A Study of Bemarituzumab (FPA144) Combined With Modified FOLFOX6 (mFOLFOX6) in Gastric/Gastroesophageal Junction Cancer

Gastric Cancer Clinical Trial

— FIGHT  

Official title:

FIGHT: A Phase 2 Randomized, Double-Blind, Controlled Study Evaluating Bemarituzumab (FPA144) and Modified FOLFOX6 in Patients With Previously Untreated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Preceded by Dose-Finding in Phase 1

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03694522
• Other study ID #: FPA144-004 Phase 2
• Secondary ID: 2017-003507-2220
• Status: Completed
• Phase: Phase 2
• Start date: September 14, 2018
• Est. completion date: May 13, 2022

Study information

• Verified date: February 2024
• Source: Five Prime Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main objective of the Phase 2 part of the study is to evaluate the efficacy of bemarituzumab (FPA144), a targeted antibody, in combination with modified FOLFOX6 compared to placebo in combination with modified FOLFOX6 in participants with advanced gastrointestinal cancer.

Description:

Study FPA144-004 is a phase 1/2, multicenter, global, double-blind, randomized, controlled study designed to evaluate the safety, tolerability, efficacy, and pharmacokinetics (PK) of bemarituzumab in combination with mFOLFOX6, compared with placebo in combination with mFOLFOX6, in adults with unresectable, locally advanced, or metastatic gastric cancer including cancer of the gastroesophageal junction (GEJ). This study includes a Phase 1 safety run-in portion and a Phase 2 portion. The Phase 1 safety run-in is an open-label dose-escalation of bemarituzumab + mFOLFOX6 in patients with GI tumors (not FGFR2 selected) that is reported separately (NCT03343301). The Phase 2 portion of the study (to follow the Phase 1 safety run-in) is described in this record.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 155
• Est. completion date: May 13, 2022
• Est. primary completion date: September 23, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Histologically documented gastric or gastroesophageal junctional adenocarcinoma (not amenable to curative therapy)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Adequate hematological, liver and kidney function. Measurable or non-measurable, but evaluable disease using RECIST v1.1
• Fibroblast growth factor receptor 2b (FGFR2b) overexpression as determined by a centrally performed immunohistochemistry tissue test and/or FGFR2 gene amplification as determined by a centrally performed circulating tumor deoxyribonucleic acid (ctDNA) blood based assay
• Candidate for mFOLFOX6 chemotherapy

Key Exclusion Criteria:

• Untreated or symptomatic central nervous system (CNS) metastases
• Clinically significant cardiac disease,
• Peripheral sensory neuropathy >/= Common Terminology Criteria for Adverse Events (CTCAE) Grade 2
• Active infection requiring systemic treatment
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or known active or chronic hepatitis B or C infection
• Prior treatment with any selective inhibitor of the fibroblast growth factor (FGF)-FGFR pathway
• Known abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer
• Known positivity for human epidermal growth factor receptor 2 (HER2)
• Women who are pregnant or breastfeeding Note: Other protocol defined Inclusion/Exclusion criteria may apply

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

Biological:
• Bemarituzumab
Administered by intravenous infusion over approximately 30 minutes

Drug:
• Placebo
Administered by intravenous infusion over approximately 30 minutes
• Modified FOLFOX6
mFOLFOX6 regimen consists of the following: Oxaliplatin 85 mg/m² IV infusion over 120 minutes Leucovorin 400 mg/m² IV infusion over 120 minutes, or 200 mg/m² levo-leucovorin if leucovorin is unavailable 5-fluorouracil (5-FU) 400 mg/m² bolus over approximately 5 minutes then 5-FU 2400 mg/m² as a continuous IV infusion over approximately 48 hours

Locations

Country	Name	City	State
Australia	Chris O'brien Lifehouse	Camperdown
Australia	The Townsville Hospital	Douglas
Australia	Sydney Adventist Hospital	Wahroonga
Belgium	AZ Sint Jan	Brugge
Belgium	CH de l'Ardenne	Libramont
Belgium	CHC Clinique Saint-Joseph	Liege
Belgium	CHU UCL Namur, site Godinne	Yvoir
China	Beijing Cancer Hospital	Beijing
China	Chinese PLA General Hospital	Beijing
China	Sino Japanese Friendship Hospital of Jilin University	Changchun
China	The First Hospital of Jilin University	Changchun
China	Hunan Cancer Hospital	Changsha
China	Xiangya Hospital of Central South University	Changsha
China	Chongqing Daping Hospital	Chongqing
China	Fujian Cancer Hospital	Fuzhou
China	Sir Run Run Shaw Hospital	Hangzhou
China	The First Affiliated Hospital, Zhejiang University	Hangzhou
China	Zhejiang Cancer Hospital	Hangzhou
China	Harbin Medical University Cancer Hopsital	Harbin
China	Anhui Provincial Cancer Hospital	Hefei	Anhui
China	The 81st Hospital of Chinese PLA	Nanjing	Jiangsu
China	Nanton Tumor Hospital	Nantong
China	Fudan University Shanghai Cancer Center	Shanghai
China	Ruijin Hospital Affiliated to Shanghai Jiatong University School of Medicine	Shanghai
China	Shanghai East Hospital	Shanghai
China	Cancer Hospital of Shantou University Medical College	Shantou
China	Liaoning Cancer Hospital	Shenyang
China	Fourth Hospital of Hebei Medical University	Shijiazhuang
China	Shiyan Taihe Hospital	Shiyan	Hubei
China	The Second Affiliated Hospital of Soochow University	Suzhou
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin
China	Wuhan Union Hospital of China	Wuhan	Hubei
China	Henan Cancer Hospital	Zhengzhou
France	CHRU Jean MINJOZ	Besançon
France	Chu Morvan - Institut de Cancerologie	Brest
France	Hopital Nord France Comte - Site Le Mittan	Montbéliard
France	Polyclinique de Gentilly	Nancy
France	CHU de Saint Etienne	Saint-Étienne
France	Centre de Radiotherapie - Clinique Sainte Anne	Strasbourg
France	Centre Paul Strauss	Strasbourg
Germany	Klinik fur Innere Medizin, Shwerpunkt Gastroenterologie, Hamatologie, Onkologie, Nephrologie	Berlin
Germany	Stadtisches Klinikum Braunschweig	Braunschweig
Germany	Krankenhaus Nordwest gGmbH, Institut fur Klinisch-Onkologische Forschung	Frankfurt am Main
Germany	Klinikum Ludwigsburg	Ludwigsburg
Germany	Universitatsmedizin Manheim, II. Medizinische Klinik	Mannheim
Germany	Klinikum Ostalb, Stauferklinikum Schwabisch Gmund, Zentrum fur Innere Medizin	Mutlangen
Germany	Kliniken Nordoberpfalz AG, Klinikum Weiden, Medizinische Klinik I	Oberpfalz
Hungary	Del-Pesti Centrumkorhaz - Orszangos Hematologiai es Infektologiai Intezet, Onkologiai Osztaly	Budapest
Hungary	National Institute of Oncology	Budapest
Hungary	Sugarterapias es Klinikai Onkologaiai Intezet B-A-Z Megyei Korhaz	Miskolc
Hungary	Josa Andras Teaching Hospital	Nyíregyháza
Hungary	University of Pecs, Clinic of Oncotherapy	Pecs
Hungary	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz - Rendelointezet	Szolnok
Italy	AOU Ospedall Riuniti Umberto	Ancona
Italy	AO "S.G. Moscati"	Avellino
Italy	Centro di Riferimento Oncologico	Aviano
Italy	Azienda Ospedaliera Spedali Civili di Brescia-Universita degli Studi Di Brescia	Brescia
Italy	Istituto di Ricovero e Cura a Carattere Scientifico - IRCCS di Candiolo	Candiolo
Italy	Azienda Socio-Sanitaria Territoriale di Cremona	Cremona
Italy	Azienda Ospedaliero Universitaria Caregg - I S.O.D. Oncologia Medica	Firenze
Italy	Ospedale Policlinico S. Martino	Genova
Italy	Ospedale Generale Mater Salutis" - Azienda ULSS n. 21 di Legnago	Legnago
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola
Italy	Istituto Europeo di Oncologia	Milan
Italy	Servizio Oncologia Medica ed Ematologia, AOU dell'Universita	Napoli
Italy	Fondazione Irccs Policlinico San Matteo	Pavia
Italy	Azienda Ospedaliera Universitaria Pisana	Pisa
Italy	Policlinico Universitario Campus Bio-Medico di Roma	Roma
Italy	Fondazione IRCSS Casa Sollievo Della Sofferenza	San Giovanni Rotondo
Italy	ASST della Valtellina e dell'Alto Lario - PO di Sondrio	Sondrio
Italy	A.O.U. Citta della Salute e della Scienza di Torino - Presidio Molinette	Torino
Italy	Azienda Sanitaria Universitaria Integrata de Udine	Udine
Japan	Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital	Bunkyo-Ku
Japan	Hiroshima Citizens Hospital	Hiroshima
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	St. Marianna University School of Medicine Hospital	Kawasaki
Japan	Kagawa University Hospital	Kita-gun	Kagawa
Japan	Japan Community Health Care Organization Kyushu Hospital	Kitakyushu
Japan	The Cancer Institute Hospital of JFCR	Koto-Ku
Japan	Niigata Cancer Center Hospital	Niigata
Japan	Hyogo College of Medicine College Hospital	Nishinomiya
Japan	Osaka General Medical Center	Osaka
Japan	Osaka Medical College Hospital	Osaka
Korea, Republic of	Hallym University Sacred Heart Hospital	Anyang	Gyeonggi-do
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu	North Gyeongsang
Korea, Republic of	Chungnam National University Hospital (CNUH)	Daejeon
Korea, Republic of	Gachon University Gil Medical Center	Incheon	Namdong-gu
Korea, Republic of	Chonbuk National University Hospital	Jeonju	Jeollabuk-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam	Gyeonggi
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Gangnam Severance Hospital, Yonsei University Health System	Seoul	Gangnam
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Korea, Republic of	Yonsei University Health System	Seoul
Korea, Republic of	Ajou University Hospital	Suwon	Gyeonggi
Poland	Beskidzkie Centrum Onkologii - Szpital Miejski im. Jana Pawla II w Bielsku-Bialej	Bielsko-Biala
Poland	Szpital Specjalistyczny w Brzozowie, Podkarpacki Osrodek Onkologiczny	Brzozów
Poland	Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie	Lublin
Poland	SP ZOZ Ministerstwa Spraw Wewnetrznych z Warminsko - Mazurskim Centrum Onkologii	Olsztyn
Poland	Europejskie Centrum Zdrowia Otwock Szpital im. F. Chopina	Otwock
Poland	Lekarz Beata Madej Mruk I Partner. Spolka Partnerska Oddzial nr 1 w Rzesowie	Rzeszów
Poland	Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie Klinika Onkologi I Radioterapii	Warszawa
Poland	Wojskowy Instytut Medyczny, Centralny Szpital Kliniczny Ministerstwa Obronty Narodowej	Warszawa
Portugal	Centro Hospitalar do Baixo Vouga, EPE	Aveiro
Portugal	Hospital de Braga	Braga
Portugal	Hospital Senhora Da Oliveira EPE	Guimarães
Portugal	Centro Hospitalar Universitario do Porto E.P.E	Porto
Portugal	Instituto Portugues de Oncologia do Porto Francisco Gentil E.P.E	Porto
Portugal	Centro Hospitalar de Entre o Douro e Vouga EPE	Santa Maria Da Feira
Portugal	Unidade Local de Saude de Matosinhos EPE	Senhora Da Hora
Romania	Institutul Clinic Fundeni - Clinica Pediatrie	Bucharest
Romania	S.C. Medisprof S.R.L	Cluj Napoca
Romania	Institutul Oncologic, Prof. Dr. I. Chiricuta Cluj-Napoca	Cluj-Napoca
Romania	Spitalul Clinic Judetean de Urgenta ,,Sf. Apostol Andrei" Constanta, Clinica Oncologie Medicala	Constanta
Romania	S.C. Centrul de Oncologie Sf. Nectarie S.R.L., Oncologie Medicala	Craiova
Romania	SC Oncolab SRL, Oncologie	Craiova
Romania	S.C. Oncocenter Oncologie Clinica S.R.L	Timisoara
Spain	Complejo Hospitalario Universitario A Coruna	A Coruña
Spain	Hospital Universitario Fundacion Alcorcon	Alcorcon
Spain	Hospital de la Santa Creu I Sant Pau	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Duran I Reynals - Instituto Catalan de Oncologia	Barcelona
Spain	Hospital General de Catalunya	Barcelona
Spain	Institut Catala d'Oncologia - Hospital Doctor Josep Trueta	Girona
Spain	Hospital Universitari Arnau de Vilanova	Lleida
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda
Spain	Clinica Universidad de Navarra	Pamplona
Spain	Complejo Hospital De Navarra	Pamplona
Spain	Corporacio Sanitaria Parc Tauli	Sabadell
Spain	Hosptial Universitario Virgen Macarena	Servilla
Spain	Hospital Universitario Mutua de Terrassa	Terrassa
Taiwan	China Medical University Hospital	Taichung
Thailand	Faculty of Medicine, Chulalongkorn University	Bankok
Thailand	Chiangrai Prachanukroh Hospital	Chiang Rai
Thailand	Faculty of Medicine, Prince of Sonkla University	Hat Yai
Thailand	Khon Kaen Hospital	Khon Kaen
Thailand	Lampang Cancer Hospital	Lampang
Turkey	Cukurova University Faculty of Medicine Paediatric Nephrology	Adana
Turkey	Ankara Oncology Education and Research Hospital	Ankara
Turkey	Hacettepe Universitesi Tip Fakultesi	Ankara
Turkey	Ondokuz Mayis University Medicine Faculty	Atakum
Turkey	Adnan Menderes Universitesi Uygulama ve Arastirma Hastanesi	Aydin
Turkey	Uludag Universitesi Tip Fakultesi	Bursa
Turkey	Gaziantep Universitesi Tip Fakultesi, Sahinbey Onkoloji Hastanesi	Gaziantep
Turkey	Bezmialem Vakif Universitesi Tip Fakultesi Hastanesi	Istanbul
Turkey	Istanbul Madeniyet Universitesi Tip Fakultesi	Istanbul
Turkey	Istanbul University Cerrahpasa Medical Faculty	Istanbul
Turkey	Ege University Hopsital	Izmir
Turkey	Medical Park Izmir Hastanesi	Izmir
Turkey	Kocaeli Universitesi Tip Fakultesi	Kocaeli
Turkey	Inonu Universitesi Tip Fakultesi Turgut Ozal Tip Merkezi	Malatya
Turkey	Yuzuncuyil Universitesi Tip Fakultesi	Van
United Kingdom	Ninewells Hospital and Medical School	Dundee
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Arlington Cancer Center	Arlington	Texas
United States	St. Luke's Physician Group - St. Luke's Cancer Care Associates	Bethlehem	Pennsylvania
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	UNC- Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Chicago	Chicago	Illinois
United States	Josephine Ford Cancer Center-Henry Ford Cancer Center	Detroit	Michigan
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Marin Cancer Care, Inc-California Cancer Care A Medical Group, Inc	Greenbrae	California
United States	Tennessee Cancer Specialists	Knoxville	Tennessee
United States	Summit Medical Group. Morristown Oncology	Morristown	New Jersey
United States	Yale Cancer Center	New Haven	Connecticut
United States	Oschsner Clinic Foundation	New Orleans	Louisiana
United States	FirstHealth Outpatient Cancer Center	Pinehurst	North Carolina
United States	Hartford Healthcare Cancer Institute at The Hospital of Central Connecticut	Plainville	Connecticut
United States	University of Rochester Medical Center (URMC) - Wilmot Cancer Institute (WCI) (James P. Wilmot Cancer Center)	Rochester	New York
United States	Utah Cancer Specialists (Intermountain Hematology - Oncology Associates) UCS Cancer Center	S. Salt Lake	Utah
United States	Sutter Medical Group	Sacramento	California
United States	UCLA Medical Centre - Santa Monica Hematology and Oncology	Santa Monica	California
United States	Virginia Mason Seattle Main Clinic	Seattle	Washington
United States	Stony Brook Cancer Center	Stony Brook	New York
United States	The Oncology Institute of Tuscon	Tucson	Arizona
United States	University of Arizona Cancer Center	Tucson	Arizona
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	University of Kansas Medical Center	Westwood	Kansas
United States	Westchester Institute For Treatment Of Cancer & Blood Disorders	White Plains	New York
United States	Innovative Clinical Research Institute (ICRI)	Whittier	California

Sponsors (2)

Lead Sponsor	Collaborator
Five Prime Therapeutics, Inc.	Zai Lab (Shanghai) Co., Ltd.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  China,  France,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Poland,  Portugal,  Romania,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)	PFS was defined as time from randomization until the date of radiographic disease progression based on investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or death from any cause, whichever came first. PFS was analyzed using Kaplan-Meier methods. Participants with no progression or death, or who started new anticancer therapy before documented progression or death without documented progression, or who had = 2 consecutive missing tumor assessments before documented progression or death without documented progression were censored on the date of last adequate tumor assessment. Participants with no baseline tumor assessment, were censored at the date of randomization.; The primary efficacy analysis was pre-specified to be conducted after at least 84 PFS events were observed.	From randomization until the primary analysis data cut-off date of 23 September 2020; median time on follow-up was 10.9 months.
Secondary	Overall Survival (OS)	OS is defined as time from randomization until death from any cause. Participants who were lost to follow-up or did not have a date of death were censored at the last date that they were known to be alive. Participants with confirmed death or alive status after the data cutoff date were censored at the data cutoff date. Median OS was estimated using a Kaplan-Meier analysis.	From randomization until the primary analysis data cut-off date of 23 September 2020; median time on follow-up was 10.9 months.
Secondary	Overall Response Rate (ORR)	Tumor response assessment was performed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines. ORR is defined as the percentage of participants who achieved a best overall response (BOR) of either complete response (CR) or partial response (PR) based on investigator assessment of tumor lesions per RECIST v1.1.; CR was defined as the disappearance of all lesions except lymph node short axis < 10 mm; PR was defined as a = 30% reduction in sum of diameters in target lesions.	Tumor assessments were performed every 8 weeks until 12 months and then every 12 weeks thereafter until disease progression or additional anticancer therapy was initiated; the median duration of follow-up time was 10.9 months.
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	TEAEs are defined as adverse events (AEs) that started or worsened from the start of study drug to 28 days after permanent discontinuation of study drug.; A serious AE is defined as any untoward medical occurrence that: Resulted in death; Was life-threatening; Required inpatient hospitalization or prolongation of existing hospitalization; Resulted in persistent or significant disability or incapacity; Was a congenital anomaly or birth defect.; The investigator assessed the causality/relationship between study treatment and each AE, and assessed the severity of each AE according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0 on a scale from mild (Grade 1), moderate (Grade 2), severe (Grade 3), life-threatening (Grade 4), or death due to the AE (Grade 5). Cornea and retina AEs were defined by Standardized Medical Dictionary for Regulatory Activities Queries (SMQs) of corneal disorders and retinal disorders (broad).	From first dose of study drug to 28 days after last dose of study drug. Actual median (min, max) duration of treatment emergent period was 29 (4.1, 157) weeks in the bemarituzumab + mFOLFOX6 group and 28 (4.3, 133) weeks in the placebo + mFOLFOX6 group.