Evaluation of FKB238 and Avastin in Patients With Advanced/Recurrent Non-squamous Non-small Cell Lung Cancer
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Interventions
- Registration Number
- NCT02810457
- Lead Sponsor
- Centus Biotherapeutics Limited
- 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 available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 731
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description FKB238 / paclitaxel / carboplatin FKB238 (bevacizumab) 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. Avastin / paclitaxel / carboplatin Avastin (bevacizumab) 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. FKB238 / paclitaxel / carboplatin 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. FKB238 / paclitaxel / carboplatin Paclitaxel 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. Avastin / paclitaxel / carboplatin Paclitaxel 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. Avastin / paclitaxel / carboplatin 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.
- Primary Outcome Measures
Name Time Method 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) 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.
- Secondary Outcome Measures
Name Time Method 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. 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.
ORR at Week 19 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.
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. 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).
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. 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) 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.
Trial Locations
- Locations (147)
Research Site 5503
🇵🇭Quezon, Philippines
Research Site 8606
🇧🇦Banja Luka, Bosnia and Herzegovina
Research Site 7502
🇹🇭Udon Thani, Thailand
Research Site 7713
🇺🇦Lutsk, Volyns'ka Oblast', Ukraine
Research Site 7709
🇺🇦Dnipropetrovs'k, Ukraine
Research Site 7601
🇹🇷Izmir, Turkey
Research Site 7606
🇹🇷Malatya, Turkey
Research Site 6402
🇷🇸Belgrade, Serbia
Research Site 8401
🇻🇳Hanoi, Ha Noi, Thu Do, Vietnam
Research Site 7706
🇺🇦Odesa, Odes'ka Oblast', Ukraine
Research Site 7503
🇹🇭Khon Kaen, Thailand
Research Site 7605
🇹🇷İzmir, Turkey
Research Site 7708
🇺🇦Kryvyi Rih, Ukraine
Research Site 2603
🇩🇪Kiel, Schleswig-Holstein, Germany
Research Site 6234
🇷🇺Samara, Samarskaya Oblast', Russian Federation
Research Site 2507
🇬🇪Kutaisi, Imereti, Georgia
Research Site 7803 - 21st Century Oncology
🇺🇸Jacksonville, Florida, United States
Research Site 7811 - Innovative Clinical Research Institute
🇺🇸Whittier, California, United States
Research Site 7812 - Joliet Oncology-Hematology Associates, Ltd.
🇺🇸Joliet, Illinois, 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 8507
🇧🇾Brest, Brestskaya Voblasts, Belarus
Research Site 7804 - Tri-County Hematology & Oncology Associates, Inc.
🇺🇸Massillon, Ohio, United States
Research Site 8506
🇧🇾Vitebsk, Vitsyebskaya Voblasts, Belarus
Research Site 8501
🇧🇾Lesnoy, Minskaya Voblasts, Belarus
Research Site 8502
🇧🇾Mogilev, Mahilyowskaya Voblasts, Belarus
Research Site 8605
🇧🇦Tuzla, Tuzlanski Kanton, Bosnia and Herzegovina
Research Site 8603
🇧🇦Sarajevo, Bosnia and Herzegovina
Research Site 3303
🇭🇺Gyula, Békés, Hungary
Research Site 0904
🇧🇬Varna, Bulgaria
Research Site 8604
🇧🇦Zenica, Bosnia and Herzegovina
Research Site 0905
🇧🇬Sofia, Dobrich, Bulgaria
Research Site 1802
🇭🇷Zagreb, Grad Zagreb, Croatia
Research Site 1803
🇭🇷Zagreb, Grad Zagreb, Croatia
Research Site 2503
🇬🇪Tbilisi, Georgia
Research Site 2508
🇬🇪Tbilisi, Georgia
Research Site 2605
🇩🇪Würselen, Nordrhein-Westfalen, Germany
Research Site 2505
🇬🇪Tbilisi, Georgia
Research Site 2604
🇩🇪Hamburg, Germany
Research Site 3004
🇬🇷Athens, Greece
Research Site 3003
🇬🇷Thessaloniki, Greece
Research Site 3005
🇬🇷Thessaloníki, Greece
Research Site 3302
🇭🇺Deszk, Csongrád, Hungary
Research Site 3305
🇭🇺Budapest, Hungary
Research Site 3301
🇭🇺Mátraháza, Heves, Hungary
Research Site 3304
🇭🇺Budapest, Hungary
Research Site 4106
🇮🇹Piacenza, Italy
Research Site 4107
🇮🇹Catania, Italy
Research Site 4301
🇯🇵Fukuyama-shi, Hiroshima, Japan
Research Site 4303
🇯🇵Sasebo-shi, Nagasaki, Japan
Research Site 3306
🇭🇺Zalaegerszeg, Hungary
Research Site 4304
🇯🇵Kumamoto-shi, Kumamoto, Japan
Research Site 6004
🇰🇷Suwon-si, Gyeonggido, Korea, Republic of
Research Site 6005
🇰🇷Busan, Busan Gwang'yeogsi, Korea, Republic of
Research Site 5402
🇵🇪Arequipa, Peru
Research Site 6003
🇰🇷Ulsan, Ulsan Gwang'yeogsi, Korea, Republic of
Research Site 6002
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Research Site 5404
🇵🇪Arequipa, Peru
Research Site 5405
🇵🇪Lima, Peru
Research Site 5502
🇵🇭Manila, National Capital Region, Philippines
Research Site 5506
🇵🇭Manila, National Capital Region, Philippines
Research Site 5705
🇵🇱Toruniak, Kujawsko-pomorskie, Poland
Research Site 5701
🇵🇱Krakow, Malopolskie, Poland
Research Site 5711
🇵🇱Brzozów, Poland
Research Site 5706
🇵🇱Olsztyn, Warminsko-mazurskie, Poland
Research Site 5703
🇵🇱Nowy Sacz, Poland
Research Site 6108
🇷🇴Floreşti, Cluj, Romania
Research Site 6106
🇷🇴Cluj-Napoca, Cluj, Romania
Research Site 6105
🇷🇴Cluj-Napoca, Cluj, Romania
Research Site 6101
🇷🇴Baia Mare, Romania
Research Site 6103
🇷🇴Craiova, Romania
Research Site 6209
🇷🇺Arkhangelsk, Arkhangel'skaya Oblast', Russian Federation
Research Site 6102
🇷🇴Constanta, Romania
Research Site 6107
🇷🇴Iasi, Romania
Research Site 6220
🇷🇺Ufa, Bashkortostan, Respublika, Russian Federation
Research Site 6217
🇷🇺Kuzmolovskiy, Leningradskaya Oblast', Russian Federation
Research Site 6221
🇷🇺Belgorod, Belgorodskaya Oblast', Russian Federation
Research Site 6211
🇷🇺Chelyabinsk, Chelyabinskaya Oblast', Russian Federation
Research Site 6225
🇷🇺Moscow, Moskva, Russian Federation
Research Site 6203
🇷🇺Moscow, Moskva, Russian Federation
Research Site 6230
🇷🇺Novgorod, Nizhegorodskaya Oblast', Russian Federation
Research Site 6219
🇷🇺Saransk, Mordoviya, Respublika, Russian Federation
Research Site 6214
🇷🇺Novosibirsk, Novosibirskaya Oblast', Russian Federation
Research Site 6213
🇷🇺Novosibirsk, Novosibirskaya Oblast', Russian Federation
Research Site 6224
🇷🇺Omsk, Omskaya Oblast', Russian Federation
Research Site 6215
🇷🇺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 6235
🇷🇺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 6201
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Research Site 6210
🇷🇺Sankt Petersburg, Sankt-Peterburg, Russian Federation
Research Site 6202
🇷🇺Sankt Petersburg, Sankt-Peterburg, Russian Federation
Research Site 6228
🇷🇺Kursk, Russian Federation
Research Site 6229
🇷🇺Izhevsk, Udmurtskaya Respublika, Russian Federation
Research Site 6207
🇷🇺Magnitogorsk, Russian Federation
Research Site 6401
🇷🇸Sremska Kamenica, Vojvodina, Serbia
Research Site 6403
🇷🇸Belgrade, Serbia
Research Site 6222
🇷🇺Saint Petersburg, Russian Federation
Research Site 7001
🇪🇸Burgos, Spain
Research Site 6404
🇷🇸Belgrade, Serbia
Research Site 6406
🇷🇸Kragujevac, Šumadijski Okrug, Serbia
Research Site 6405
🇷🇸Belgrade, Serbia
Research Site 7004
🇪🇸A Coruna, A Coruña, Spain
Research Site 7005
🇪🇸Cordoba, Córdoba, Spain
Research Site 7002
🇪🇸Castellón De La Plana, Castellon, Spain
Research Site 7009
🇪🇸Jaen, Jaén, Spain
Research Site 7007
🇪🇸Madrid, Spain
Research Site 7003
🇪🇸Murcia, Spain
Research Site 7404
🇨🇳Douliu, Yunlin, Taiwan
Research Site 7402
🇨🇳New Taipei City, Taipei, Taiwan
Research Site 7008
🇪🇸Murcia, Spain
Research Site 7403
🇨🇳Changhua, Taiwan
Research Site 7401
🇨🇳Taipei, Taiwan
Research Site 7505
🇹🇭Chiang Rai, Thailand
Research Site 7507
🇹🇭Chiang Mai, Thailand
Research Site 7607
🇹🇷Ankara, Turkey
Research Site 7702
🇺🇦Chernivtsi, Chernivets'ka Oblast', Ukraine
Research Site 7705
🇺🇦Kharkiv, Kharkivs'ka Oblast', Ukraine
Research Site 7707
🇺🇦Uzhgorod, Zakarpats'ka Oblast', Ukraine
Research Site 7701
🇺🇦Ivano-Frankivs'k, Ukraine
Research Site 7704
🇺🇦Kyiv, Ukraine
Research Site 8402
🇻🇳Hanoi, Ha Noi, Thu Do, Vietnam
Research Site 8405
🇻🇳Hanoi, Ha Noi, Thu Do, Vietnam
Research Site 7710
🇺🇦Sumy, Ukraine
Research Site 8602
🇧🇦Mostar, Bosnia and Herzegovina
Research Site 1801
🇭🇷Osijek, Osjecko-baranjska Županija, Croatia
Research Site 2504
🇬🇪Bat'umi, Ajaria, Georgia
Research Site 5401
🇵🇪Lima, Peru
Research Site 5504
🇵🇭Makati City, National Capital Region, Philippines
Research Site 8504
🇧🇾Minsk, Minskaya Voblasts, Belarus
Research Site 8601
🇧🇦Sarajevo, Bosnia and Herzegovina
Research Site 7504
🇹🇭Bangkok, Thailand
Research Site 5505
🇵🇭Cebu City, Cebu, Philippines
Research Site 8505
🇧🇾Grodno, Hrodzenskaya Voblasts, Belarus
Research Site 5501
🇵🇭Manila, National Capital Region, Philippines
Research Site 7506
🇹🇭Bangkok, Krung Thep Maha Nakhon, Thailand
Research Site 5708
🇵🇱Lodz, Lódzkie, Poland
Research Site 5702
🇵🇱Elblag, Warminsko-mazurskie, Poland
Research Site 7814 - Compassionate Care Research Group
🇺🇸Fountain Valley, California, United States
Research Site 7810 - Edward H. Kaplan, MD and Associates
🇺🇸Skokie, Illinois, United States
Research Site 7805 - Hematology & Oncology Associates, Inc.
🇺🇸Canton, Ohio, United States
Research Site 7801 - Gabrail Cancer Center
🇺🇸Canton, Ohio, United States
Research Site 7809 - Millennium Oncology
🇺🇸Houston, Texas, United States
Research Site 7501
🇹🇭Hat Yai, Songkhla, Thailand