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Evaluation of FKB238 and Avastin in Patients With Advanced/Recurrent Non-squamous Non-small Cell Lung Cancer (AVANA)

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ClinicalTrials.gov Identifier: NCT02810457
Recruitment Status : Active, not recruiting
First Posted : June 23, 2016
Results First Posted : March 19, 2020
Last Update Posted : March 19, 2020
Sponsor:
Information provided by (Responsible Party):
Centus Biotherapeutics Limited

Tracking Information
First Submitted Date  ICMJE June 3, 2016
First Posted Date  ICMJE June 23, 2016
Results First Submitted Date  ICMJE January 24, 2020
Results First Posted Date  ICMJE March 19, 2020
Last Update Posted Date March 19, 2020
Actual Study Start Date  ICMJE September 7, 2016
Actual Primary Completion Date January 24, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 2, 2020)
Overall Response Rate (ORR) Assessed as the Proportion of Patients With a Best Overall Response (BOR) of Either Complete Response (CR) or Partial Response (PR) [ Time Frame: Until data cut-off, which occurred 12 months after randomization of the last patient enrolled, for a total estimated period of time of up to approximately 30 months. ]
The primary variable in this study was ORR, defined as the proportion of patients with a BOR of CR or PR (by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)). A BOR was defined as the best response (in the order of CR, PR, stable disease (SD), no evidence of disease (NED), progressive disease (PD), and not evaluable (NE)) among all post-baseline disease assessments that occurred until progression, or last evaluable assessment in the absence of progression prior to the initiation of subsequent anti-cancer therapy, irrespective of whether or not patients discontinued the study treatment. The 95% Pearson-Clopper confidence interval (CI) of ORR for each treatment arm was provided. Per RECIST v1.1 for target lesions and assessed by computed tomography (CT) or, if contraindicated, magnetic resonance imaging (MRI): CR=disappearance of all target lesions; PR=at least 30% decrease from baseline in the sum of diameters of target lesions. Overall Response=CR+PR.
Original Primary Outcome Measures  ICMJE
 (submitted: June 20, 2016)
Overall Response Rate (ORR) assessed as the proportion of subjects with a best overall response (BOR) of either Complete Response (CR) or Partial Response (PR) [ Time Frame: Up to approximately 12 months after randomisation of the last patient enrolled ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 2, 2020)
  • ORR at Week 19 [ Time Frame: From the date of randomization up to Week 19. ]
    ORR (by RECIST v1.1) at Week 19 was defined as the proportion of patients with a BOR of CR or PR assessed at Week 19. Only tumor assessments performed up until 19 weeks (i.e. Week 18 assessment + 7 day assessment window) from randomization were considered in this analysis. Per RECIST v1.1 for target lesions and assessed by CT or, if contraindicated, MRI: CR=disappearance of all target lesions; PR=at least 30% decrease from baseline in the sum of diameters of target lesions. Overall Response=CR+PR.
  • Progression-free Survival (PFS) [ Time Frame: Until data cut-off, which occurred 12 months after randomization of the last patient enrolled, for a total estimated period of time of up to approximately 30 months. ]
    The event of interest for PFS was defined as the interval from the date of randomization until first documented disease progression or death from any cause, whichever occurs first. Disease progression was based on tumor assessments according to RECIST v1.1 criteria. The items of the overall response CR, PR, SD and NED were taken as progression-free whereas PD denoted disease progression. PFS was summarized using Kaplan-Meier estimates of the quartiles for each treatment arm, and 95% CIs for the medians were calculated. Per RECIST v1.1 for target lesions and assessed by CT or, if contraindicated, MRI: PD=at least a 20% increase in the sum of the longest diameter of target lesions, unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions.
  • Overall Survival (OS) [ Time Frame: Until data cut-off, which occurred 12 months after randomization of the last patient enrolled, for a total estimated period of time of up to approximately 30 months. ]
    The event of interest was defined as death from any cause. OS was defined as the interval from date of randomization until the date of death due to any cause. OS was summarized using Kaplan-Meier estimates of the quartiles for each treatment arm, and 95% CIs for the medians were calculated.
  • Duration Of Response (DOR) [ Time Frame: Until data cut-off, which occurred 12 months after randomization of the last patient enrolled, for a total estimated period of time of up to approximately 30 months. ]
    DOR was evaluated in this study as a secondary efficacy endpoint. Only the patients defined as responders in the primary analysis of ORR were taken into account for the analysis of DOR. The event of interest was defined as first documented disease progression or death due to any reason, whichever occurred first. DOR was defined as the interval from the first documented response (as defined per RECIST v1.1) until the earlier date of the first documented disease progression or death due to any reason. The date of first documented response was taken as the date of the first tumor assessment with an overall visit response of CR or PR. Per RECIST v1.1 for target lesions and assessed by CT or, if contraindicated, MRI: CR=disappearance of all target lesions; PR=at least 30% decrease from baseline in the sum of diameters of target lesions. DOR was calculated in units of months.
  • Disease Control Rate (DCR) Assessed as the Proportion of Patients With a BOR of Either CR, PR, SD or NED [ Time Frame: Until data cut-off, which occurred 12 months after randomization of the last patient enrolled, for a total estimated period of time of up to approximately 30 months. ]
    The DCR was defined as the proportion of patients defined as responders. The number and percentage of responders and non-responders and the 95% Pearson-Clopper CI of DCR for each treatment arm was provided. The odds ratio for treatment (FKB238 arm versus Avastin arm) and the corresponding 95% Wald CI were produced based on a logistic regression analysis of DCR. Per RECIST v1.1 for target lesions and assessed by CT or, if contraindicated, MRI: CR=disappearance of all target lesions; PR=at least 30% decrease from baseline in the sum of diameters of target lesions; SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study. DCR=CR+PR+SD (≥ 6 weeks).
Original Secondary Outcome Measures  ICMJE
 (submitted: June 20, 2016)
  • Progression-free Survival [ Time Frame: Up to approximately 12 months after randomisation of the last patient enrolled ]
  • Overall Survival [ Time Frame: Up to approximately 12 months after randomisation of the last patient enrolled ]
  • Duration Of Response [ Time Frame: Up to approximately 12 months after randomisation of the last patient enrolled ]
  • Disease Control Rate (DCR) assessed as the proportion of subjects with a best overall response (BOR) of either Complete Response (CR), Partial Response (PR) or Stable Disease (SD) [ Time Frame: Up to approximately 12 months after randomisation of the last patient enrolled ]
Current Other Pre-specified Outcome Measures
 (submitted: March 2, 2020)
  • Serum Trough Concentration (Ctrough) [ Time Frame: Cycle 1 Day 1 (pre- and post-infusion), Cycle 2 Day 1 (pre), Cycle 4 Day 1 (pre and post), Cycle 6 Day 1 (pre), discontinuation visit, and every 12 weeks (up to 1 year [±14 days] after randomisation) until death, or the patient was lost to follow-up. ]
    Ctrough (pre-infusion) and serum maximum concentration (Cmax; at completion of infusion) were compared between treatment arms and time points, and descriptive statistics provided. Ctrough and Cmax concentrations were summarized using the pharmacokinetics (PK) population for each visit at which samples were taken. The pre-dose serum concentrations at Cycles 2, 4, and 6 were considered as Ctrough values and the post-dose serum concentrations at Cycles 1 and 4 were considered as Cmax values. PK data at Cycle 1 Day 1 pre-infusion were not calculable and are therefore not presented in the outcome measure data table. Data are only provided for the time points at which the serum trough concentration was measured.
  • Proportion of Patients Developing Anti-drug Antibodies (ADAs) [ Time Frame: Pre-dose at Cycles 1, 2, 4 and 6, discontinuation visit, and every 12 weeks (up to 1 year [±14 days] after randomisation) until death, or the patient was lost to follow-up, whichever occurred first. ]
    The ADA levels were summarized at baseline and post-baseline time points using descriptive statistics.
  • Adverse Events (AEs) [ Time Frame: From the time of signature of informed consent, throughout the treatment period and up to and including the 30-days after the last dose of study treatment, for a total estimated period of time of up to approximately 30 months. ]
  • Vital Signs [ Time Frame: Up to approximately 30 days after last dose of study treatment. ]
  • Hematology [ Time Frame: Up to approximately 30 days after last dose of study treatment. ]
  • Clinical Chemistry [ Time Frame: Up to approximately 30 days after last dose of study treatment. ]
  • Urinalysis [ Time Frame: Up to approximately 30 days after last dose of study treatment. ]
  • Electrocardiogram [ Time Frame: Up to approximately 30 days after last dose of study treatment. ]
  • Eastern Collaborative Oncology Group Performance Status [ Time Frame: Up to approximately 30 days after last dose of study treatment. ]
  • Physical Examination [ Time Frame: Up to approximately 30 days after last dose of study treatment. ]
Original Other Pre-specified Outcome Measures
 (submitted: June 20, 2016)
  • Adverse Events (AEs) [ Time Frame: Up to approximately 30 days after last dose of study treatment ]
  • Vital Signs [ Time Frame: Up to approximately 30 days after last dose of study treatment ]
  • Hematology [ Time Frame: Up to approximately 30 days after last dose of study treatment ]
  • Clinical Chemistry [ Time Frame: Up to approximately 30 days after last dose of study treatment ]
  • Urinalysis [ Time Frame: Up to approximately 30 days after last dose of study treatment ]
  • Electrocardiogram [ Time Frame: Up to approximately 30 days after last dose of study treatment ]
  • Eastern Collaborative Oncology Group Performance Status [ Time Frame: Up to approximately 30 days after last dose of study treatment ]
  • Physical Examination [ Time Frame: Up to approximately 30 days after last dose of study treatment ]
  • Proportion of Patients Developing Anti-drug Antibodies (ADAs) [ Time Frame: Up to approximately 12 months after randomisation of the last patient enrolled ]
  • Serum trough concentration [ Time Frame: Up to approximately 12 months after randomisation of the last patient enrolled ]
 
Descriptive Information
Brief Title  ICMJE Evaluation of FKB238 and Avastin in Patients With Advanced/Recurrent Non-squamous Non-small Cell Lung Cancer
Official Title  ICMJE A Randomised, Parallel, Double Blinded Study to Compare the Efficacy and Safety of FKB238 to Avastin® In 1st Line Treatment for Patients With Advanced/Recurrent Non Squamous NSCLC in Combination of Paclitaxel and Carboplatin
Brief Summary The purpose of this research study is to compare the effectiveness and safety of FKB238 against Avastin® in men and women with advanced/recurrent non squamous non-small cell lung cancer
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Non-Small-Cell Lung
Intervention  ICMJE
  • Drug: FKB238 (bevacizumab)
  • Drug: Avastin (bevacizumab)
  • Drug: Paclitaxel
  • Drug: Carboplatin
Study Arms  ICMJE
  • Experimental: FKB238 / paclitaxel / carboplatin

    Drug: FKB238:

    15 mg/kg IV infusion on Day 1 of each 21-day cycle.

    Drug: Paclitaxel:

    200 mg/m2 IV infusion on Day 1 of each 21-day cycle for at least 4 and no more than 6 cycles.

    Drug: Carboplatin:

    Area Under Curve (AUC) = 6.0 IV infusion on Day 1 of each 21-day cycle for at least 4 and no more than 6 cycles.

    Interventions:
    • Drug: FKB238 (bevacizumab)
    • Drug: Paclitaxel
    • Drug: Carboplatin
  • Active Comparator: Avastin / paclitaxel / carboplatin

    Drug: Avastin:

    15 mg/kg IV infusion on Day 1 of each 21-day cycle.

    Drug: Paclitaxel:

    200 mg/m2 IV infusion on Day 1 of each 21-day cycle for at least 4 and no more than 6 cycles.

    Drug: Carboplatin:

    AUC = 6.0 IV infusion on Day 1 of each 21-day cycle for at least 4 and no more than 6 cycles.

    Interventions:
    • Drug: Avastin (bevacizumab)
    • Drug: Paclitaxel
    • Drug: Carboplatin
Publications * Syrigos K, Abert I, Andric Z, Bondarenko IN, Dvorkin M, Galic K, Galiulin R, Kuchava V, Sriuranpong V, Trukhin D, Zhavrid E, Fu D, Kassalow LM, Jones S, Bashir Z; AVANA Investigators. Efficacy and Safety of Bevacizumab Biosimilar FKB238 Versus Originator Bevacizumab: Results from AVANA, a Phase III Trial in Patients with Non-Squamous Non-Small-Cell Lung Cancer (non-sq-NSCLC). BioDrugs. 2021 Jul 15. doi: 10.1007/s40259-021-00489-4. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 1, 2018)
731
Original Estimated Enrollment  ICMJE
 (submitted: June 20, 2016)
730
Estimated Study Completion Date  ICMJE February 2022
Actual Primary Completion Date January 24, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients aged 18 years or older
  • Newly diagnosed advanced (stage IV) /recurrent non-squamous NSCLC for which they had not received any systemic anti-cancer therapy for metastatic disease
  • Histologically or cytologically confirmed diagnosis of predominantly non-squamous NSCLC
  • Existence of at least 1 measurable lesion by RECIST v1.1
  • Adequate hematological, renal and liver function
  • Eastern Collaborative Oncology Group Performance Status (ECOG PS) 0 or 1
  • Life expectancy longer than 6 months

Exclusion Criteria:

  • Small cell lung cancer (SCLC) or combination SCLC and NSCLC. Squamous-cell tumors and mixed adenosquamous carcinomas of predominantly squamous nature
  • Any unresolved toxicities from prior systemic therapy
  • Known sensitizing epidermal growth factor receptor (EGFR) mutations or echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation positive mutations
  • Previous dosing with vascular endothelial growth factor (VEGF) inhibitor
  • Known hypersensitivity to any excipients of the Investigational Products (IPs) and combination chemotherapy
  • Use of prohibited concomitant medication
  • Known Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV) infection
  • Fertile men or women of childbearing potential not using adequate contraception.

Other inclusion/exclusion criteria may apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belarus,   Bosnia and Herzegovina,   Bulgaria,   Croatia,   Georgia,   Germany,   Greece,   Hungary,   Italy,   Japan,   Korea, Republic of,   Peru,   Philippines,   Poland,   Romania,   Russian Federation,   Serbia,   Spain,   Taiwan,   Thailand,   Turkey,   Ukraine,   United States,   Vietnam
Removed Location Countries Canada
 
Administrative Information
NCT Number  ICMJE NCT02810457
Other Study ID Numbers  ICMJE FKB238-002
2015-004104-33 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Centus Biotherapeutics Limited
Study Sponsor  ICMJE Centus Biotherapeutics Limited
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Centus Biotherapeutics Limited Centus Biotherapeutics Limited
PRS Account Centus Biotherapeutics Limited
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP