Clinical trial NCT06064877: A Study of Ficlatuzumab in Combination With Cetuximab in Participants With Recurrent or Metastatic (R/M) HPV Negative Head and Neck Squamous Cell Carcinoma
Official title: A Multicenter, Randomized, Double Blind, Placebo - Controlled, Phase 3 Study of Ficlatuzumab in Combination With Cetuximab in Participants With Recurrent or Metastatic (R/M) HPV -Negative Head and Neck Squamous Cell Carcinoma. (FIERCE-HN)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Metastatic Head-and-neck Squamous-cell Carcinoma
Recurrent Head and Neck Squamous Cell Carcinoma
Keywords: Recurrent
Metastatic
HPV-negative
Head and Neck
Squamous Cell Carcinoma
Lead sponsor: AVEO Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2023-10-03
Enrollment: 410
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the efficacy and safety of ficlatuzumab plus cetuximab compared to placebo plus cetuximab in participants with recurrent/metastatic (R/M) HPV-negative Head and Neck Cancer.

The primary hypothesis is that ficlatuzumab combined with cetuximab is superior to cetuximab alone in terms of progression-free survival and/or overall survival.

Detailed description: This multicenter, randomized, double-blind, placebo-controlled Phase 3 study is designed to compare the efficacy and safety of two dose levels of ficlatuzumab combined with cetuximab (Arm 1 or Arm 2) to a control arm of placebo plus cetuximab (Arm 3) in participants with R/M human papilloma virus (HPV)-negative HNSCC. Eligible participants must have failed prior therapy with an anti-PD-1 \[programmed cell death protein 1\] or PD-L1 \[programmed death ligand 1\] immune checkpoint inhibitor (ICI) and with platinum-based chemotherapy, administered in combination or sequentially. Failure of prior treatment may be due to progression of disease or intolerance to treatment. It is anticipated that the study will enroll approximately 410 participants across 3 arms.

Eligibility criteria: Inclusion Criteria:

* Male or female and ≥ 18 years of age
* Histologically and/or cytologically confirmed primary diagnosis of R/M HNSCC
* Participants with oropharyngeal cancer will be required to have proof of p16 negative status submitted on the basis of a pathology report
* At least 1 measurable lesion by contrast CT or MRI scan according to RECIST v.1.1. Such lesions must not have been previously irradiated; if the measurable lesion(s) has been irradiated, clear progression must be documented
* Participants must have failed prior therapy with an anti-PD-1/PD-L1 ICI and with platinum-based chemotherapy administered in combination or sequentially, in either the locally advanced or R/M setting. Failure of prior treatment may be due to progression of disease or intolerance to treatment
* Patient's tumor must be considered inoperable and incurable
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with a life expectancy of at least 12 weeks
* For women of childbearing potential (WOCBP), documentation of negative serum pregnancy test within 30 days of randomization
* For WOCBP and male participants whose sexual partners are of childbearing potential, agreement to use an effective method of contraception during the study and for at least 5 months after the last dose of study treatment. Birth control methods which may be considered highly effective include methods that achieve a failure rate of less than 1% per year when used consistently and correctly.
* Ability to give written informed consent and comply with protocol requirements
* Patients with feeding tubes are eligible for the study.
* Archived tissue sample must be submitted to the Sponsor-designated laboratory within 60 days of randomization for c-Met analysis (if a tissue sample is not available, a fresh biopsy may be required prior to enrollment)

Exclusion Criteria:

* Participants who have received \> 2 prior lines of anticancer therapy or prior treatment with cetuximab/alternative EGFR inhibitors for the treatment of R/M HNSCC
* History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational agent or cetuximab
* Known or suspected untreated and uncontrolled brain metastases or leptomeningeal carcinomatosis Note: Participants with locally treated brain metastases are eligible provided 2 weeks have elapsed since local therapy. Participants are allowed to continue steroid taper during the start of study treatment.
* Prior treatment with any other investigational drug or biologic agent or radiation therapy before a washout has been completed (must be completed prior to randomization):

  1. 2 weeks (14 days) or 5 half-lives, whichever is shorter, for chemotherapeutic agents, small molecules, and checkpoint inhibitors
  2. 3 weeks (21 days) or 5 half-lives, whichever is shorter, for antibody-drug conjugates
  3. 4 weeks (28 days) for cell therapies
  4. 2 weeks (14 days) for radiation therapy
* Any unresolved and significant toxicity (National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] version 5.0) Grade \> 2 from previous anticancer therapy (including radiation therapy), other than alopecia
* Significant cardiovascular disease, including: Cardiac failure New York Heart Association class III or IV; Myocardial infarction, severe or unstable angina within 6 months prior to randomization; History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation)
* Any other medical condition or psychiatric condition that, in the opinion of the Investigator, might interfere with the participant's involvement in the study or interfere with the interpretation of study results
* History of prior malignancy within 2 years prior to randomization (except for adequately treated non-melanoma skin cancer, carcinoma in situ of the breast or cervix, superficial bladder cancer, or early-stage prostate cancer, without evidence of recurrence; participants may or may not be on maintenance therapy)
* Participants who are positive for HBV or HCV with indication of acute or chronic hepatitis (as defined in protocol)
* Radiographic evidence (historical or at screening) of interstitial lung disease or idiopathic pulmonary fibrosis
* Female participants who are pregnant or breastfeeding

A full list of inclusion and exclusion criteria can be found in the protocol.

Primary outcomes:
measure: To compare the efficacy by overall survival of ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC)
timeFrame: From Randomization until death from any cause (Approximately 44 months)
Secondary outcomes:
measure: To evaluate progression-free survival (PFS) for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC
timeFrame: From Randomization until disease progression or death (Approximately 44 months)
measure: To evaluate additional objective response rate for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC
timeFrame: From Cycle 1 Day 1 until last response assessment (response assessments are every 8 weeks for the first year, every 12 weeks for years 2 and 3 and then every 6 months)
measure: To evaluate disease control rate (DCR) for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC
timeFrame: From Cycle 1 Day 1 until last response assessment (response assessments are every 8 weeks for the first year, every 12 weeks for years 2 and 3 and then every 6 months)
measure: To evaluate duration of response (DOR) for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC
timeFrame: From Cycle 1 Day 1 until last response assessment (response assessments are every 8 weeks for the first year, every 12 weeks for years 2 and 3 and then every 6 months)
measure: To compare the safety and tolerability of ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC
timeFrame: From Screening until 30 days after last dose
measure: To evaluate the pharmacokinetics (PK) of ficlatuzumab
timeFrame: From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months)
measure: To assess the immunogenicity of ficlatuzumab via antidrug antibodies (ADAs)
timeFrame: From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months)
measure: To assess the immunogenicity of ficlatuzumab via neutralizing antibodies (nAB)
timeFrame: From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months)
measure: To evaluate the quality of life (QOL) of ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC
timeFrame: From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months)
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Tucson
country: United States
facility: The University of Arizona Cancer Center
state: Arizona
city: Westwood
country: United States
facility: University of California Los Angeles
state: California
city: New Haven
country: United States
facility: Yale School of Medicine - Smilow Cancer Hospital
state: Connecticut
city: Washington
country: United States
facility: The George Washington University
state: District of Columbia
city: Orlando
country: United States
facility: AdventHealth Medical Group Oncology & Hematology at Orlando
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Illinois Cancer Center
state: Illinois
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center
state: Louisiana
city: South Portland
country: United States
facility: MaineHealth Institute for Research
state: Maine
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Siteman Cancer Center - Washington University
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Lake Success
country: United States
facility: Northwell Health Cancer Institute
state: New York
city: New York
country: United States
facility: Manhattan Eye, Ear & Throat Hospital
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati - UC Health Barrett Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University, James Cancer Hospital and Solove Research Institute
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburg
country: United States
facility: University of Pittsburgh Medical Center - Hillman Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: Oncology Consultants
state: Texas
city: Richmond
country: United States
facility: VCU Massey Cancer Center
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin - Froedtert Hospital Cancer Center
state: Wisconsin
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
city: Sydney
country: Australia
facility: St. Vincent's Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Murdoch
country: Australia
facility: St. John of God Murdoch Hospital
state: Western Australia
city: Liège
country: Belgium
facility: CHU Liège
city: Namur
country: Belgium
facility: CHU Universite Catholique de Louvain
city: Sint-Niklaas
country: Belgium
facility: Vitaz-Sint-Niklaas Moerland
city: Panagyurishte
country: Bulgaria
facility: University Hospital
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre (Alberta Health Services)
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center - University Health Network
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Centre (MUHC)
state: Quebec
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Brno
country: Czechia
facility: Masaryk Memorial Cancer Institute
city: Olomouc
country: Czechia
facility: Fakultni Nemocnice Olomouc
city: Prague
country: Czechia
facility: Fakultni Nemocnice Kralovske Vinohrady
city: Prague
country: Czechia
facility: Fakultni nemocnice Bulovka
city: Brest
country: France
facility: Clinique Pasteur - Lanroze- Centre Finistérien de Radiothérapie et d'Oncologie
city: Chambray-lès-Tours
country: France
facility: Pôle Santé Léonard de Vinci
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Assistance Publique Hopitaux de Marseille (APHM)-Hôpital La Timone
city: Paris
country: France
facility: Institut Curie
city: Plérin
country: France
facility: Hôpital Privé des Côtes d'Armor
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Charite-Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK) - Medizinische Klinik mit Schwerpunkt Haematologie, Onkologie und Tumorimmunologie
city: Freiburg
country: Germany
facility: UNIVERSITÄTSKLINIKUM FREIBURG, Klinik für Innere Medizin I, Schwerpunkt Hämatologie, Onkologie und Stammzelltransplantation
city: Munich
country: Germany
facility: Ludwig-Maximilians University
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet
city: Győr
country: Hungary
facility: Petz Aladar Country Teaching Hospital
city: Nyíregyháza
country: Hungary
facility: Josa Andras Oktatokorhaz
city: Pécs
country: Hungary
facility: University of Pecs - Oncology
city: Salgótarján
country: Hungary
facility: Szent Lázár Megyei Kórház
city: Bologna
country: Italy
facility: IRCCS Istituto Scienze Neurologiche
city: Firenze
country: Italy
facility: AOU Careggi
city: Milano
country: Italy
facility: IRCCS Istituto Clinico Humanitas - Cancer center
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele Milano
city: Milano
country: Italy
facility: Fondazione IRCCS - Istituto Nazionale Tumori - Oncologia
city: Novara
country: Italy
facility: Azienda Ospedaliera Universitaria Maggiore Della Carita Novara
city: Padua
country: Italy
facility: Istituto Oncologico Veneto
city: Pavia
country: Italy
facility: IRCCS - ICS Maugeri
city: Pavia
country: Italy
facility: Universita degli Studi di Pavia - Fondazione IRCCS Policlinico San Matteo
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Eunpyeong St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. prof. F. Lukaszczyka w Bydgoszczy
city: Gliwice
country: Poland
facility: National Research Institute of Oncology
city: Cluj-Napoca
country: Romania
facility: Medisprof Cancer Center
city: Floreşti
country: Romania
facility: Centrul radioterapie Amethyst Cluj-Napoca
city: Belgrade
country: Serbia
facility: Institute of Oncology and Radiology of Serbia
city: Kragujevac
country: Serbia
facility: University Clinical Center Kragujevac
city: Sremska Kamenica
country: Serbia
facility: Institute for Oncology Vojvodina
city: Alicante
country: Spain
facility: Hospital Universitario Vinalopo
city: Badalona
country: Spain
facility: Institut Catala d'Oncologia - Hospital Duran i Reynals
city: Barcelona
country: Spain
facility: UOMI Cancer Center-Clinica Tres Torres
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia (ICO) - Hospitalet
city: Barcelona
country: Spain
facility: Vall d'Hebron Institut d'Oncologia (VHIO)
city: Cadiz
country: Spain
facility: Hospital universitario Jerez
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Grupo Hospital de Madrid (HM) - Hospital Universitario Madrid Sanchinarro - Centro Integral Oncologico Clara Campal (CIOCC)
city: Madrid
country: Spain
facility: Hospital Universitario de Torrejón
city: Málaga
country: Spain
facility: Hospital Quironsalud Malaga
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia (CHUV)
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital - Kaohsiung
city: Taichung
country: Taiwan
facility: China Medical University Hospital (CMUH)
city: Tainan
country: Taiwan
facility: National Cheng-Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital - Linkou
city: Aberdeen
country: United Kingdom
facility: NHS Grampian - Aberdeen Royal Infirmary
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute
city: Nottingham
country: United Kingdom
facility: City Hospital Nottingham
city: Sutton
country: United Kingdom
facility: The Royal Marden Hospital, Surrey
city: Torquay
country: United Kingdom
facility: Torbay Hospital
Study officials:
References: