Metastatic Head-and-neck Squamous-cell CarcinomaPhase 3FIERCE-HNNCT06064877
A Study of Ficlatuzumab in Combination With Cetuximab in Participants With Recurrent or Metastatic (R/M) HPV Negative Head and Neck Squamous Cell Carcinoma
A Phase 3 study testing Ficlatuzumab and Cetuximab in people with Metastatic Head-and-neck Squamous-cell Carcinoma and Recurrent Head and Neck Squamous Cell Carcinoma, run by AVEO Pharmaceuticals, Inc. at 112 sites in 18 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Head-and-neck Squamous-cell Carcinoma, Recurrent Head and Neck Squamous Cell Carcinoma
- What is being tested?
- Ficlatuzumab and Cetuximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 410 participants
- Where
- 112 sitesin 18 countries
- Study dates
- 11 Jan 2024to Nov 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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):
- 2 weeks (14 days) or 5 half-lives, whichever is shorter, for chemotherapeutic agents, small molecules, and checkpoint inhibitors
- 3 weeks (21 days) or 5 half-lives, whichever is shorter, for antibody-drug conjugates
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- 4 weeks (28 days) for cell therapies
- 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 or greater 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 hepatitis B virus (HBV) or hepatitis C virus (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.
Trial locations and contacts
112 sites in 18 countries. Contact the study team or a site near you to ask about taking part.
112 sites in 18 countries
United States28 sites, 25 recruiting
- Recruiting
Emory University
Atlanta, Georgia, 30308
- Recruiting
University of Maryland
Baltimore, Maryland, 21201
- Recruiting
Mary Bird Perkins Cancer Center
Baton Rouge, Louisiana, 70809
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
- Recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
- Recruiting
Medical University of South Carolina (MUSC)
Charleston, South Carolina, 29425
- Recruiting
University of Illinois Cancer Center
Chicago, Illinois, 60612
- Withdrawn
University of Cincinnati - UC Health Barrett Cancer Center
Cincinnati, Ohio, 45219
- Recruiting
Ohio State University, James Cancer Hospital and Solove Research Institute
Columbus, Ohio, 43210
- Recruiting
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85212
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
- Recruiting
Oncology Consultants
Houston, Texas, 77030
- Recruiting
Northwell Health Cancer Institute
Lake Success, New York, 10042
- Recruiting
University of California Los Angeles
Los Angeles, California, 90024
- Terminated
Medical College of Wisconsin - Froedtert Hospital Cancer Center
Milwaukee, Wisconsin, 53202
- Recruiting
Yale School of Medicine - Smilow Cancer Hospital
New Haven, Connecticut, 06511
- Recruiting
Manhattan Eye, Ear & Throat Hospital
New York, New York, 10065
- Recruiting
AdventHealth Medical Group Oncology & Hematology at Orlando
Orlando, Florida, 32804
- Recruiting
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
- Recruiting
University of Pittsburgh Medical Center - Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
- Recruiting
VCU Massey Cancer Center
Richmond, Virginia, 23298
- Recruiting
MaineHealth Institute for Research
South Portland, Maine, 04106
- Recruiting
Siteman Cancer Center - Washington University
St Louis, Missouri, 63110
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
- Withdrawn
Montefiore Medical Center
The Bronx, New York, 10461
- Recruiting
The University of Arizona Cancer Center
Tucson, Arizona, 85719
- Recruiting
The George Washington University
Washington D.C., District of Columbia, 20052-0042
- Recruiting
University of Kansas Cancer Center
Westwood, Kansas, 66205
Spain12 sites, 11 recruiting
- Recruiting
Hospital Universitario Vinalopo
Alicante, 03293
- Recruiting
Institut Catala d'Oncologia - Hospital Duran i Reynals
Badalona, 08907
- Recruiting
UOMI Cancer Center-Clinica Tres Torres
Barcelona, 08017
- Recruiting
Institut Catala d'Oncologia (ICO) - Hospitalet
Barcelona, 08908
- Recruiting
Vall d'Hebron Institut d'Oncologia (VHIO)
Barcelona
- Recruiting
Hospital universitario Jerez
Cadiz, 11407
- Recruiting
Hospital Universitario La Paz
Madrid, 28046
- Recruiting
Grupo Hospital de Madrid (HM) - Hospital Universitario Madrid Sanchinarro - Centro Integral Oncologico Clara Campal (CIOCC)
Madrid, 28051
- Recruiting
Hospital Universitario de Torrejón
Madrid
- Recruiting
Hospital Quironsalud Malaga
Málaga, 29004
- Withdrawn
Hospital Universitario Marques de Valdecilla
Santander
- Recruiting
Hospital Clinico Universitario de Valencia (CHUV)
Valencia
Italy10 sites, 9 recruiting
- Recruiting
IRCCS Istituto Scienze Neurologiche
Bologna, 40139
- Recruiting
AOU Careggi
Florence, 51134
- Recruiting
IRCCS Istituto Clinico Humanitas - Cancer center
Milan, 20089
- Recruiting
IRCCS Ospedale San Raffaele Milano
Milan, 20132
- Recruiting
Fondazione IRCCS - Istituto Nazionale Tumori - Oncologia
Milan, 20133
- Recruiting
Azienda Ospedaliera Universitaria Maggiore Della Carita Novara
Novara, 28100
- Recruiting
Istituto Oncologico Veneto
Padua, 35128
- Recruiting
IRCCS - ICS Maugeri
Pavia, 27100
- Recruiting
Universita degli Studi di Pavia - Fondazione IRCCS Policlinico San Matteo
Pavia, 27100
- Withdrawn
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Roma, 00168
France7 sites, 6 recruiting
- Withdrawn
Clinique Pasteur - Lanroze- Centre Finistérien de Radiothérapie et d'Oncologie
Brest, 29200
- Recruiting
Pôle Santé Léonard de Vinci
Chambray-lès-Tours, 37170
- Recruiting
Centre Léon Bérard
Lyon, 69008
- Recruiting
Assistance Publique Hopitaux de Marseille (APHM)-Hôpital La Timone
Marseille, 13005
- Recruiting
Institut Curie
Paris, 75248
- Recruiting
Hôpital Privé des Côtes d'Armor
Plérin, 22190
- Recruiting
Institut Gustave Roussy
Villejuif, 94805
South Korea7 sites, 7 recruiting
- Recruiting
Keimyung University Dongsan Hospital
Daegu, 42601
- Recruiting
Korea University Anam Hospital
Seoul, 02841
- Recruiting
Seoul National University Hospital
Seoul, 03080
- Recruiting
The Catholic University of Korea, Eunpyeong St. Mary's Hospital
Seoul, 03312
- Recruiting
Severance Hospital, Yonsei University Health System
Seoul, 03722
- Recruiting
Samsung Medical Center
Seoul, 06351
- Recruiting
Ajou University Hospital
Suwon, 16499
Taiwan7 sites, 5 recruiting
- Recruiting
Changhua Christian Hospital
Changhua, 500
- Recruiting
Chang Gung Memorial Hospital - Kaohsiung
Kaohsiung City, 833401
- Recruiting
China Medical University Hospital (CMUH)
Taichung, 40447
- Withdrawn
National Cheng-Kung University Hospital
Tainan, 704017
- Withdrawn
National Taiwan University Hospital
Taipei, 100
- Recruiting
Taipei Veterans General Hospital
Taipei, 112201
- Recruiting
Chang Gung Memorial Hospital - Linkou
Taoyuan, 33305
United Kingdom6 sites, 5 recruiting
- Recruiting
NHS Grampian - Aberdeen Royal Infirmary
Aberdeen, AB25 2ZN
- Recruiting
The Royal Marsden NHS Foundation Trust
London, SW3 6JJ
- Recruiting
Sarah Cannon Research Institute
London, W1G 6AD
- Recruiting
City Hospital Nottingham
Nottingham, NG5 1PB
- Recruiting
The Royal Marden Hospital, Surrey
Sutton, SM2 5PT
- Withdrawn
Torbay Hospital
Torquay, TQ2 7AA
Canada5 sites, 4 recruiting
- Recruiting
Tom Baker Cancer Centre (Alberta Health Services)
Calgary, Alberta, T3N 4N1
- Recruiting
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
- Recruiting
McGill University Health Centre (MUHC)
Montreal, Quebec, H4A3J1
- Withdrawn
The Ottawa Hospital Cancer Centre
Ottawa, Ontario, K1H 8L6
- Recruiting
Princess Margaret Cancer Center - University Health Network
Toronto, Ontario, M5G 2M9
Czechia5 sites, 4 recruiting
- Recruiting
Fakultni nemocnice Brno
Brno, 60200
- Recruiting
Masaryk Memorial Cancer Institute
Brno, 65653
- Withdrawn
Fakultni Nemocnice Olomouc
Olomouc, 77900
- Recruiting
Fakultni Nemocnice Kralovske Vinohrady
Prague, 13400
- Recruiting
Fakultni nemocnice Bulovka
Prague
Hungary5 sites, 3 recruiting
- Not yet recruiting
Orszagos Onkologiai Intezet
Budapest, 1122
- Withdrawn
Petz Aladar Country Teaching Hospital
Győr, 9024
- Recruiting
Josa Andras Oktatokorhaz
Nyíregyháza, 4400
- Recruiting
University of Pecs - Oncology
Pécs, 7624
- Withdrawn
Szent Lázár Megyei Kórház
Salgótarján, 3100
Australia4 sites, 4 recruiting
- Recruiting
Princess Alexandra Hospital
Brisbane, Queensland, 4102
- Recruiting
St George Hospital
Kogarah, New South Wales, 2217
- Recruiting
St. John of God Murdoch Hospital
Murdoch, Western Australia, 6150
- Recruiting
St. Vincent's Hospital
Sydney, New South Wales, 2010
Belgium3 sites, 3 recruiting
- Recruiting
CHU Liège
Liège, 4000
- Recruiting
CHU Universite Catholique de Louvain
Namur, B5000
- Recruiting
Vitaz-Sint-Niklaas Moerland
Sint-Niklaas, 9100
Germany3 sites, 3 recruiting
- Recruiting
Charite-Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK) - Medizinische Klinik mit Schwerpunkt Haematologie, Onkologie und Tumorimmunologie
Berlin, 12200
- Recruiting
UNIVERSITÄTSKLINIKUM FREIBURG, Klinik für Innere Medizin I, Schwerpunkt Hämatologie, Onkologie und Stammzelltransplantation
Freiburg im Breisgau, 79106
- Recruiting
Ludwig-Maximilians University
Munich, 81377
Serbia3 sites, 3 recruiting
- Recruiting
Institute of Oncology and Radiology of Serbia
Belgrade
- Recruiting
Institute for Oncology Vojvodina
Kamenitz
- Recruiting
University Clinical Center Kragujevac
Kragujevac
Netherlands2 sites, 1 recruiting
- Withdrawn
Antoni van Leeuwenhoek
Amsterdam, 1066
- Recruiting
Radboud University Medical Center
Nijmegen, 6525
Poland2 sites, 2 recruiting
- Recruiting
Centrum Onkologii im. prof. F. Lukaszczyka w Bydgoszczy
Bydgoszcz, 85-796
- Recruiting
National Research Institute of Oncology
Gliwice, 44-100
Romania2 sites, 2 recruiting
- Recruiting
Medisprof Cancer Center
Cluj-Napoca, 400641
- Recruiting
Centrul radioterapie Amethyst Cluj-Napoca
Floreşti, 407280
About this study
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)
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.
Read the 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.
- Conditions
- Metastatic Head-and-neck Squamous-cell Carcinoma, Recurrent Head and Neck Squamous Cell Carcinoma
- Being tested
- Ficlatuzumab, Cetuximab, Placebo
- Keywords
- Recurrent, Metastatic, HPV-negative, Head and Neck, Squamous Cell Carcinoma
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Recurrence, Neoplasm Metastasis, Carcinoma, Squamous Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FiclatuzumabBiological
Also called AV-299
Ficlatuzumab (AV-299) is a humanized hepatocyte growth factor (HGF) inhibitory immunoglobulin G1 (IgG1) monoclonal antibody (mAb).
CetuximabBiological
Also called Erbitux
Cetuximab is an epidermal growth factor receptor (EGFR) antagonist.
PlaceboOther
Placebo for this study will be normal saline
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 (Investigational Arm: ficlatuzumab plus cetuximab) | Experimental | Intravenous (IV) ficlatuzumab dose A on Day 1 (D1) and D15 of each 28-day cycle IV cetuximab on D1 and D15 of each 28-day cycle Receives: Biological: Ficlatuzumab; Biological: Cetuximab |
| Arm 2 (Investigational Arm: ficlatuzumab plus cetuximab) | Experimental | IV ficlatuzumab dose B on D1 and D15 of each 28-day cycle IV cetuximab on D1 and D15 of each 28-day cycle Receives: Biological: Ficlatuzumab; Biological: Cetuximab |
| Arm 3 (Comparator Arm: placebo plus cetuximab) | Placebo comparator | IV placebo (saline, ficlatuzumab-matched) on D1 and D15 of each 28-day cycle IV cetuximab on D1 and D15 of each 28-day cycle Receives: Biological: Cetuximab; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Overall survival (OS), defined as the time from the date of randomization to the date of death for any cause
Measured: From Randomization until death from any cause (Approximately 44 months)
Secondary outcomes (9)
To evaluate progression-free survival (PFS) for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC
Progression-free survival (PFS), defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death from any cause, whichever occurs first
Measured: From Randomization until disease progression or death (Approximately 44 months)
To evaluate additional objective response rate for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC
Objective response rate (ORR), defined as the percentage of participants who have a complete response (CR) or a partial response (PR) per RECIST v1.1
Measured: 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)
To evaluate disease control rate (DCR) for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC
Disease control rate (DCR), defined for participants who have achieved a CR, PR or stable disease for at least 8 weeks per RECIST v1.1
Measured: 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)
To evaluate duration of response (DOR) for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC
Duration of response (DOR), defined as the time from first documented evidence of a confirmed CR or PR per RECIST v1.1
Measured: 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)
To compare the safety and tolerability of ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC
Number of times participants experience Adverse Events (AE) or abnormal laboratory values.
Measured: From Screening until 30 days after last dose
To evaluate the pharmacokinetics (PK) of ficlatuzumab
Serum samples will be assessed for concentrations of ficlatuzumab
Measured: From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months)
To assess the immunogenicity of ficlatuzumab via antidrug antibodies (ADAs)
Serum samples will be assessed for the presence of ADA to ficlatuzumab.
Measured: From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months)
To assess the immunogenicity of ficlatuzumab via neutralizing antibodies (nAB)
Serum samples that test positive for the presence of ADA to ficlatuzumab will be further tested for the presence of nAB.
Measured: From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months)
To evaluate the quality of life (QOL) of ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC
Change from baseline in overall health status and time to clinically meaningful deterioration based on scoring of standardized participant questionnaires
Measured: From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2023
- Study start11 Jan 2024
- Primary completionAug 2027 (estimated)
- Study completionNov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Head-and-neck Squamous-cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 410 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AVEO Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06064877
- Sponsor's protocol ID
- AV-299-23-301
- Acronym
- FIERCE-HN
- Status last verified
- Apr 2026
- First submitted
- 14 Sep 2023
- Last updated
- 9 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT06064877
- Acronym / sponsor ID
- FIERCE-HN / AV-299-23-301
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 410 participants (estimated)
- Lead sponsor
- AVEO Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 11 Jan 2024 (actual)
- Primary completion
- Aug 2027 (estimated)
- Study completion
- Nov 2027 (estimated)
- First posted
- 3 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1 (Investigational Arm: ficlatuzumab plus cetuximab) | Experimental | Biological: Ficlatuzumab, Biological: CetuximabIntravenous (IV) ficlatuzumab dose A on Day 1 (D1) and D15 of each 28-day cycle IV cetuximab on D1 and D15 of each 28-day cycle |
| Arm 2 (Investigational Arm: ficlatuzumab plus cetuximab) | Experimental | Biological: Ficlatuzumab, Biological: CetuximabIV ficlatuzumab dose B on D1 and D15 of each 28-day cycle IV cetuximab on D1 and D15 of each 28-day cycle |
| Arm 3 (Comparator Arm: placebo plus cetuximab) | Placebo comparator | Biological: Cetuximab, Other: PlaceboIV placebo (saline, ficlatuzumab-matched) on D1 and D15 of each 28-day cycle IV cetuximab on D1 and D15 of each 28-day cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (16 listed)
- 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):
- Any unresolved and significant toxicity (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 5.0) Grade 2 or greater from previous anticancer therapy (including radiation therapy), other than alopecia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FiclatuzumabAlso: AV-299Ficlatuzumab (AV-299) is a humanized hepatocyte growth factor (HGF) inhibitory immunoglobulin G1 (IgG1) monoclonal antibody (mAb). | Biological | Arm 1 (Investigational Arm: ficlatuzumab plus cetuximab), Arm 2 (Investigational Arm: ficlatuzumab plus cetuximab) |
| CetuximabAlso: ErbituxCetuximab is an epidermal growth factor receptor (EGFR) antagonist. | Biological | Arm 1 (Investigational Arm: ficlatuzumab plus cetuximab), Arm 2 (Investigational Arm: ficlatuzumab plus cetuximab), Arm 3 (Comparator Arm: placebo plus cetuximab) |
| PlaceboPlacebo for this study will be normal saline | Other | Arm 3 (Comparator Arm: placebo plus cetuximab) |
Primary outcome
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)
Time frame: From Randomization until death from any cause (Approximately 44 months)
Overall survival (OS), defined as the time from the date of randomization to the date of death for any cause
9 secondary outcomes
To evaluate progression-free survival (PFS) for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC
Time frame: From Randomization until disease progression or death (Approximately 44 months)
To evaluate additional objective response rate for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC
Time frame: 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)
To evaluate disease control rate (DCR) for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC
Time frame: 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)
To evaluate duration of response (DOR) for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC
Time frame: 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)
To compare the safety and tolerability of ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC
Time frame: From Screening until 30 days after last dose
To evaluate the pharmacokinetics (PK) of ficlatuzumab
Time frame: From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months)
To assess the immunogenicity of ficlatuzumab via antidrug antibodies (ADAs)
Time frame: From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months)
To assess the immunogenicity of ficlatuzumab via neutralizing antibodies (nAB)
Time frame: From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months)
To evaluate the quality of life (QOL) of ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC
Time frame: From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
112 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ficlatuzumab and Cetuximab in people with Metastatic Head-and-neck Squamous-cell Carcinoma and Recurrent Head and Neck Squamous Cell Carcinoma, run by AVEO Pharmaceuticals, Inc. at 112 sites in 18 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 112 sites in United States, Spain, Italy, France, South Korea and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clinical Trials Office (+1.857.400.0101, clinical@aveooncology.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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) (time frame: From Randomization until death from any cause (Approximately 44 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2026.