Last reviewed · How we verify

NCT02810457: AVANA

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

Completed Phase 3 Results posted Last updated 10 March 2022
What this trial tests

Phase 3 trial testing FKB238 (bevacizumab) in Carcinoma, Non-Small-Cell Lung in 731 participants. Completed in 26 January 2022.

Timeline
7 September 2016
Primary endpoint
24 January 2019
26 January 2022

Quick facts

Lead sponsorCentus Biotherapeutics Limited
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment731
Start date7 September 2016
Primary completion24 January 2019
Estimated completion26 January 2022
Sites147 locations across Italy, Japan, Taiwan, Vietnam, Poland, South Korea, Philippines, Croatia

Drugs / interventions tested

Conditions studied

Sponsor

Centus Biotherapeutics Limited — full company profile →

Who can join

18 and older, any sex, with Carcinoma, Non-Small-Cell Lung. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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) Primary · 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 s

GroupValue95% CI
FKB238 / Paclitaxel / Carboplatin51.646.38 – 56.89
Avastin / Paclitaxel / Carboplatin53.748.43 – 58.87
ORR at Week 19 Secondary · 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.

GroupValue95% CI
FKB238 / Paclitaxel / Carboplatin47.842.57 – 53.07
Avastin / Paclitaxel / Carboplatin51.045.71 – 56.18
Progression-free Survival (PFS) Secondary · 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 contraindicate

GroupValue95% CI
FKB238 / Paclitaxel / Carboplatin7.727.46 – 7.98
Avastin / Paclitaxel / Carboplatin7.626.90 – 7.82
Overall Survival (OS) Secondary · 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.

GroupValue95% CI
FKB238 / Paclitaxel / Carboplatin14.1312.52 – 16.56
Avastin / Paclitaxel / Carboplatin16.9514.65 – 19.02
Duration Of Response (DOR) Secondary · 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

GroupValue95% CI
FKB238 / Paclitaxel / Carboplatin6.475.39 – 7.69
Avastin / Paclitaxel / Carboplatin6.314.93 – 7.29
Disease Control Rate (DCR) Assessed as the Proportion of Patients With a BOR of Either CR, PR, SD or NED Secondary · 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

GroupValue95% CI
FKB238 / Paclitaxel / Carboplatin87.683.81 – 90.84
Avastin / Paclitaxel / Carboplatin87.583.64 – 90.68
Serum Trough Concentration (Ctrough) Secondary · 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 m

Cycle 1, Day 1 end of infusion
GroupValue95% CI
FKB238 / Paclitaxel / Carboplatin255.15± 184.3
Avastin / Paclitaxel / Carboplatin245.11± 206.8
Cycle 2, Day 1 pre-infusion
GroupValue95% CI
FKB238 / Paclitaxel / Carboplatin42.74± 91.9
Avastin / Paclitaxel / Carboplatin48.48± 77.3
Cycle 4, Day 1 pre-infusion
GroupValue95% CI
FKB238 / Paclitaxel / Carboplatin77.16± 69.4
Avastin / Paclitaxel / Carboplatin83.26± 85.5
Cycle 4, Day 1 end of infusion
GroupValue95% CI
FKB238 / Paclitaxel / Carboplatin339.91± 91.3
Avastin / Paclitaxel / Carboplatin373.92± 51.6
Cycle 6, Day 1 pre-infusion
GroupValue95% CI
FKB238 / Paclitaxel / Carboplatin87.25± 124.5
Avastin / Paclitaxel / Carboplatin108.22± 69.8
Proportion of Patients Developing Anti-drug Antibodies (ADAs) Secondary · 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.

ADA prevalence (ADA positive, baseline or post)
GroupValue95% CI
FKB238 / Paclitaxel / Carboplatin3.0
Avastin / Paclitaxel / Carboplatin3.0
Treatment-emergent ADA positive (ADA incidence)
GroupValue95% CI
FKB238 / Paclitaxel / Carboplatin2.3
Avastin / Paclitaxel / Carboplatin2.3

Adverse events — posted to ClinicalTrials.gov

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. All ongoing and any new AEs/serious AEs (SAEs) identified during the 30 days after last dose were followed to resolution unless the event was considered by the investigator to be unlikely to resolve, or if the patient was lost to follow-up.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

FKB238 / Paclitaxel / Carboplatin
Serious: 91/362 (25%)
Deaths: 195/362
Avastin / Paclitaxel / Carboplatin
Serious: 95/366 (26%)
Deaths: 177/366

Serious adverse events (98 terms)

ReactionSystemFKB238 / Paclitaxel / Carb…Avastin / Paclitaxel / Car…
NeutropeniaBlood and lymphatic system disorders
PneumoniaInfections and infestations
AnaemiaBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
DeathGeneral disorders
PneumothoraxRespiratory, thoracic and mediastinal disorders
Acute coronary syndromeCardiac disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
Neutrophil count decreasedInvestigations
Cerebrovascular accidentNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Pulmonary haemorrhageRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
PancytopeniaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
Cardio-respiratory arrestCardiac disorders
General physical health deteriorationGeneral disorders
CholelithiasisHepatobiliary disorders
CellulitisInfections and infestations
Lung infectionInfections and infestations
SepsisInfections and infestations
White blood cell count decreasedInvestigations
Pathological fractureMusculoskeletal and connective tissue disorders
Other adverse events (37 terms — click to expand)

ReactionSystemFKB238 / Paclitaxel / Carb…Avastin / Paclitaxel / Car…
AlopeciaSkin and subcutaneous tissue disorders
NeutropeniaBlood and lymphatic system disorders
AnaemiaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
AstheniaGeneral disorders
Neuropathy peripheralNervous system disorders
Weight decreasedInvestigations
NauseaGastrointestinal disorders
LeukopeniaBlood and lymphatic system disorders
FatigueGeneral disorders
HypertensionVascular disorders
Decreased appetiteMetabolism and nutrition disorders
ProteinuriaRenal and urinary disorders
Alanine aminotransferase increasedInvestigations
Gamma-glutamyltransferaseInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
Aspartate aminotransferaseInvestigations
DiarrhoeaGastrointestinal disorders
MyalgiaMusculoskeletal and connective tissue disorders
Platelet count decreasedInvestigations
DyspnoeaRespiratory, thoracic and mediastinal disorders
Peripheral sensory neuropathyNervous system disorders
Blood alkaline phosphatase increasedInvestigations
White blood cell count decreasedInvestigations
Neutrophil count decreasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
ParaesthesiaNervous system disorders
VomitingGastrointestinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
HeadacheNervous system disorders
PolyneuropathyNervous system disorders
Back painMusculoskeletal and connective tissue disorders
HyperglycaemiaMetabolism and nutrition disorders
PyrexiaGeneral disorders
ConstipationGastrointestinal disorders
PneumoniaInfections and infestations
Non-cardiac chest painGeneral disorders

Most-reported serious reactions: Neutropenia, Pneumonia, Anaemia, Febrile neutropenia, Pulmonary embolism, Death, Pneumothorax, Acute coronary syndrome.

Data from ClinicalTrials.gov NCT02810457 adverse events section.

Sponsor's own description

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

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Bevacizumab in Colorectal Cancer: Current Role in Treatment and the Potential of Biosimilars.
    Rosen LS, Jacobs IA, Burkes RL. · · 2017 · cited 114× · PMID 28801849 · DOI 10.1007/s11523-017-0518-1
  2. Current treatments for non-small cell lung cancer.
    Guo Q, Liu L, Chen Z, Fan Y, et al · · 2022 · cited 75× · PMID 36033435 · DOI 10.3389/fonc.2022.945102
  3. 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).
    Syrigos K, Abert I, Andric Z, Bondarenko IN, et al · · 2021 · cited 16× · PMID 34264503 · DOI 10.1007/s40259-021-00489-4
  4. Efficacy and Safety of Bevacizumab Biosimilars Compared With Reference Biologics in Advanced Non-small Cell Lung Cancer or Metastatic Colorectal Cancer Patients: A Network Meta-Analysis.
    Xu X, Zhang S, Xu T, Zhan M, et al · · 2022 · cited 8× · PMID 35865968 · DOI 10.3389/fphar.2022.880090
  5. Comparison of efficacy and safety of bevacizumab biosimilar and original bevacizumab in non-squamous non-small cell lung cancer: a systematic review and meta-analysis.
    Xiao X, Zhang G, Sun B, Wang C, et al · · 2022 · cited 6× · PMID 35836506 · DOI 10.21037/tcr-22-71
  6. Biosimilar monoclonal antibodies for cancer treatment in adults.
    Galvao TF, Livinalli A, Lopes LC, Zimmermann IR, et al · · 2024 · cited 2× · PMID 39607013 · DOI 10.1002/14651858.cd013539.pub2

Verify or expand the search:

Other recruiting trials for Carcinoma, Non-Small-Cell Lung

Currently open trials in the same condition.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02810457.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing