A Study of Ficlatuzumab in Combination With Cetuximab in Participants With Recurrent or Metastatic (R/M) HPV Negative Head and Neck Squamous Cell Carcinoma

NCT06064877 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: AV-299-23-301
• Study Type: interventional
• Target: 410
• Locations: 18 countries
• Sites: 112

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.

Conditions

Recurrent Head and Neck Squamous Cell Carcinoma; Metastatic Head-and-neck Squamous-cell Carcinoma

Keywords

Recurrent; Metastatic; HPV-negative; Head and Neck; Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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

  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

  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

  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

  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

  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

  From Screening until 30 days after last dose

Study Arms (3)

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

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

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

Biological: Cetuximab; Other: Placebo

Interventions

Ficlatuzumab BIOLOGICAL

Ficlatuzumab (AV-299) is a humanized hepatocyte growth factor (HGF) inhibitory immunoglobulin G1 (IgG1) monoclonal antibody (mAb).

Also known as: AV-299

Arm 1 (Investigational Arm: ficlatuzumab plus cetuximab); Arm 2 (Investigational Arm: ficlatuzumab plus cetuximab)

Cetuximab BIOLOGICAL

Cetuximab is an epidermal growth factor receptor (EGFR) antagonist.

Also known as: Erbitux

Arm 1 (Investigational Arm: ficlatuzumab plus cetuximab); Arm 2 (Investigational Arm: ficlatuzumab plus cetuximab); Arm 3 (Comparator Arm: placebo plus cetuximab)

Placebo OTHER

Placebo for this study will be normal saline

Arm 3 (Comparator Arm: placebo plus cetuximab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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):
• weeks (14 days) or 5 half-lives, whichever is shorter, for chemotherapeutic agents, small molecules, and checkpoint inhibitors
• weeks (21 days) or 5 half-lives, whichever is shorter, for antibody-drug conjugates
• weeks (28 days) for cell therapies
• 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

Sponsors & Collaborators

• AVEO Pharmaceuticals, Inc.: lead

Study Sites (112)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85212, United States

RECRUITING

The University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

RECRUITING

University of California Los Angeles

Los Angeles, California, 90024, United States

RECRUITING

Yale School of Medicine - Smilow Cancer Hospital

New Haven, Connecticut, 06511, United States

RECRUITING

The George Washington University

Washington D.C., District of Columbia, 20052-0042, United States

RECRUITING

AdventHealth Medical Group Oncology & Hematology at Orlando

Orlando, Florida, 32804, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Emory University

Atlanta, Georgia, 30308, United States

RECRUITING

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

RECRUITING

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

RECRUITING

Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, 70809, United States

RECRUITING

MaineHealth Institute for Research

South Portland, Maine, 04106, United States

RECRUITING

University of Maryland

Baltimore, Maryland, 21201, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Siteman Cancer Center - Washington University

St Louis, Missouri, 63110, United States

RECRUITING

Northwell Health Cancer Institute

Lake Success, New York, 10042, United States

RECRUITING

Manhattan Eye, Ear & Throat Hospital

New York, New York, 10065, United States

RECRUITING

Montefiore Medical Center

The Bronx, New York, 10461, United States

WITHDRAWN

University of Cincinnati - UC Health Barrett Cancer Center

Cincinnati, Ohio, 45219, United States

WITHDRAWN

Ohio State University, James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43210, United States

RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

RECRUITING

University of Pittsburgh Medical Center - Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Oncology Consultants

Houston, Texas, 77030, United States

RECRUITING

VCU Massey Cancer Center

Richmond, Virginia, 23298, United States

RECRUITING

Medical College of Wisconsin - Froedtert Hospital Cancer Center

Milwaukee, Wisconsin, 53202, United States

TERMINATED

St George Hospital

Kogarah, New South Wales, 2217, Australia

RECRUITING

St. Vincent's Hospital

Sydney, New South Wales, 2010, Australia

RECRUITING

Princess Alexandra Hospital

Brisbane, Queensland, 4102, Australia

RECRUITING

St. John of God Murdoch Hospital

Murdoch, Western Australia, 6150, Australia

RECRUITING

CHU Liège

Liège, 4000, Belgium

RECRUITING

CHU Universite Catholique de Louvain

Namur, B5000, Belgium

RECRUITING

Vitaz-Sint-Niklaas Moerland

Sint-Niklaas, 9100, Belgium

RECRUITING

University Hospital

Panagyurishte, 4500, Bulgaria

WITHDRAWN

Tom Baker Cancer Centre (Alberta Health Services)

Calgary, Alberta, T3N 4N1, Canada

RECRUITING

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

RECRUITING

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, K1H 8L6, Canada

WITHDRAWN

Princess Margaret Cancer Center - University Health Network

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

McGill University Health Centre (MUHC)

Montreal, Quebec, H4A3J1, Canada

RECRUITING

Fakultni nemocnice Brno

Brno, 60200, Czechia

RECRUITING

Masaryk Memorial Cancer Institute

Brno, 65653, Czechia

RECRUITING

Fakultni Nemocnice Olomouc

Olomouc, 77900, Czechia

WITHDRAWN

Fakultni Nemocnice Kralovske Vinohrady

Prague, 13400, Czechia

RECRUITING

Fakultni nemocnice Bulovka

Prague, Czechia

RECRUITING

Clinique Pasteur - Lanroze- Centre Finistérien de Radiothérapie et d'Oncologie

Brest, 29200, France

WITHDRAWN

Pôle Santé Léonard de Vinci

Chambray-lès-Tours, 37170, France

RECRUITING

Centre Léon Bérard

Lyon, 69008, France

RECRUITING

Assistance Publique Hopitaux de Marseille (APHM)-Hôpital La Timone

Marseille, 13005, France

RECRUITING

Institut Curie

Paris, 75248, France

RECRUITING

Hôpital Privé des Côtes d'Armor

Plérin, 22190, France

RECRUITING

Institut Gustave Roussy

Villejuif, 94805, France

RECRUITING

Charite-Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK) - Medizinische Klinik mit Schwerpunkt Haematologie, Onkologie und Tumorimmunologie

Berlin, 12200, Germany

RECRUITING

UNIVERSITÄTSKLINIKUM FREIBURG, Klinik für Innere Medizin I, Schwerpunkt Hämatologie, Onkologie und Stammzelltransplantation

Freiburg im Breisgau, 79106, Germany

RECRUITING

Ludwig-Maximilians University

Munich, 81377, Germany

RECRUITING

Orszagos Onkologiai Intezet

Budapest, 1122, Hungary

NOT YET RECRUITING

Petz Aladar Country Teaching Hospital

Győr, 9024, Hungary

WITHDRAWN

Josa Andras Oktatokorhaz

Nyíregyháza, 4400, Hungary

RECRUITING

University of Pecs - Oncology

Pécs, 7624, Hungary

RECRUITING

Szent Lázár Megyei Kórház

Salgótarján, 3100, Hungary

WITHDRAWN

IRCCS Istituto Scienze Neurologiche

Bologna, 40139, Italy

RECRUITING

AOU Careggi

Florence, 51134, Italy

RECRUITING

IRCCS Istituto Clinico Humanitas - Cancer center

Milan, 20089, Italy

RECRUITING

IRCCS Ospedale San Raffaele Milano

Milan, 20132, Italy

RECRUITING

Fondazione IRCCS - Istituto Nazionale Tumori - Oncologia

Milan, 20133, Italy

RECRUITING

Azienda Ospedaliera Universitaria Maggiore Della Carita Novara

Novara, 28100, Italy

RECRUITING

Istituto Oncologico Veneto

Padua, 35128, Italy

RECRUITING

IRCCS - ICS Maugeri

Pavia, 27100, Italy

RECRUITING

Universita degli Studi di Pavia - Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

WITHDRAWN

Antoni van Leeuwenhoek

Amsterdam, 1066, Netherlands

WITHDRAWN

Radboud University Medical Center

Nijmegen, 6525, Netherlands

RECRUITING

Centrum Onkologii im. prof. F. Lukaszczyka w Bydgoszczy

Bydgoszcz, 85-796, Poland

RECRUITING

National Research Institute of Oncology

Gliwice, 44-100, Poland

RECRUITING

Medisprof Cancer Center

Cluj-Napoca, 400641, Romania

RECRUITING

Centrul radioterapie Amethyst Cluj-Napoca

Floreşti, 407280, Romania

RECRUITING

Institute of Oncology and Radiology of Serbia

Belgrade, Serbia

RECRUITING

Institute for Oncology Vojvodina

Kamenitz, Serbia

RECRUITING

University Clinical Center Kragujevac

Kragujevac, Serbia

RECRUITING

Keimyung University Dongsan Hospital

Daegu, 42601, South Korea

RECRUITING

Korea University Anam Hospital

Seoul, 02841, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

The Catholic University of Korea, Eunpyeong St. Mary's Hospital

Seoul, 03312, South Korea

RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

Ajou University Hospital

Suwon, 16499, South Korea

RECRUITING

Hospital Universitario Vinalopo

Alicante, 03293, Spain

RECRUITING

Institut Catala d'Oncologia - Hospital Duran i Reynals

Badalona, 08907, Spain

RECRUITING

UOMI Cancer Center-Clinica Tres Torres

Barcelona, 08017, Spain

RECRUITING

Institut Catala d'Oncologia (ICO) - Hospitalet

Barcelona, 08908, Spain

RECRUITING

Vall d'Hebron Institut d'Oncologia (VHIO)

Barcelona, Spain

RECRUITING

Hospital universitario Jerez

Cadiz, 11407, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

Grupo Hospital de Madrid (HM) - Hospital Universitario Madrid Sanchinarro - Centro Integral Oncologico Clara Campal (CIOCC)

Madrid, 28051, Spain

RECRUITING

Hospital Universitario de Torrejón

Madrid, Spain

RECRUITING

Hospital Quironsalud Malaga

Málaga, 29004, Spain

RECRUITING

Hospital Universitario Marques de Valdecilla

Santander, Spain

WITHDRAWN

Hospital Clinico Universitario de Valencia (CHUV)

Valencia, Spain

RECRUITING

Changhua Christian Hospital

Changhua, 500, Taiwan

RECRUITING

Chang Gung Memorial Hospital - Kaohsiung

Kaohsiung City, 833401, Taiwan

RECRUITING

China Medical University Hospital (CMUH)

Taichung, 40447, Taiwan

RECRUITING

National Cheng-Kung University Hospital

Tainan, 704017, Taiwan

WITHDRAWN

National Taiwan University Hospital

Taipei, 100, Taiwan

WITHDRAWN

Taipei Veterans General Hospital

Taipei, 112201, Taiwan

RECRUITING

Chang Gung Memorial Hospital - Linkou

Taoyuan District, 33305, Taiwan

RECRUITING

NHS Grampian - Aberdeen Royal Infirmary

Aberdeen, AB25 2ZN, United Kingdom

RECRUITING

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

RECRUITING

Sarah Cannon Research Institute

London, W1G 6AD, United Kingdom

RECRUITING

City Hospital Nottingham

Nottingham, NG5 1PB, United Kingdom

RECRUITING

The Royal Marden Hospital, Surrey

Sutton, SM2 5PT, United Kingdom

RECRUITING

Torbay Hospital

Torquay, TQ2 7AA, United Kingdom

WITHDRAWN

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Recurrence; Neoplasm Metastasis; Carcinoma, Squamous Cell

Interventions

ficlatuzumab; Cetuximab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Clinical Trials Office

CONTACT

+1.857.400.0101; clinical@aveooncology.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-Blind, Placebo-Controlled
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2023
• First Posted: October 3, 2023
• Study Start: January 11, 2024
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: April 9, 2026

Record last verified: 2026-04

Locations

DE (3); BU (1); SE (3); US (28); CA (5); KR (7); HU (5); NL (2); ES (12); TW (7); BE (3); CZ (5); AU (4); FR (7); RO (2); GB (6); IT (10); PL (2)