling information, and which may be serious or fatal, include
gastrointestinal perforations, surgery and wound healing
complications, hemorrhage (especially tumor-associated hemorrhage),
nongastrointestinal fistula formation, arterial thromboembolic events, venous
thromboembolic events, congestive heart failure (CHF), neutropenia and
infections, severe hypertension, reversible posterior leukoencephalopathy
syndrome (RPLS), proteinuria, infusion reactions, and ovarian failure (NCCN
Clinical Practice Guidelines in Oncology: Non-small cell lung cancer, 2012;
Kamba T and McDonald DM, 2007; Genentech, Inc. Prescriber*s Information for
Avastin® (bevacizumab), 2012).
A large body of data from clinical studies and postmarketing use support the
effectiveness and safety of bevacizumab in its approved indications. Based on
the data available, it is anticipated that ABP 215 will perform similarly to
bevacizumab in humans and provide similar benefits in patients.
One Amgen Research Center Drive. Parklane Ave. 4130
California 91320
US
One Amgen Research Center Drive. Parklane Ave. 4130
California 91320
US
Listed location countries
Age
Inclusion criteria
Males and females * 18 and < 80 years of age;Histologically or cytologically confirmed non-squamous non-small cell lung cancer ;Stage 4 or recurrent metastatic NSCLC with measurable disease according to modified Response Evaluation Criteria in Solid Tumors (RECIST v1.1). For subjects with recurrent disease, at least 12 months must have elapsed since completing adjuvant chemotherapy. Subjects must have had a baseline scan (computed tomography [CT] or magnetic resonance imaging [MRI]) of the chest and abdomen to assess disease burden before enrolling in study and receiving first-line chemotherapy for NSCLC. If the scan was performed more than 28 days prior to randomization, an additional scan must be obtained;Subjects must be initiating first-line carboplatin/paclitaxel chemotherapy within 8 days after randomization and expected to receive at least 4 cycles of chemotherapy;ECOG performance status score 0 or 1 ;Normal bone marrow function as defined by:;*absolute neutrophil count (ANC) * 1.5 x 109 g/dL (1,500/µL);*platelets * 100 x 109 g/dL (100,000/µL);*hemoglobin * 100 g/L (10.0 g/dL);Adequate hepatic function as defined by:;*total bilirubin < 1.5 × the upper limit of normal (ULN) ;*aspartate aminotransferase (AST) and alanine aminotransferase (ALT); < 3.0 × ULN; ;Adequate renal function as defined by creatinine < 1.5 × ULN;Subjects must sign an IRB/EC-approved informed consent form before any study specific procedures
Exclusion criteria
Small cell lung cancer (SCLC) or mixed SCLC and NSCLC;Mixed adenosquamous carcinomas with a predominantly squamous component;Central nervous system (CNS) metastases;Tumor invading or compressing major blood vessels or tumor cavitation;Malignancy other than NSCLC ;Palliative radiotherapy for bone lesions inside the thorax;Prior radiotherapy of bone marrow;Minor surgical procedure or core biopsy before randomization, or not yet recovered from prior minor surgery;Major surgery within 4 weeks before randomization or not yet recovered from prior surgery;Planned major surgical procedure during the treatment phase;Any of the following before randomization:;· Within 6 months: clinically significant cardiovascular disease; peripheral vascular disease, cerebrovascular accident or transient ischemic attack ;· within 3 months: history of hemoptysis;· at any time: history of thrombotic or hemorrhagic disorders;Proteinuria (with a urine dipstick value of 2+ or above or >100 mg/dl);Coagulation abnormalities or systemic anticoagulation or chronic aspirin therapy. Subjects may receive low dose anti-coagulation therapy for peripheral port patency;Medically uncontrolled hypertension or systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg;Any serious, non-healing unhealed wound or bone fracture;Clinically significant peripheral neuropathy;Significant unplanned weight loss attributed to cancer during 6 months ;Any known co-morbid disease that would increase the risk of toxicity;Known to be positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV), or human immunodeficiency virus (HIV);Recent infection requiring a course of systemic anti-infectives ;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;Other investigational procedures while participating in this study ;Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s), or subject is receiving other investigational agent(s);Subject has known sensitivity to any of the products to be administered during the study, including mammalian cell derived drug products;Subject has previously been randomized in this study;Subject likely to not be available to complete all protocol required study visits or procedures;History or evidence of any other clinically significant disorder, condition
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-000738-36-NL |
| ClinicalTrials.gov | NCT01966003 |
| CCMO | NL45408.060.13 |