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 5295903, Arizona 5551752, United States
The University of Arizona Cancer Center
Tucson 5318313, Arizona 5551752, United States
University of California Los Angeles
Westwood, Los Angeles 5408522, California 5332921, United States
Yale School of Medicine - Smilow Cancer Hospital
New Haven 4839366, Connecticut 4831725, United States
The George Washington University
Washington D.C. 4140963, District of Columbia 4138106, United States
AdventHealth Medical Group Oncology & Hematology at Orlando
Orlando 4167147, Florida 4155751, United States
Emory University
Atlanta 4180439, Georgia 4197000, United States
University of Illinois Cancer Center
Chicago 4887398, Illinois 4896861, United States
University of Kansas Cancer Center
Westwood 4281639, Kansas 4273857, United States
Mary Bird Perkins Cancer Center
Baton Rouge 4315588, Louisiana 4331987, United States
MaineHealth Institute for Research
South Portland 4979244, Maine 4971068, United States
University of Maryland
Baltimore 4347778, Maryland 4361885, United States
Dana Farber Cancer Institute
Boston 4930956, Massachusetts 6254926, United States
Siteman Cancer Center - Washington University
St Louis 4407066, Missouri 4398678, United States
Northwell Health Cancer Institute
Lake Success 5123853, New York 5128638, United States
Manhattan Eye, Ear & Throat Hospital
New York 5128581, New York 5128638, United States
Montefiore Medical Center
The Bronx 5110266, New York 5128638, United States
University of Cincinnati - UC Health Barrett Cancer Center
Cincinnati 4508722, Ohio 5165418, United States
Ohio State University, James Cancer Hospital and Solove Research Institute
Columbus 4509177, Ohio 5165418, United States
Fox Chase Cancer Center
Philadelphia 4560349, Pennsylvania 6254927, United States
University of Pittsburgh Medical Center - Hillman Cancer Center
Pittsburgh 5206379, Pennsylvania 6254927, United States
Medical University of South Carolina (MUSC)
Charleston 4574324, South Carolina 4597040, United States
MD Anderson Cancer Center
Houston 4699066, Texas 4736286, United States
Oncology Consultants
Houston 4699066, Texas 4736286, United States
VCU Massey Cancer Center
Richmond 4781708, Virginia 6254928, United States
Medical College of Wisconsin - Froedtert Hospital Cancer Center
Milwaukee 5263045, Wisconsin 5279468, United States
St George Hospital
Kogarah 2161185, New South Wales 2155400, Australia
St. Vincent's Hospital
Sydney 2147714, New South Wales 2155400, Australia
Princess Alexandra Hospital
Brisbane 2174003, Queensland 2152274, Australia
St. John of God Murdoch Hospital
Murdoch 8349091, Western Australia 2058645, Australia
CHU Liège
Liège 2792413, Belgium
CHU Universite Catholique de Louvain
Namur 2790471, Belgium
Vitaz-Sint-Niklaas Moerland
Sint-Niklaas 2786578, Belgium
University Hospital
Panagyurishte 728448, Bulgaria
Tom Baker Cancer Centre (Alberta Health Services)
Calgary 5913490, Alberta 5883102, Canada
Cross Cancer Institute
Edmonton 5946768, Alberta 5883102, Canada
The Ottawa Hospital Cancer Centre
Ottawa 6094817, Ontario 6093943, Canada
Princess Margaret Cancer Center - University Health Network
Toronto 6167865, Ontario 6093943, Canada
McGill University Health Centre (MUHC)
Montreal 6077243, Quebec 6115047, Canada
Fakultni nemocnice Brno
Brno 3078610, Czechia
Masaryk Memorial Cancer Institute
Brno 3078610, Czechia
Fakultni Nemocnice Olomouc
Olomouc 3069011, Czechia
Fakultni Nemocnice Kralovske Vinohrady
Prague 3067696, Czechia
Fakultni nemocnice Bulovka
Prague 3067696, Czechia
Clinique Pasteur - Lanroze- Centre Finistérien de Radiothérapie et d'Oncologie
Brest 3030300, France
Pôle Santé Léonard de Vinci
Chambray-lès-Tours 3027343, France
Centre Léon Bérard
Lyon 2996944, France
Assistance Publique Hopitaux de Marseille (APHM)-Hôpital La Timone
Marseille 2995469, France
Institut Curie
Paris 2988507, France
Hôpital Privé des Côtes d'Armor
Plérin 2986795, France
Institut Gustave Roussy
Villejuif 2968705, France
Charite-Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK) - Medizinische Klinik mit Schwerpunkt Haematologie, Onkologie und Tumorimmunologie
Berlin 2950159, Germany
UNIVERSITÄTSKLINIKUM FREIBURG, Klinik für Innere Medizin I, Schwerpunkt Hämatologie, Onkologie und Stammzelltransplantation
Freiburg im Breisgau 2925177, Germany
Ludwig-Maximilians University
Munich 2867714, Germany
Orszagos Onkologiai Intezet
Budapest 3054643, Hungary
Petz Aladar Country Teaching Hospital
Győr 3052009, Hungary
Josa Andras Oktatokorhaz
Nyíregyháza 716935, Hungary
University of Pecs - Oncology
Pécs 3046526, Hungary
Szent Lázár Megyei Kórház
Salgótarján 3045643, Hungary
IRCCS Istituto Scienze Neurologiche
Bologna 3181928, Italy
AOU Careggi
Florence 3176959, Italy
IRCCS Istituto Clinico Humanitas - Cancer center
Milan 6951411, Italy
IRCCS Ospedale San Raffaele Milano
Milan 6951411, Italy
Fondazione IRCCS - Istituto Nazionale Tumori - Oncologia
Milan 6951411, Italy
Azienda Ospedaliera Universitaria Maggiore Della Carita Novara
Novara 3172189, Italy
Istituto Oncologico Veneto
Padua 3171728, Italy
IRCCS - ICS Maugeri
Pavia 3171366, Italy
Universita degli Studi di Pavia - Fondazione IRCCS Policlinico San Matteo
Pavia 3171366, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Roma 8957247, Italy
Antoni van Leeuwenhoek
Amsterdam 2759794, Netherlands
Radboud University Medical Center
Nijmegen 2750053, Netherlands
Centrum Onkologii im. prof. F. Lukaszczyka w Bydgoszczy
Bydgoszcz 3102014, Poland
National Research Institute of Oncology
Gliwice 3099230, Poland
Medisprof Cancer Center
Cluj-Napoca 681290, Romania
Centrul radioterapie Amethyst Cluj-Napoca
Floreşti 678063, Romania
Institute of Oncology and Radiology of Serbia
Belgrade 792680, Serbia
Institute for Oncology Vojvodina
Kamenitz 3190104, Serbia
University Clinical Center Kragujevac
Kragujevac 789128, Serbia
Keimyung University Dongsan Hospital
Daegu 1835329, South Korea
Korea University Anam Hospital
Seoul 1835848, South Korea
Seoul National University Hospital
Seoul 1835848, South Korea
The Catholic University of Korea, Eunpyeong St. Mary's Hospital
Seoul 1835848, South Korea
Severance Hospital, Yonsei University Health System
Seoul 1835848, South Korea
Samsung Medical Center
Seoul 1835848, South Korea
Ajou University Hospital
Suwon 1835553, South Korea
Hospital Universitario Vinalopo
Alicante 2521978, Spain
Institut Catala d'Oncologia - Hospital Duran i Reynals
Badalona 3129028, Spain
UOMI Cancer Center-Clinica Tres Torres
Barcelona 3128760, Spain
Institut Catala d'Oncologia (ICO) - Hospitalet
Barcelona 3128760, Spain
Vall d'Hebron Institut d'Oncologia (VHIO)
Barcelona 3128760, Spain
Hospital universitario Jerez
Cadiz 2520600, Spain
Hospital Universitario La Paz
Madrid 3117735, Spain
Grupo Hospital de Madrid (HM) - Hospital Universitario Madrid Sanchinarro - Centro Integral Oncologico Clara Campal (CIOCC)
Madrid 3117735, Spain
Hospital Universitario de Torrejón
Madrid 3117735, Spain
Hospital Quironsalud Malaga
Málaga 2514256, Spain
Hospital Universitario Marques de Valdecilla
Santander 3109718, Spain
Hospital Clinico Universitario de Valencia (CHUV)
Valencia 2509954, Spain
Changhua Christian Hospital
Changhua 1993459, Taiwan
Chang Gung Memorial Hospital - Kaohsiung
Kaohsiung City 1673820, Taiwan
China Medical University Hospital (CMUH)
Taichung 1668399, Taiwan
National Cheng-Kung University Hospital
Tainan City 1668355, Taiwan
National Taiwan University Hospital
Taipei 1668341, Taiwan
Taipei Veterans General Hospital
Taipei 1668341, Taiwan
Chang Gung Memorial Hospital - Linkou
Taoyuan District 1667905, Taiwan
NHS Grampian - Aberdeen Royal Infirmary
Aberdeen 2657832, United Kingdom
The Royal Marsden NHS Foundation Trust
London 2643743, United Kingdom
Sarah Cannon Research Institute
London 2643743, United Kingdom
City Hospital Nottingham
Nottingham 2641170, United Kingdom
The Royal Marden Hospital, Surrey
Sutton 2636503, United Kingdom
Torbay Hospital
Torquay 2635650, United Kingdom
Clinical Trials Office
+1.857.400.0101
clinical@aveooncology.com
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