A Study of Ficlatuzumab in Combination With Cetuximab in Participants With Recurrent or Metastatic (R/M) HPV Negative Head and Neck Squamous Cell Carcinoma
- Conditions
- Metastatic Head-and-neck Squamous-cell CarcinomaRecurrent Head and Neck Squamous Cell Carcinoma
- Interventions
- Registration Number
- NCT06064877
- Lead Sponsor
- AVEO Pharmaceuticals, Inc.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 410
- 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)
-
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
- 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 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 2 (Investigational Arm: ficlatuzumab plus cetuximab) Ficlatuzumab IV ficlatuzumab dose B on D1 and D15 of each 28-day cycle IV cetuximab on D1 and D15 of each 28-day cycle Arm 1 (Investigational Arm: ficlatuzumab plus cetuximab) Ficlatuzumab 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 Arm 3 (Comparator Arm: placebo plus cetuximab) Cetuximab 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 Arm 3 (Comparator Arm: placebo plus cetuximab) Placebo 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 Arm 1 (Investigational Arm: ficlatuzumab plus cetuximab) Cetuximab 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 Arm 2 (Investigational Arm: ficlatuzumab plus cetuximab) Cetuximab IV ficlatuzumab dose B on D1 and D15 of each 28-day cycle IV cetuximab on D1 and D15 of each 28-day cycle
- Primary Outcome Measures
Name Time Method 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) 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
- Secondary Outcome Measures
Name Time Method To assess the immunogenicity of ficlatuzumab via antidrug antibodies (ADAs) From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months) Serum samples will be assessed for the presence of ADA to ficlatuzumab.
To evaluate progression-free survival (PFS) for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC From Randomization until disease progression or death (Approximately 44 months) 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
To evaluate additional objective response rate for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC 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) 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
To evaluate disease control rate (DCR) for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC 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) 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
To evaluate duration of response (DOR) for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC 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) Duration of response (DOR), defined as the time from first documented evidence of a confirmed CR or PR per RECIST v1.1
To compare the safety and tolerability of ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC From Screening until 30 days after last dose Number of times participants experience Adverse Events (AE) or abnormal laboratory values.
To evaluate the pharmacokinetics (PK) of ficlatuzumab From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months) Serum samples will be assessed for concentrations of ficlatuzumab
To assess the immunogenicity of ficlatuzumab via neutralizing antibodies (nAB) From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months) Serum samples that test positive for the presence of ADA to ficlatuzumab will be further tested for the presence of nAB.
To evaluate the quality of life (QOL) of ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months) Change from baseline in overall health status and time to clinically meaningful deterioration based on scoring of standardized participant questionnaires
Trial Locations
- Locations (110)
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
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Spain
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
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
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
Hospital Clinico Universitario de Valencia (CHUV)
🇪🇸Valencia, Spain
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
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