The purpose of this study is to compare the efficacy and safety of ficlatuzumab pluscetuximab 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 tocetuximab alone in terms of progression-free survival and/or overall survival.
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.
Biological: Ficlatuzumab
Ficlatuzumab (AV-299) is a humanized hepatocyte growth factor (HGF) inhibitory
immunoglobulin G1 (IgG1) monoclonal antibody (mAb).
Other Name: AV-299
Biological: Cetuximab
Cetuximab is an epidermal growth factor receptor (EGFR) antagonist.
Other Name: Erbitux
Other: Placebo
Placebo for this study will be normal saline
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.
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States
The University of Arizona Cancer Center
Tucson, Arizona, United States
University of California Los Angeles
Westwood, California, United States
Yale School of Medicine - Smilow Cancer Hospital
New Haven, Connecticut, United States
The George Washington University
Washington, District of Columbia, United States
AdventHealth Medical Group Oncology & Hematology at Orlando
Orlando, Florida, United States
Emory University
Atlanta, Georgia, United States
University of Illinois Cancer Center
Chicago, Illinois, United States
University of Kansas Cancer Center
Westwood, Kansas, United States
Mary Bird Perkins Cancer Center
Baton Rouge, Louisiana, United States
MaineHealth Institute for Research
South Portland, Maine, United States
University of Maryland
Baltimore, Maryland, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Siteman Cancer Center - Washington University
Saint Louis, Missouri, United States
Montefiore Medical Center
Bronx, New York, United States
Northwell Health Cancer Institute
Lake Success, New York, United States
Manhattan Eye, Ear & Throat Hospital
New York, New York, United States
University of Cincinnati - UC Health Barrett Cancer Center
Cincinnati, Ohio, United States
Ohio State University, James Cancer Hospital and Solove Research Institute
Columbus, Ohio, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center - Hillman Cancer Center
Pittsburg, Pennsylvania, United States
Medical University of South Carolina (MUSC)
Charleston, South Carolina, United States
MD Anderson Cancer Center
Houston, Texas, United States
Oncology Consultants
Houston, Texas, United States
VCU Massey Cancer Center
Richmond, Virginia, United States
Medical College of Wisconsin - Froedtert Hospital Cancer Center
Milwaukee, Wisconsin, United States
St George Hospital
Kogarah, New South Wales, Australia
St. Vincent's Hospital
Sydney, New South Wales, Australia
Princess Alexandra Hospital
Brisbane, Queensland, Australia
St. John of God Murdoch Hospital
Murdoch, Western Australia, Australia
CHU Liège
Liège, Belgium
CHU Universite Catholique de Louvain
Namur, Belgium
Vitaz-Sint-Niklaas Moerland
Sint-Niklaas, Belgium
University Hospital
Panagyurishte, Bulgaria
Tom Baker Cancer Centre (Alberta Health Services)
Calgary, Alberta, Canada
Cross Cancer Institute
Edmonton, Alberta, Canada
The Ottawa Hospital Cancer Centre
Ottawa, Ontario, Canada
Princess Margaret Cancer Center - University Health Network
Toronto, Ontario, Canada
McGill University Health Centre (MUHC)
Montréal, Quebec, Canada
Fakultni nemocnice Brno
Brno, Czechia
Masaryk Memorial Cancer Institute
Brno, Czechia
Fakultni Nemocnice Olomouc
Olomouc, Czechia
Fakultni Nemocnice Kralovske Vinohrady
Prague, Czechia
Fakultni nemocnice Bulovka
Prague, Czechia
Clinique Pasteur - Lanroze- Centre Finistérien de Radiothérapie et d'Oncologie
Brest, France
Pôle Santé Léonard de Vinci
Chambray-lès-Tours, France
Centre Léon Bérard
Lyon, France
Assistance Publique Hopitaux de Marseille (APHM)-Hôpital La Timone
Marseille, France
Institut Curie
Paris, France
Hôpital Privé des Côtes d'Armor
Plérin, France
Institut Gustave Roussy
Villejuif, France
Charite-Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK) - Medizinische Klinik mit Schwerpunkt Haematologie, Onkologie und Tumorimmunologie
Berlin, Germany
UNIVERSITÄTSKLINIKUM FREIBURG, Klinik für Innere Medizin I, Schwerpunkt Hämatologie, Onkologie und Stammzelltransplantation
Freiburg, Germany
Ludwig-Maximilians University
Munich, Germany
Orszagos Onkologiai Intezet
Budapest, Hungary
Petz Aladar Country Teaching Hospital
Győr, Hungary
Josa Andras Oktatokorhaz
Nyíregyháza, Hungary
University of Pecs - Oncology
Pécs, Hungary
Szent Lázár Megyei Kórház
Salgótarján, Hungary
IRCCS Istituto Scienze Neurologiche
Bologna, Italy
AOU Careggi
Firenze, Italy
IRCCS Istituto Clinico Humanitas - Cancer center
Milano, Italy
IRCCS Ospedale San Raffaele Milano
Milano, Italy
Fondazione IRCCS - Istituto Nazionale Tumori - Oncologia
Milano, Italy
Azienda Ospedaliera Universitaria Maggiore Della Carita Novara
Novara, Italy
Istituto Oncologico Veneto
Padua, Italy
IRCCS - ICS Maugeri
Pavia, Italy
Universita degli Studi di Pavia - Fondazione IRCCS Policlinico San Matteo
Pavia, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Roma, Italy
Keimyung University Dongsan Hospital
Daegu, Korea, Republic of
Korea University Anam Hospital
Seoul, Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of
The Catholic University of Korea, Eunpyeong St. Mary's Hospital
Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
Seoul, Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of
Ajou University Hospital
Suwon, Korea, Republic of
Antoni van Leeuwenhoek
Amsterdam, Netherlands
Radboud University Medical Center
Nijmegen, Netherlands
Centrum Onkologii im. prof. F. Lukaszczyka w Bydgoszczy
Bydgoszcz, Poland
National Research Institute of Oncology
Gliwice, Poland
Medisprof Cancer Center
Cluj-Napoca, Romania
Centrul radioterapie Amethyst Cluj-Napoca
Floreşti, Romania
Institute of Oncology and Radiology of Serbia
Belgrade, Serbia
University Clinical Center Kragujevac
Kragujevac, Serbia
Institute for Oncology Vojvodina
Sremska Kamenica, Serbia
Hospital Universitario Vinalopo
Alicante, Spain
Institut Catala d'Oncologia - Hospital Duran i Reynals
Badalona, Spain
UOMI Cancer Center-Clinica Tres Torres
Barcelona, Spain
Institut Catala d'Oncologia (ICO) - Hospitalet
Barcelona, Spain
Vall d'Hebron Institut d'Oncologia (VHIO)
Barcelona, Spain
Hospital universitario Jerez
Cadiz, Spain
Hospital Universitario La Paz
Madrid, Spain
Grupo Hospital de Madrid (HM) - Hospital Universitario Madrid Sanchinarro - Centro Integral Oncologico Clara Campal (CIOCC)
Madrid, Spain
Hospital Universitario de Torrejón
Madrid, Spain
Hospital Quironsalud Malaga
Málaga, Spain
Hospital Universitario Marques de Valdecilla
Santander, Spain
Hospital Clinico Universitario de Valencia (CHUV)
Valencia, Spain
Changhua Christian Hospital
Changhua, Taiwan
Chang Gung Memorial Hospital - Kaohsiung
Kaohsiung, Taiwan
China Medical University Hospital (CMUH)
Taichung, Taiwan
National Cheng-Kung University Hospital
Tainan, Taiwan
National Taiwan University Hospital
Taipei, Taiwan
Taipei Veterans General Hospital
Taipei, Taiwan
Chang Gung Memorial Hospital - Linkou
Taoyuan, Taiwan
NHS Grampian - Aberdeen Royal Infirmary
Aberdeen, United Kingdom
The Royal Marsden NHS Foundation Trust
London, United Kingdom
Sarah Cannon Research Institute
London, United Kingdom
City Hospital Nottingham
Nottingham, United Kingdom
The Royal Marden Hospital, Surrey
Sutton, United Kingdom
Torbay Hospital
Torquay, United Kingdom
Clinical Trials Office
+1.857.400.0101
clinical@aveooncology.com
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