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

Carcinoma, Non-Small-Cell Lung Clinical Trial

— AVANA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02810457
• Other study ID #: FKB238-002
• Secondary ID: 2015-004104-33
• Status: Completed
• Phase: Phase 3
• Start date: September 7, 2016
• Est. completion date: January 26, 2022

Study information

• Verified date: February 2022
• Source: Centus Biotherapeutics Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 731
• Est. completion date: January 26, 2022
• Est. primary completion date: January 24, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• FKB238 (bevacizumab)

• Avastin (bevacizumab)

• Paclitaxel

• Carboplatin

Locations

Country	Name	City	State
Belarus	Research Site 8507	Brest	Brestskaya Voblasts
Belarus	Research Site 8505	Grodno	Hrodzenskaya Voblasts
Belarus	Research Site 8501	Lesnoy	Minskaya Voblasts
Belarus	Research Site 8504	Minsk	Minskaya Voblasts
Belarus	Research Site 8502	Mogilev	Mahilyowskaya Voblasts
Belarus	Research Site 8506	Vitebsk	Vitsyebskaya Voblasts
Bosnia and Herzegovina	Research Site 8606	Banja Luka
Bosnia and Herzegovina	Research Site 8602	Mostar
Bosnia and Herzegovina	Research Site 8601	Sarajevo
Bosnia and Herzegovina	Research Site 8603	Sarajevo
Bosnia and Herzegovina	Research Site 8605	Tuzla	Tuzlanski Kanton
Bosnia and Herzegovina	Research Site 8604	Zenica
Bulgaria	Research Site 0905	Sofia	Dobrich
Bulgaria	Research Site 0904	Varna
Croatia	Research Site 1801	Osijek	Osjecko-baranjska Županija
Croatia	Research Site 1802	Zagreb	Grad Zagreb
Croatia	Research Site 1803	Zagreb	Grad Zagreb
Georgia	Research Site 2504	Bat'umi	Ajaria
Georgia	Research Site 2507	Kutaisi	Imereti
Georgia	Research Site 2503	Tbilisi
Georgia	Research Site 2505	Tbilisi
Georgia	Research Site 2508	Tbilisi
Germany	Research Site 2604	Hamburg
Germany	Research Site 2603	Kiel	Schleswig-Holstein
Germany	Research Site 2605	Würselen	Nordrhein-Westfalen
Greece	Research Site 3004	Athens
Greece	Research Site 3003	Thessaloniki
Greece	Research Site 3005	Thessaloníki
Hungary	Research Site 3304	Budapest
Hungary	Research Site 3305	Budapest
Hungary	Research Site 3302	Deszk	Csongrád
Hungary	Research Site 3303	Gyula	Békés
Hungary	Research Site 3301	Mátraháza	Heves
Hungary	Research Site 3306	Zalaegerszeg
Italy	Research Site 4107	Catania
Italy	Research Site 4106	Piacenza
Japan	Research Site 4301	Fukuyama-shi	Hiroshima
Japan	Research Site 4304	Kumamoto-shi	Kumamoto
Japan	Research Site 4303	Sasebo-shi	Nagasaki
Korea, Republic of	Research Site 6005	Busan	Busan Gwang'yeogsi
Korea, Republic of	Research Site 6002	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Research Site 6004	Suwon-si	Gyeonggido
Korea, Republic of	Research Site 6003	Ulsan	Ulsan Gwang'yeogsi
Peru	Research Site 5402	Arequipa
Peru	Research Site 5404	Arequipa
Peru	Research Site 5401	Lima
Peru	Research Site 5405	Lima
Philippines	Research Site 5505	Cebu City	Cebu
Philippines	Research Site 5504	Makati City	National Capital Region
Philippines	Research Site 5501	Manila	National Capital Region
Philippines	Research Site 5502	Manila	National Capital Region
Philippines	Research Site 5506	Manila	National Capital Region
Philippines	Research Site 5503	Quezon
Poland	Research Site 5711	Brzozów
Poland	Research Site 5702	Elblag	Warminsko-mazurskie
Poland	Research Site 5701	Krakow	Malopolskie
Poland	Research Site 5708	Lodz	Lódzkie
Poland	Research Site 5703	Nowy Sacz
Poland	Research Site 5706	Olsztyn	Warminsko-mazurskie
Poland	Research Site 5705	Toruniak	Kujawsko-pomorskie
Romania	Research Site 6101	Baia Mare
Romania	Research Site 6105	Cluj-Napoca	Cluj
Romania	Research Site 6106	Cluj-Napoca	Cluj
Romania	Research Site 6102	Constanta
Romania	Research Site 6103	Craiova
Romania	Research Site 6108	Floresti	Cluj
Romania	Research Site 6107	Iasi
Russian Federation	Research Site 6209	Arkhangelsk	Arkhangel'skaya Oblast'
Russian Federation	Research Site 6221	Belgorod	Belgorodskaya Oblast'
Russian Federation	Research Site 6211	Chelyabinsk	Chelyabinskaya Oblast'
Russian Federation	Research Site 6229	Izhevsk	Udmurtskaya Respublika
Russian Federation	Research Site 6228	Kursk
Russian Federation	Research Site 6217	Kuzmolovskiy	Leningradskaya Oblast'
Russian Federation	Research Site 6207	Magnitogorsk
Russian Federation	Research Site 6203	Moscow	Moskva
Russian Federation	Research Site 6225	Moscow	Moskva
Russian Federation	Research Site 6230	Novgorod	Nizhegorodskaya Oblast'
Russian Federation	Research Site 6213	Novosibirsk	Novosibirskaya Oblast'
Russian Federation	Research Site 6214	Novosibirsk	Novosibirskaya Oblast'
Russian Federation	Research Site 6215	Omsk	Omskaya Oblast'
Russian Federation	Research Site 6224	Omsk	Omskaya Oblast'
Russian Federation	Research Site 6208	Orenburg	Orenburgskaya Oblast'
Russian Federation	Research Site 6223	Rostov-on-Don	Rostovskaya Oblast'
Russian Federation	Research Site 6205	Ryazan'	Ryazanskaya Oblast'
Russian Federation	Research Site 6201	Saint Petersburg	Sankt-Peterburg
Russian Federation	Research Site 6212	Saint Petersburg	Sankt-Peterburg
Russian Federation	Research Site 6216	Saint Petersburg	Sankt-Peterburg
Russian Federation	Research Site 6222	Saint Petersburg
Russian Federation	Research Site 6235	Saint Petersburg	Sankt-Peterburg
Russian Federation	Research Site 6234	Samara	Samarskaya Oblast'
Russian Federation	Research Site 6202	Sankt Petersburg	Sankt-Peterburg
Russian Federation	Research Site 6210	Sankt Petersburg	Sankt-Peterburg
Russian Federation	Research Site 6219	Saransk	Mordoviya, Respublika
Russian Federation	Research Site 6220	Ufa	Bashkortostan, Respublika
Serbia	Research Site 6402	Belgrade
Serbia	Research Site 6403	Belgrade
Serbia	Research Site 6404	Belgrade
Serbia	Research Site 6405	Belgrade
Serbia	Research Site 6406	Kragujevac	Šumadijski Okrug
Serbia	Research Site 6401	Sremska Kamenica	Vojvodina
Spain	Research Site 7004	A Coruna	A Coruña
Spain	Research Site 7001	Burgos
Spain	Research Site 7002	Castellón De La Plana	Castellon
Spain	Research Site 7005	Cordoba	Córdoba
Spain	Research Site 7009	Jaen	Jaén
Spain	Research Site 7007	Madrid
Spain	Research Site 7003	Murcia
Spain	Research Site 7008	Murcia
Taiwan	Research Site 7403	Changhua
Taiwan	Research Site 7404	Douliu	Yunlin
Taiwan	Research Site 7402	New Taipei City	Taipei
Taiwan	Research Site 7401	Taipei
Thailand	Research Site 7504	Bangkok
Thailand	Research Site 7506	Bangkok	Krung Thep Maha Nakhon
Thailand	Research Site 7507	Chiang Mai
Thailand	Research Site 7505	Chiang Rai
Thailand	Research Site 7501	Hat Yai	Songkhla
Thailand	Research Site 7503	Khon Kaen
Thailand	Research Site 7502	Udon Thani
Turkey	Research Site 7607	Ankara
Turkey	Research Site 7601	Izmir
Turkey	Research Site 7605	Izmir
Turkey	Research Site 7606	Malatya
Ukraine	Research Site 7702	Chernivtsi	Chernivets'ka Oblast'
Ukraine	Research Site 7709	Dnipropetrovs'k
Ukraine	Research Site 7701	Ivano-Frankivs'k
Ukraine	Research Site 7705	Kharkiv	Kharkivs'ka Oblast'
Ukraine	Research Site 7708	Kryvyi Rih
Ukraine	Research Site 7704	Kyiv
Ukraine	Research Site 7713	Lutsk	Volyns'ka Oblast'
Ukraine	Research Site 7706	Odesa	Odes'ka Oblast'
Ukraine	Research Site 7710	Sumy
Ukraine	Research Site 7707	Uzhgorod	Zakarpats'ka Oblast'
United States	Research Site 7801 - Gabrail Cancer Center	Canton	Ohio
United States	Research Site 7805 - Hematology & Oncology Associates, Inc.	Canton	Ohio
United States	Research Site 7814 - Compassionate Care Research Group	Fountain Valley	California
United States	Research Site 7809 - Millennium Oncology	Houston	Texas
United States	Research Site 7803 - 21st Century Oncology	Jacksonville	Florida
United States	Research Site 7812 - Joliet Oncology-Hematology Associates, Ltd.	Joliet	Illinois
United States	Research Site 7804 - Tri-County Hematology & Oncology Associates, Inc.	Massillon	Ohio
United States	Research Site 7813 - Trinity Cancer Care Center	Minot	North Dakota
United States	Research Site 7806 - Vista Oncology Inc. PS	Olympia	Washington
United States	Research Site 7810 - Edward H. Kaplan, MD and Associates	Skokie	Illinois
United States	Research Site 7811 - Innovative Clinical Research Institute	Whittier	California
Vietnam	Research Site 8401	Hanoi	Ha Noi, Thu Do
Vietnam	Research Site 8402	Hanoi	Ha Noi, Thu Do
Vietnam	Research Site 8405	Hanoi	Ha Noi, Thu Do

Sponsors (1)

Lead Sponsor	Collaborator
Centus Biotherapeutics Limited

Countries where clinical trial is conducted

United States,  Vietnam,  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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serum Trough Concentration (Ctrough)	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.	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.
Other	Proportion of Patients Developing Anti-drug Antibodies (ADAs)	The ADA levels were summarized at baseline and post-baseline time points using descriptive statistics.	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.
Other	Adverse Events (AEs)		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.
Other	Vital Signs		Up to approximately 30 days after last dose of study treatment.
Other	Hematology		Up to approximately 30 days after last dose of study treatment.
Other	Clinical Chemistry		Up to approximately 30 days after last dose of study treatment.
Other	Urinalysis		Up to approximately 30 days after last dose of study treatment.
Other	Electrocardiogram		Up to approximately 30 days after last dose of study treatment.
Other	Eastern Collaborative Oncology Group Performance Status		Up to approximately 30 days after last dose of study treatment.
Other	Physical Examination		Up to approximately 30 days after last dose of study treatment.
Primary	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)	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.	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.
Secondary	ORR at 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.	From the date of randomization up to Week 19.
Secondary	Progression-free Survival (PFS)	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.	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.
Secondary	Overall Survival (OS)	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.	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.
Secondary	Duration Of Response (DOR)	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.	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.
Secondary	Disease Control Rate (DCR) Assessed as the Proportion of Patients With a BOR of Either CR, PR, SD or NED	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).	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.