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

NCT02810457 | Completed Phase 3 Results DMC

• 2 other identifiers: FKB238-0022015-004104-33
• Study Type: interventional
• Target: 731
• Locations: 24 countries
• Sites: 147

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

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Cancer; Bevacizumab; Carboplatin; Paclitaxel

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• ORR at Week 19

  From the date of randomization up to Week 19.

• Progression-free Survival (PFS)

  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.

• Overall Survival (OS)

  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.

• Duration Of Response (DOR)

  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.

• Disease Control Rate (DCR) Assessed as the Proportion of Patients With a BOR of Either CR, PR, SD or NED

  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.

Other Outcomes (10)

• Serum Trough Concentration (Ctrough)

  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.

• Proportion of Patients Developing Anti-drug Antibodies (ADAs)

  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.

• 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.

Study Arms (2)

FKB238 / paclitaxel / carboplatin

EXPERIMENTAL

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.

Drug: FKB238 (bevacizumab); Drug: Paclitaxel; Drug: Carboplatin

Avastin / paclitaxel / carboplatin

ACTIVE COMPARATOR

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.

Drug: Avastin (bevacizumab); Drug: Paclitaxel; Drug: Carboplatin

Interventions

FKB238 (bevacizumab) DRUG

FKB238 / paclitaxel / carboplatin

Avastin (bevacizumab) DRUG

Avastin / paclitaxel / carboplatin

Paclitaxel DRUG

Avastin / paclitaxel / carboplatin; FKB238 / paclitaxel / carboplatin

Carboplatin DRUG

Avastin / paclitaxel / carboplatin; FKB238 / paclitaxel / carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centus Biotherapeutics Limited: lead

Study Sites (147)

Research Site 7814 - Compassionate Care Research Group

Fountain Valley, California, 92708, United States

Location

Research Site 7811 - Innovative Clinical Research Institute

Whittier, California, 90603, United States

Location

Research Site 7803 - 21st Century Oncology

Jacksonville, Florida, 32204, United States

Location

Research Site 7812 - Joliet Oncology-Hematology Associates, Ltd.

Joliet, Illinois, 60435, United States

Location

Research Site 7810 - Edward H. Kaplan, MD and Associates

Skokie, Illinois, 60076, United States

Location

Research Site 7813 - Trinity Cancer Care Center

Minot, North Dakota, 58701, United States

Location

Research Site 7805 - Hematology & Oncology Associates, Inc.

Canton, Ohio, 44708, United States

Location

Research Site 7801 - Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Research Site 7804 - Tri-County Hematology & Oncology Associates, Inc.

Massillon, Ohio, 44646, United States

Location

Research Site 7809 - Millennium Oncology

Houston, Texas, 77090, United States

Location

Research Site 7806 - Vista Oncology Inc. PS

Olympia, Washington, 98502, United States

Location

Research Site 8507

Brest, Brest Oblast, 224027, Belarus

Location

Research Site 8505

Grodno, Hrodzenskaya Voblasts, 230017, Belarus

Location

Research Site 8501

Lyasny, Minsk Oblast, 223040, Belarus

Location

Research Site 8504

Minsk, Minsk Oblast, 220013, Belarus

Location

Research Site 8502

Mogilev, Mogilyov Oblast, 212018, Belarus

Location

Research Site 8506

Vitebsk, Vitebsk Oblast, 210603, Belarus

Location

Research Site 8605

Tuzla, Tuzlanski Kanton, 75000, Bosnia and Herzegovina

Location

Research Site 8606

Banja Luka, 78000, Bosnia and Herzegovina

Location

Research Site 8602

Mostar, 88000, Bosnia and Herzegovina

Location

Research Site 8601

Sarajevo, 71000, Bosnia and Herzegovina

Location

Research Site 8603

Sarajevo, 71000, Bosnia and Herzegovina

Location

Research Site 8604

Zenica, 72000, Bosnia and Herzegovina

Location

Research Site 0905

Sofia, Dobrich, 9300, Bulgaria

Location

Research Site 0904

Varna, 9010, Bulgaria

Location

Research Site 1802

Zagreb, City of Zagreb, 10 000, Croatia

Location

Research Site 1803

Zagreb, City of Zagreb, 10 000, Croatia

Location

Research Site 1801

Osijek, Osjecko-baranjska Županija, 31 000, Croatia

Location

Research Site 2504

Batumi, Adjara, 6010, Georgia

Location

Research Site 2507

Kutaisi, Imereti, 4600, Georgia

Location

Research Site 2503

Tbilisi, 0112, Georgia

Location

Research Site 2505

Tbilisi, 0159, Georgia

Location

Research Site 2508

Tbilisi, 0186, Georgia

Location

Research Site 2605

Würselen, North Rhine-Westphalia, 52146, Germany

Location

Research Site 2603

Kiel, Schleswig-Holstein, 24105, Germany

Location

Research Site 2604

Hamburg, 22081, Germany

Location

Research Site 3004

Athens, 11527, Greece

Location

Research Site 3003

Thessaloniki, 56403, Greece

Location

Research Site 3005

Thessaloniki, 57010, Greece

Location

Research Site 3303

Gyula, Bekes County, 5700, Hungary

Location

Research Site 3302

Deszk, Csongrád megye, 6772, Hungary

Location

Research Site 3301

Mátraháza, Heves County, 3233, Hungary

Location

Research Site 3305

Budapest, 1121, Hungary

Location

Research Site 3304

Budapest, Hungary

Location

Research Site 3306

Zalaegerszeg, 8900, Hungary

Location

Research Site 4107

Catania, 95126, Italy

Location

Research Site 4106

Piacenza, 29100, Italy

Location

Research Site 4301

Fukuyama-shi, Hiroshima, Japan

Location

Research Site 4304

Kumamoto, Kumamoto, Japan

Location

Research Site 4303

Sasebo-shi, Nagasaki, Japan

Location

Research Site 5402

Arequipa, 054, Peru

Location

Research Site 5404

Arequipa, 054, Peru

Location

Research Site 5401

Lima, 27, Peru

Location

Research Site 5405

Lima, 41, Peru

Location

Research Site 5505

Cebu City, Cebu, 6000, Philippines

Location

Research Site 5504

Makati City, National Capital Region, 1229, Philippines

Location

Research Site 5501

Manila, National Capital Region, 1000, Philippines

Location

Research Site 5502

Manila, National Capital Region, 1000, Philippines

Location

Research Site 5506

Manila, National Capital Region, 1000, Philippines

Location

Research Site 5503

Quezon, 1112, Philippines

Location

Research Site 5705

Toruniak, Kuyavian-Pomeranian Voivodeship, 87-100, Poland

Location

Research Site 5701

Krakow, Lesser Poland Voivodeship, 31-826, Poland

Location

Research Site 5708

Lodz, Lódzkie, 93-513, Poland

Location

Research Site 5702

Elblag, Warmian-Masurian Voivodeship, 82-300, Poland

Location

Research Site 5706

Olsztyn, Warmian-Masurian Voivodeship, 10-357, Poland

Location

Research Site 5711

Brzozów, 36-200, Poland

Location

Research Site 5703

Nowy Sącz, 33-300, Poland

Location

Research Site 6105

Cluj-Napoca, Cluj, 400058, Romania

Location

Research Site 6106

Cluj-Napoca, Cluj, 400352, Romania

Location

Research Site 6108

Floreşti, Cluj, 407280, Romania

Location

Research Site 6101

Baia Mare, 430031, Romania

Location

Research Site 6102

Constanța, 900591, Romania

Location

Research Site 6103

Craiova, 200385, Romania

Location

Research Site 6107

Iași, 700106, Romania

Location

Research Site 6209

Arkhangelsk, Arkhangelskaya oblast, 163045, Russia

Location

Research Site 6220

Ufa, Bashkortostan Republic, 450054, Russia

Location

Research Site 6221

Belgorod, Belgorod Oblast, 308010, Russia

Location

Research Site 6211

Chelyabinsk, Chelyabinsk Oblast, 454087, Russia

Location

Research Site 6217

Kuzmolovskiy, Leningradskaya Oblast', 188663, Russia

Location

Research Site 6219

Saransk, Mordoviya, Respublika, 430032, Russia

Location

Research Site 6225

Moscow, Moscow, 105229, Russia

Location

Research Site 6203

Moscow, Moscow, 143423, Russia

Location

Research Site 6230

Novgorod, Nizhny Novgorod Oblast, 603109, Russia

Location

Research Site 6214

Novosibirsk, Novosibirsk Oblast, 630007, Russia

Location

Research Site 6213

Novosibirsk, Novosibirsk Oblast, 630047, Russia

Location

Research Site 6215

Omsk, Omsk Oblast, 644013, Russia

Location

Research Site 6224

Omsk, Omsk Oblast, 644013, Russia

Location

Research Site 6208

Orenburg, Orenburg Oblast, 460021, Russia

Location

Research Site 6223

Rostov-on-Don, Rostov Oblast, 344037, Russia

Location

Research Site 6205

Ryazan, Ryazan Oblast, 390011, Russia

Location

Research Site 6234

Samara, Samara Oblast, 443031, Russia

Location

Research Site 6235

Saint Petersburg, Sankt-Peterburg, 195271, Russia

Location

Research Site 6212

Saint Petersburg, Sankt-Peterburg, 197022, Russia

Location

Research Site 6216

Saint Petersburg, Sankt-Peterburg, 197342, Russia

Location

Research Site 6202

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

Research Site 6210

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

Research Site 6201

Saint Petersburg, Sankt-Peterburg, 198255, Russia

Location

Research Site 6229

Izhevsk, Udmurtiya Republic, 426009, Russia

Location

Research Site 6228

Kursk, 305035, Russia

Location

Research Site 6207

Magnitogorsk, 455001, Russia

Location

Research Site 6222

Saint Petersburg, 198255, Russia

Location

Research Site 6401

Kamenitz, Vojvodina, 21204, Serbia

Location

Research Site 6402

Belgrade, 11000, Serbia

Location

Research Site 6403

Belgrade, 11000, Serbia

Location

Research Site 6404

Belgrade, 11000, Serbia

Location

Research Site 6405

Belgrade, 11070, Serbia

Location

Research Site 6406

Kragujevac, Šumadijski Okrug, 34000, Serbia

Location

Research Site 6005

Busan, Busan Gwang'yeogsi, 49241, South Korea

Location

Research Site 6004

Suwon, Gyeonggido, 16247, South Korea

Location

Research Site 6002

Seoul, Seoul Teugbyeolsi, 06973, South Korea

Location

Research Site 6003

Ulsan, Ulsan Gwang'yeogsi, 44033, South Korea

Location

Research Site 7004

A Coruña, A Coruña, 15009, Spain

Location

Research Site 7002

Castellon, Castellon, 12002, Spain

Location

Research Site 7005

Córdoba, Córdoba, 14004, Spain

Location

Research Site 7009

Jaén, Jaén, 23007, Spain

Location

Research Site 7001

Burgos, 9006, Spain

Location

Research Site 7007

Madrid, 28040, Spain

Location

Research Site 7008

Murcia, 30008, Spain

Location

Research Site 7003

Murcia, 30120, Spain

Location

Research Site 7402

New Taipei City, Taipei, 231, Taiwan

Location

Research Site 7404

Douliu, Yunlin, 64041, Taiwan

Location

Research Site 7403

Changhua, 500, Taiwan

Location

Research Site 7401

Taipei, 10449, Taiwan

Location

Research Site 7506

Bangkok, Bangkok, 10330, Thailand

Location

Research Site 7501

Hat Yai, Changwat Songkhla, 90110, Thailand

Location

Research Site 7504

Bangkok, Thailand

Location

Research Site 7507

Chiang Mai, 50200, Thailand

Location

Research Site 7505

Chiang Rai, 57000, Thailand

Location

Research Site 7503

Khon Kaen, 40000, Thailand

Location

Research Site 7502

Udon Thani, 41330, Thailand

Location

Research Site 7607

Ankara, 06590, Turkey (Türkiye)

Location

Research Site 7605

Izmir, 35100, Turkey (Türkiye)

Location

Research Site 7601

Izmir, 35110, Turkey (Türkiye)

Location

Research Site 7606

Malatya, 44100, Turkey (Türkiye)

Location

Research Site 7702

Chernivtsi, Chernivtsi Oblast, 58013, Ukraine

Location

Research Site 7705

Kharkiv, Kharkivs’ka Oblast’, 61070, Ukraine

Location

Research Site 7706

Odesa, Odesa Oblast, 65055, Ukraine

Location

Research Site 7713

Lutsk, Volyn Oblast, 63000, Ukraine

Location

Research Site 7707

Uzhhorod, Zakarpattia Oblast, 88000, Ukraine

Location

Research Site 7709

Dnipro, 49102, Ukraine

Location

Research Site 7701

Ivano-Frankivsk, 76018, Ukraine

Location

Research Site 7708

Kryvyi Rih, 50048, Ukraine

Location

Research Site 7704

Kyiv, 03115, Ukraine

Location

Research Site 7710

Sumy, 40022, Ukraine

Location

Research Site 8401

Hanoi, Ha Noi, Thu Do, 10000, Vietnam

Location

Research Site 8402

Hanoi, Ha Noi, Thu Do, 10000, Vietnam

Location

Research Site 8405

Hanoi, Ha Noi, Thu Do, 10000, Vietnam

Location

Related Publications (1)

• 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;35(4):417-428. doi: 10.1007/s40259-021-00489-4. Epub 2021 Jul 15.

  PMID: 34264503 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms

Interventions

Bevacizumab; Paclitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Results Point of Contact

• Title: Clinical Trial Information
• Organization: Centus Biotherapeutics Limited

Clinical-Trial@centusbio.com

+353 1 609 7100

Study Officials

• Centus Biotherapeutics Limited

  Centus Biotherapeutics Limited

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2016
• First Posted: June 23, 2016
• Study Start: September 7, 2016
• Primary Completion: January 24, 2019
• Study Completion: January 26, 2022
• Last Updated: March 10, 2022
• Results First Posted: March 19, 2020

Record last verified: 2022-02

Locations

VN (3); JP (3); PH (6); SE (6); BE (6); BU (2); ES (8); GE (5); RU (27); BO (6); US (11); TU (4); KR (4); TH (7); HU (6); UA (10); RO (7); CR (3); IT (2); DE (3); PE (4); TW (4); PL (7); GR (3)