Phase 3 Study of BGJ398 (Oral Infigratinib) in First Line Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations

NCT03773302 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: QBGJ398-3012018-004004-19
• Study Type: interventional
• Target: 48
• Locations: 15 countries
• Sites: 116

Brief Summary

Infigratinib is an oral drug which selectively binds to fibroblast growth factor receptor (FGFR) 2 and is being developed to treat participants with FGFR2 mutated cholangiocarcinoma. The purpose of the study is to evaluate the efficacy and safety of the investigational agent oral infigratinib vs standard of care chemotherapy (gemcitabine plus cisplatin) in first-line treatment of participants with unresectable locally advanced or metastatic cholangiocarcinoma with FGFR2 fusion/rearrangement. Subjects will be randomized 2:1 to receive infigratinib or gemcitabine plus cisplatin.

Conditions

Advanced Cholangiocarcinoma; FGFR2 Gene Mutation

Keywords

cholangiocarcinoma; unresectable cholangiocarcinoma; metastatic cholangiocarcinoma; fibroblast growth factor receptor inhibitor; FGFR2; FGFR2 gene fusions/translocations; BGJ398

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (Central Imaging Assessment)

  Defined as the time from randomization until date of disease progression by blinded independent central imaging assessment (Response Evaluation Criteria in Solid Tumors \[RECIST\] v. 1.1) or death, whichever occurs first.

  From the time of randomization to end of treatment due to confirmed disease progression or death. Note: PFS is an event driven endpoint. Subjects without confirmed disease progression at the end of study were censored at their last valid tumor assessment.

Secondary Outcomes (8)

• Overall Survival (OS) in Participants Treated With Infigratinib Versus Gemcitabine With Cisplatin

  From the time of randomization to time of death. Note: OS is an event driven endpoint. Subjects who had not died (no record of death) or were lost to follow-up were censored at the date of last known to be alive.

• Investigator Assessed Progression Free Survival in Participants Treated With Infigratinib Compared to Gemcitabine and Cisplatin

  From the time of randomization to end of treatment due to confirmed disease progression or death. Note: PFS is an event driven endpoint. Subjects without confirmed disease progression at the end of study were censored at their last valid tumor assessment.

• Overall Response Rate (ORR) Determined by Blinded Independent Central (BICR) and Investigator Assessment

  From the time of randomization to end of study treatment (an average of approx.6.5 months [max: 23 months] for the infigratinib arm and approx. 4 months [max: 11-13 months] for the gemcitabine + cisplatin arm up to the time of termination of the study).

• Best Overall Response (BOR) Determined by Blinded Independent Central Assessment and the Investigator.

  From the time of randomization to end of study treatment (an average of approx.6.5 months [max: 23 months] for the infigratinib arm and approx. 4 months [max: 11-13 months] for the gemcitabine + cisplatin arm up to the time of termination of the study).

• Duration of Response (DOR) Determined by Blinded Independent Central Assessment and the Investigator.

  From the time of randomization to end of study treatment (an average of approx.6.5 months [max: 23 months] for the infigratinib arm and approx. 4 months [max: 11-13 months] for the gemcitabine + cisplatin arm up to the time of termination of the study).

Study Arms (2)

Infigratinib (BGJ398) 125 mg

EXPERIMENTAL

Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off.

Drug: BGJ398

Gemcitabine + Cisplatin

ACTIVE COMPARATOR

Participants who experience disease progression while receiving gemcitabine + cisplatin will be allowed to cross over and receive infigratinib if certain criteria are met.

Drug: Gemcitabine; Drug: Cisplatin

Interventions

BGJ398 DRUG

Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off.

Also known as: Infigratinib

Infigratinib (BGJ398) 125 mg

Gemcitabine DRUG

Gemcitabine 1000 mg/m2 IV D1 and D8 for a 21-day cycle. Participants who experience disease progression while receiving gemcitabine + cisplatin will be allowed to cross over and receive infigratinib.

Gemcitabine + Cisplatin

Cisplatin DRUG

Cisplatin 25 mg/m2 IV D1 and D8 for a 21-day cycle. Participants who experience disease progression while receiving gemcitabine + cisplatin will be allowed to cross over and receive infigratinib.

Gemcitabine + Cisplatin

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed unresectable locally advanced or metastatic cholangiocarcinoma. Participants with gallbladder cancer or ampulla of Vater carcinoma are not eligible
• Have written documentation of local laboratory or central laboratory determination of a known or likely activating FGFR2 fusion/rearrangement from a sample collected before randomization
• Have an archival tumor tissue sample available with sufficient tumor content for FGFR2 fusion/rearrangement molecular testing by the central laboratory. However, if an archival tumor tissue sample is not available, or does not meet requirements for central testing a newly obtained (before randomization) tumor biopsy may be submitted instead. If a prestudy written documentation of FGFR2 fusion/rearrangement in tumor tissue is available from the central laboratory, an additional tumor sample does not need to be submitted.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Are able to swallow and retain oral medication
• Are willingness to avoid pregnancy or father children

You may not qualify if:

• Received treatment with any systemic anti-cancer therapy for unresectable locally advanced or metastatic cholangiocarcinoma, with following exceptions
• Prior neoadjuvant or adjuvant therapy is permitted if completed \> 6 months after the last dose of neoadjuvant or adjuvant therapy.
• One cycle of gemcitabine-based chemotherapy for locally advanced or metastatic cholangiocarcinoma is permitted before randomization
• History of a liver transplant
• Received previously or currently is receiving treatment with a mitogen activated protein kinase kinase (MEK) or selective FGFR inhibitor
• Have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib (such as, ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).
• Current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc.
• History and/or current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, myocardium, vascular system and lung with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, and asymptomatic coronary calcification
• Current evidence of corneal or retinal disorder/keratopathy
• Receiving and continued treatment or are planning to receive agents or consuming foods that are known moderate or strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration
• Clinically significant or uncontrolled cardiac disease
• Recent (≤ 3 months prior to first dose of study drug) transient ischemic attack or stroke
• Severe hearing loss
• Severe neuropathy
• History of another primary malignancy within 3 years except adequately treated in-situ carcinoma of the cervix or non-melanoma skin cancer or other curatively treated malignancy that is not expected to require treatment

Sponsors & Collaborators

• QED Therapeutics, a BridgeBio company: lead
• Helsinn Healthcare SA: collaborator

Study Sites (116)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

University of Arizona

Tucson, Arizona, 85724, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

St. Joseph Heritage Healthcare

Fullerton, California, 92835, United States

Location

USC Norris Cancer Center

Los Angeles, California, 90033, United States

Location

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

Florida Hospital Medical Group

Orlando, Florida, 32804, United States

Location

UF Health Cancer Center at Orlando Health

Orlando, Florida, 32806, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

University Medical Center - New Orleans

New Orleans, Louisiana, 70112, United States

Location

Frederick Regional Healthcare Systems/James M. Stockman Cancer Institute

Frederick, Maryland, 21702, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Barbara Ann Karmanos Cancer Institute - Lawrence and Idell Weisberg Cancer Treatment Center

Detroit, Michigan, 48201, United States

Location

Cancer and Hematology Centers of Western Michigan

Grand Rapids, Michigan, 49503, United States

Location

William Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Levine Cancer Institute - Charlotte

Charlotte, North Carolina, 28204, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43202, United States

Location

Charleston Oncology

Charleston, South Carolina, 29414, United States

Location

Parkland Health and Hospital System

Dallas, Texas, 75343, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Baylor College of Medicine

Houston, Texas, 77096, United States

Location

Chris O'Brien Lifehouse Hospital

Camperdown, New South Wales, Australia

Location

Blacktown Hospital

Darlinghurst, New South Wales, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Location

Monash Medical Centre

Bentleigh East, Victoria, Australia

Location

Peninsula & South Eastern Haematology and Oncology Group

Frankston, Victoria, Australia

Location

St John of God Hospital Subiaco

Subiaco, Western Australia, Australia

Location

Cliniques Universitaires Saint-Luc

Brussels, Brussels Capital, 1200, Belgium

Location

Grand Hopital de Charleroi

Charleroi, 6000, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

Location

Cross Cancer Institute

Edmonton, Alberta, Canada

Location

Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

St. Josephs Health Centre

Toronto, Ontario, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Peking University People's Hospital

Beijing, 100033, China

Location

Beijing Cancer Hospital

Beijing, 100142, China

Location

Peking University Third Hospital

Beijing, 100191, China

Location

Hunan Cancer Hospital

Changsha, 410006, China

Location

Guangzhou First People's Hospital

Guangzhou, 510080, China

Location

Hubei Cancer Hospital

Hubei, 430079, China

Location

Liaoning Cancer Hospital & Institute

Shenyang, 110042, China

Location

The First Affiliated Hospital, Sun Yat-sen University

Zhongshan, 510060, China

Location

Hopital Henri Mondor

Créteil, Val-de-Marne, 94000, France

Location

CHRU Dijon

Dijon, 21000, France

Location

Centre Georges-Francois Leclerc

Dijon, 21079, France

Location

Hopital Claude Huriez Rue Michel Polonovski (CHRU) Lille

Lille, 59000, France

Location

Groupement Hospitalier Edouard Herriot

Lyon, 69437, France

Location

Hopital Nord Franche-Comte

Montbéliard, 25200, France

Location

Groupe Hospitalier Archet I Et II

Nice, 06202, France

Location

Hopital Cochin

Paris, 75014, France

Location

Hôpital Saint Antoine

Paris, 75571, France

Location

L'Institut Mutualiste Montsouris

Paris, 75674, France

Location

Universitätsklinikum Tübingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Klinikum rechts der Isar der Technischen Universität München

München, Bavaria, 81675, Germany

Location

Klinikum Dortmund gGmbH

Dortmund, 44137, Germany

Location

University Clinic Heidelberg

Heidelberg, 69120, Germany

Location

Azienda Socio Sanitaria Territoriale di Cremona (ASST)

Cremona, 26100, Italy

Location

Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST

Meldola, 47014, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Istituto Oncologico Veneto - I.R.C.C.S.

Padua, 35128, Italy

Location

Policlinico Universitario Campus Biomedico Di Roma

Roma, 00128, Italy

Location

Hospital Beatriz Angelo

Loures, Lisbon District, 2674-514, Portugal

Location

Hospital Garcia de Orta

Almada, 2801-951, Portugal

Location

Centro Hospitalar E Universitário de Coimbra EPE

Coimbra, 3000-075, Portugal

Location

Instituto Português de Oncologia Francisco Gentil Centro Regional de Oncologia de Coimbra EPE

Coimbra, 3000-075, Portugal

Location

Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.

Lisbon, 1099-023, Portugal

Location

Centro Hospitalar Lisboa Norte, E.P.E. - Hospital de Santa Maria

Lisbon, 1649-035, Portugal

Location

Hospital CUF Descobertas

Lisbon, 1998-018, Portugal

Location

Centro Hospitalar do Porto - Hospital de Santo António

Porto, 4099-001, Portugal

Location

Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS

Porto, 4200-072, Portugal

Location

Centro Hospitalar de São João, E.P.E.

Porto, 4200-319, Portugal

Location

Hospital Oncologico, Puerto Rico Medical Center

Rio Piedras, 00935, Puerto Rico

Location

Pusan National University Hospital

Pusan, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, South Korea

Location

SMG - SNU Boramae Medical Center

Seoul, 07061, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, South Korea

Location

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, South Korea

Location

Ajou University Hospital

Suwon, South Korea

Location

Hospital Universitario Virgen Macarena

Seville, Andalusia, 41009, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Aragon, 50009, Spain

Location

Complejo Asistencial Universitario de Salamanca - Hospital Clinico

Salamanca, Castille and León, 37007, Spain

Location

Hospital Universitario Germans Trias i Pujol

Badalona, Catalonia, 08916, Spain

Location

Instituto Catalan de Oncologio ICO I'Hospitalet

Barcelona, Catalonia, 08907, Spain

Location

Hospital Universitario Vall d'Hebrón - PPDS

Barcelona, 08035, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario HM Sanchinarro - CIOCC

Madrid, 28050, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

National Cheng Kung University Hospital

Tainan, Tainan, 704, Taiwan

Location

National Taiwan University Hospital - YunLin Branch

Huwei, 632, Taiwan

Location

Chang Gung Memorial Hospital - Kaohsiung

Kaohsiung City, 833, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Chi Mei Hospital, Liouying

Tainan, 73657, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Chang Gung Memorial Hospital, Linkou

Taoyuan, 333, Taiwan

Location

Songklanagarind Hospital, Prince of Songkla University

Hat Yai, Changwat Songkhla, 90110, Thailand

Location

Chulalongkorn University

Bangkok, 10330, Thailand

Location

Ramathibodi Hospital Mahidol University

Bangkok, Thailand

Location

Maharaj Nakorn Chiang Mai Chiang Mai University

Chiang Mai, 50200, Thailand

Location

Srinagarind Hospital

Khon Kaen, Thailand

Location

Naresuan University

Phitsanulok, Thailand

Location

Nottingham City Hospital

Nottingham, Nottinghamshire, NG5 1PB, United Kingdom

Location

Royal Marsden Hospital

Sutton, Surrey, SM2 5PT, United Kingdom

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Bebington, Wirral, CH63 4JY, United Kingdom

Location

Guys Hospital

London, SE1 9RT, United Kingdom

Location

The Christie NHS Foundation Trust - PPDS

Manchester, M20 4BX, United Kingdom

Location

Related Publications (1)

• Makawita S, K Abou-Alfa G, Roychowdhury S, Sadeghi S, Borbath I, Goyal L, Cohn A, Lamarca A, Oh DY, Macarulla T, T Shroff R, Howland M, Li A, Cho T, Pande A, Javle M. Infigratinib in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF 301 trial. Future Oncol. 2020 Oct;16(30):2375-2384. doi: 10.2217/fon-2020-0299. Epub 2020 Jun 25.

  PMID: 32580579 DERIVED

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

infigratinib; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Acting Chief Medical Officer
• Organization: QED Therapeutics, Inc.

PROOF301.ct@qedtx.com

1-877-280-5655

Study Officials

• Clinical Development

  QED Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multicenter, Open Label, 2:1 Randomized, Controlled Phase 3

Study Record Dates

• First Submitted: December 10, 2018
• First Posted: December 12, 2018
• Study Start: December 27, 2019
• Primary Completion: March 2, 2023
• Study Completion: March 2, 2023
• Last Updated: May 8, 2024
• Results First Posted: May 8, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (4); IT (6); US (25); PT (10); BE (3); CN (8); TH (6); GB (5); AU (6); CA (4); PR (1); FR (10); ES (12); TW (8); KR (8)