MedPath

A Study Evaluating Bemarituzumab in Solid Tumors With Fibroblast Growth Factor Receptor 2b (FGFR2b) Overexpression

Phase 1
Active, not recruiting
Conditions
Solid Tumors
Interventions
Registration Number
NCT05325866
Lead Sponsor
Amgen
Brief Summary

The primary objectives of this study are to observe the safety and tolerability of bemarituzumab and to evaluate preliminary antitumor activity.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
260
Inclusion Criteria
  1. Age ≥ 18 years (or legal adult age within country, whichever is older) at the time that the Informed Consent Form (ICF) is signed

  2. Histologically or cytologically confirmed cancer of one of the following types, refractory to or relapsed after at least 1 prior standard therapeutic regimen in the advanced/metastatic setting, as specified below. If no standard of care therapies exist for the participant, or the participant cannot tolerate or refuses standard of care anticancer therapy, the participant may be allowed to participate on the study after discussion between the investigator and Amgen medical monitor. Participants who have not received all approved or standard treatments for their cancer must be informed that these alternatives to receiving bemarituzumab are available prior to consenting to participate in the trial.

    • head and neck squamous cell carcinoma: ≥ 1 line of therapy
    • triple-negative breast cancer: ≥ 2 lines of therapy
    • Intrahepatic cholangiocarcinoma ≥ 1 line of therapy
    • lung adenocarcinoma: at least platinum-based chemotherapy, checkpoint inhibitor, and targeted therapy
    • platinum resistant ovarian epithelial cell carcinoma, including fallopian tube cancers and primary peritoneal cancers, defined as progression during or within 6 months of a platinum containing regimen: ≥ 1 line of therapy
    • endometrial adenocarcinoma: ≥ 1 line of therapy
    • cervical carcinoma: ≥ 1 line of therapy
    • other solid tumors: ≥ 1 line of therapy
  3. Disease that is unresectable, locally advanced, or metastatic (not amenable to curative therapy)

  4. Tumor overexpresses FGFR2b as determined by centrally performed immunohistochemistry (IHC) testing

  5. Measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1

  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

  7. Adequate organ function as determined per protocol.

Exclusion Criteria
  1. Untreated or symptomatic central nervous system (CNS) metastases or leptomeningeal disease.
  2. Other solid tumor cohort excludes primary tumors of the CNS, squamous non-small cell lung cancer, gastric adenocarcinoma, and gastroesophageal junction adenocarcinoma
  3. Impaired cardiac function or clinically significant cardiac disease including: unstable angina within 6 months prior to first dose of study treatment, acute myocardial infarction ≥ 6 months prior to first dose of study treatment, New York Heart Association (NYHA) class II-IV congestive heart failure, uncontrolled hypertension (defined as an average systolic blood pressure ≥ 160 mmHg or diastolic ≥ 100 mmHg despite optimal treatment, uncontrolled cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin, active coronary artery disease or corrected QT interval QTc ≥ 470
  4. History of systemic disease or ophthalmologic disorders requiring chronic use of ophthalmic steroids
  5. Evidence of any ongoing ophthalmologic abnormalities or symptoms that are acute (within 4 weeks) or actively progressing
  6. Unwillingness to avoid use of contact lenses during study treatment and for at least 100 days after the end of treatment
  7. Recent (within 6 months) corneal surgery or ophthalmic laser treatment or recent (within 6 months) history of, or evidence of, corneal defects, corneal ulcerations, keratitis, or keratoconus, or other known abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer prior/concomitant therapy
  8. Prior treatment with any investigational selective inhibitor of the fibroblast growth factor (FGF)/FGF receptor pathway (unless approved standard of care for tumor indication).

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Part 1: Monotherapy Dose ExplorationBemarituzumabParticipants across multiple primary epithelial solid tumors with centrally determined FGFR2b overexpression and relapsed/refractory unresectable and/or metastatic disease will receive 1 of 2 dose regimens of bemarituzumab to determine recommended Phase 2 dose.
Part 2: Monotherapy Dose ExpansionBemarituzumabParticipants across multiple primary epithelial solid tumors with centrally determined FGFR2b overexpression and relapsed/refractory unresectable and/or metastatic disease will receive the dose of bemarituzumab identified as the recommended Phase 2 dose during Part 1.
Primary Outcome Measures
NameTimeMethod
Part 1: Number of Participants Who Experience a Dose Limiting Toxicity (DLT)Day 1 to Day 28
Part 1: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)Day 1 to 28 days after last dose (a maximum of 2 years)

Adverse events (AEs) are defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are any event that occurs after the participant has received study treatment. Any clinically significant changes in vital signs, visual acuity, and clinical laboratory tests that occur after study treatment administration will be recorded as TEAEs.

Part 1: Number of Participants Who Experience a Treatment-related Adverse EventDay 1 to 28 days after last dose (a maximum of 2 years)
Part 2: Objective Response (OR) RateUp to approximately 2 years

OR = complete response (CR) + partial response (PR), measured by computed tomography (CT) or magnetic resonance imaging (MRI) as determined by investigator per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

Secondary Outcome Measures
NameTimeMethod
Part 1: OR RateUp to approximately 2 years

OR = CR + PR, measured by CT or MRI as determined by investigator per RECIST v1.1.

Parts 1 and 2: Disease Control (DC) RateUp to approximately 2 years

DC = CR, PR, or stable disease (SD).

Parts 1 and 2: Duration of Response (DOR)Up to approximately 2 years

DOR, defined as the time from first documentation of OR (as determined by investigator per RECIST v1.1) until the first documentation of disease progression or death due to any cause, whichever occurs first. Only participants who have achieved OR will be evaluated for DOR. DOR will be censored at the last evaluable post-baseline tumor assessment prior to subsequent anticancer therapy.

Parts 1 and 2: Time to ResponseUp to approximately 2 years
Parts 1 and 2: Progression-free Survival (PFS)Up to approximately 2 years

PFS, defined as time from first dose of investigational product until the first documentation of radiologic disease progression or death due to any cause. PFS will be censored at the last evaluable post-baseline tumor assessment prior to subsequent therapy. Progression will be based on RECIST v1.1 (derived utilizing investigator tumor assessments).

Parts 1 and 2: Overall Survival (OS)Up to approximately 2 years

OS, defined as time from first dose of investigational product until death from any cause. Participants still alive will be censored at the date last known to be alive.

Part 2: Number of Participants Who Experience a TEAEDay 1 to 28 days after last dose (a maximum of 2 years)

AEs are defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are any event that occurs after the participant has received study treatment. Any clinically significant changes in vital signs, visual acuity, and clinical laboratory tests that occur after study treatment administration will be recorded as TEAEs.

Part 2: Number of Participants Who Experience a Treatment-related AEDay 1 to 28 days after last dose (a maximum of 2 years)
Parts 1 and 2: Area Under the Concentration Time Curve (AUC) of BemarituzumabDay 1 to 28 days after last dose (a maximum of 2 years)
Parts 1 and 2: Maximum Observed Serum Concentration (Cmax) of BemarituzumabDay 1 to 28 days after last dose (a maximum of 2 years)
Parts 1 and 2: Observed Concentration at the End of a Dose Interval (Ctrough) of BemarituzumabDay 1 to 28 days after last dose (a maximum of 2 years)

Trial Locations

Locations (115)

Landeskrankenhaus Salzburg

🇦🇹

Salzburg, Austria

Gustave Roussy

🇫🇷

Villejuif, France

Kantonsspital Graubuenden

🇨🇭

Chur, Switzerland

Universitair Ziekenhuis Antwerpen

🇧🇪

Edegem, Belgium

Oncoclinicas Rio de Janeiro S A

🇧🇷

Rio de Janeiro, Brazil

Institut Paoli Calmettes

🇫🇷

Marseille Cedex 09, France

Sotiria General Hospital

🇬🇷

Athens, Greece

European Interbalkan Medical Center

🇬🇷

Thessaloniki, Greece

Semmelweis Egyetem

🇭🇺

Budapest, Hungary

Orszagos Onkologiai Intezet

🇭🇺

Budapest, Hungary

Medizinische Universitaet Graz

🇦🇹

Graz, Austria

City of Hope National Medical Center

🇺🇸

Duarte, California, United States

University of California Irvine

🇺🇸

Orange, California, United States

Rocky Mountain Cancer Centers

🇺🇸

Aurora, Colorado, United States

Community Health Network MD Anderson Cancer Center - North

🇺🇸

Indianapolis, Indiana, United States

Henry Ford Hospital

🇺🇸

Detroit, Michigan, United States

United States Oncology Regulatory Affairs Corporate Office

🇺🇸

Nashville, Tennessee, United States

Texas Oncology - Dallas Fort Worth

🇺🇸

Dallas, Texas, United States

University of Texas MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

US Oncology Research Investigational Products Center

🇺🇸

Irving, Texas, United States

Texas Oncology Northeast Texas

🇺🇸

Tyler, Texas, United States

Instituto Alexander Fleming

🇦🇷

Capital Federal, Buenos Aires, Argentina

Hospital Aleman

🇦🇷

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

Fundacion Cenit Para La Investigacion

🇦🇷

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

Hospital Italiano de La Plata

🇦🇷

La Plata, Buenos Aires, Argentina

Sociedad de Beneficencia Hospital Italiano

🇦🇷

Cordoba, Córdoba, Argentina

Fundacion Medica de Rio Negro y Neuquen

🇦🇷

Cipolletti, Río Negro, Argentina

Centro Oncologico Korben

🇦🇷

Buenos Aires, Argentina

Liverpool Hospital

🇦🇺

Liverpool, New South Wales, Australia

Prince of Wales Hospital

🇦🇺

Randwick, New South Wales, Australia

Wollongong Hospital

🇦🇺

Wollongong, New South Wales, Australia

Toowoomba Hospital

🇦🇺

Toowoomba, Queensland, Australia

Cabrini Hospital

🇦🇺

Malvern, Victoria, Australia

St John of God Murdoch Hospital

🇦🇺

Murdoch, Western Australia, Australia

Universite Catholique de Louvain Cliniques Universitaires Saint Luc

🇧🇪

Bruxelles, Belgium

Grand Hopital de Charleroi - Site des Viviers

🇧🇪

Charleroi, Belgium

Universitair Ziekenhuis Gent

🇧🇪

Gent, Belgium

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

🇧🇪

Leuven, Belgium

Hospital das Clinicas da Ufmg

🇧🇷

Belo Horizonte, Minas Gerais, Brazil

Centro de Oncologia Mackenzie

🇧🇷

Curitiba, Paraná, Brazil

Associacao Hospitalar Moinhos de Vento

🇧🇷

Porto Alegre, Rio Grande Do Sul, Brazil

Instituto do Cancer Arnaldo Vieira de Carvalho

🇧🇷

Sao Paulo, São Paulo, Brazil

Beneficencia Portuguesa de Sao Paulo - Bp

🇧🇷

Sao Paulo, São Paulo, Brazil

Oncologia Rede D Or

🇧🇷

Sao Paulo, São Paulo, Brazil

Multiprofile Hospital for Active Treatment Central Onco Hospital OOD

🇧🇬

Plovdiv, Bulgaria

Complex Oncology Center Plovdiv EOOD

🇧🇬

Plovdiv, Bulgaria

Military Medical Academy Multiprofile Hospital for Active Treatment - Sofia

🇧🇬

Sofia, Bulgaria

Cross Cancer Institute

🇨🇦

Edmonton, Alberta, Canada

The Ottawa Hospital Cancer Centre

🇨🇦

Ottawa, Ontario, Canada

Princess Margaret Cancer Centre

🇨🇦

Toronto, Ontario, Canada

Masarykuv onkologicky ustav

🇨🇿

Brno, Czechia

Fakultni nemocnice Hradec Kralove

🇨🇿

Hradec Kralove, Czechia

Fakultni nemocnice Olomouc

🇨🇿

Olomouc, Czechia

Fakultni nemocnice Kralovske Vinohrady

🇨🇿

Praha 10, Czechia

Rigshospitalet

🇩🇰

Kobenhavn O, Denmark

Docrates Syopasairaala

🇫🇮

Helsinki, Finland

Tampere University Hospital

🇫🇮

Tampere, Finland

Institut de Cancerologie de l Ouest Rene Gauducheau

🇫🇷

Angers Cedex 02, France

Centre Hospitalier Regional Universitaire de Besancon - Hopital Jean Minjoz

🇫🇷

Besancon, France

Centre Oscar Lambret

🇫🇷

Lille Cedex, France

Institut regional du Cancer Montpellier

🇫🇷

Montpellier Cedex 5, France

Hopital Lyon sud

🇫🇷

Pierre-Benite, France

Institut Universitaire du Cancer Toulouse Oncopole

🇫🇷

Toulouse cedex 9, France

Alexandra Hospital

🇬🇷

Athens, Greece

Metropolitan General

🇬🇷

Athens, Greece

University Hospital of Heraklion

🇬🇷

Heraklion - Crete, Greece

Szabolcs-Szatmar-Bereg Varmegyei Oktatokorhaz Nyiregyhazi Josa Andras Tagkorhaz

🇭🇺

Nyiregyhaza, Hungary

Jasz-Nagykun-Szolnok Varmegyei Hetenyi Geza Korhaz-Rendelointezet

🇭🇺

Szolnok, Hungary

Rambam Medical Center

🇮🇱

Haifa, Israel

Hadassah Ein-Kerem Medical Center

🇮🇱

Jerusalem, Israel

Rabin Medical Center

🇮🇱

Petah Tikva, Israel

Sheba Medical Center

🇮🇱

Ramat Gan, Israel

Tel-Aviv Sourasky Medical Center

🇮🇱

Tel Aviv, Israel

Istituto di Candiolo Fondazione del Piemonte per l Oncologia IRCCS

🇮🇹

Candiolo TO, Italy

Azienda Ospedaliero Universitaria Ospedali Riuniti di Foggia

🇮🇹

Foggia, Italy

Azienda Unita Locale Socio Sanitaria 3 Presidio Ospedaliero di Mirano

🇮🇹

Mirano, Italy

Ospedale del Mare

🇮🇹

Napoli, Italy

Azienda Ospedaliero Universitaria Pisana

🇮🇹

Pisa, Italy

Azienda Ospedaliera Policlinico Umberto I

🇮🇹

Roma, Italy

Aichi Cancer Center

🇯🇵

Nagoya-shi, Aichi, Japan

National Cancer Center Hospital East

🇯🇵

Kashiwa-shi, Chiba, Japan

Kindai University Hospital

🇯🇵

Osakasayama-shi, Osaka, Japan

National Cancer Center Hospital

🇯🇵

Chuo-ku, Tokyo, Japan

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

🇯🇵

Koto-ku, Tokyo, Japan

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Severance Hospital Yonsei University Health System

🇰🇷

Seoul, Korea, Republic of

Samsung Medical Center

🇰🇷

Seoul, Korea, Republic of

Asan Medical Center

🇰🇷

Seoul, Korea, Republic of

Investigacion Onco Farmacéutica S de RL de CV

🇲🇽

La Paz, Baja California Sur, Mexico

Centro de Infusion e Investigacion Oncologia de Saltillo

🇲🇽

Saltillo, Coahuila, Mexico

Investigacion Biomedica para el Desarrollo de Farmacos

🇲🇽

Ciudad de Mexico, Distrito Federal, Mexico

Health Pharma Professional Research SA de CV

🇲🇽

Mexico City, Distrito Federal, Mexico

Christus Muguerza Clinica Vidriera

🇲🇽

Monterrey, Nuevo León, Mexico

Universitair Medisch Centrum Groningen

🇳🇱

Groningen, Netherlands

Radboud Universitair Medisch Centrum

🇳🇱

Nijmegen, Netherlands

Pratia Mcm Krakow

🇵🇱

Krakow, Poland

Instytut Centrum Zdrowia Matki Polki

🇵🇱

Lodz, Poland

Ars Medical Spzoo

🇵🇱

Pila, Poland

Mazowiecki Szpital Wojewodzki im Sw Jana Pawla II w Siedlcach spzoo

🇵🇱

Siedlce, Poland

Centrum Medyczne Pratia Poznan

🇵🇱

Skorzewo, Poland

Unidade Local de Saude de Lisboa Ocidental, EPE - Hospital Sao Francisco Xavier

🇵🇹

Lisboa, Portugal

Hospital da Luz, SA

🇵🇹

Lisboa, Portugal

Unidade Local de Saude de Santa Maria, EPE - Hospital de Santa Maria

🇵🇹

Lisboa, Portugal

Institutul Oncologic Prof Dr Ion Chiricuta Cluj-Napoca

🇷🇴

Cluj Napoca, Romania

Centrul de Oncologie Sf Nectarie SRL

🇷🇴

Craiova, Romania

Institutul Regional de Oncologie Iasi

🇷🇴

Iasi, Romania

SC Oncomed SRL

🇷🇴

Timisoara, Romania

Hospital Clinico Universitario Virgen de la Victoria

🇪🇸

Malaga, Andalucía, Spain

Hospital Quironsalud Barcelona

🇪🇸

Barcelona, Cataluña, Spain

Hospital Universitari Vall d Hebron

🇪🇸

Barcelona, Cataluña, Spain

Hospital Clinico Universitario de Santiago

🇪🇸

Santiago de Compostela, Galicia, Spain

Hospital General Universitario Gregorio Maranon

🇪🇸

Madrid, Spain

Hopitaux Universitaires de Geneve

🇨🇭

Geneve 14, Switzerland

Christie Hospital

🇬🇧

Manchester, United Kingdom

Weston Park Hospital

🇬🇧

Sheffield, United Kingdom

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