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

NCT ID: NCT06064877

Last Updated: 2025-04-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

410 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-01-11

Study Completion Date

2027-11-30

Brief Summary

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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

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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

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Double-Blind, Placebo-Controlled

Study Groups

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Arm 1 (Investigational Arm: ficlatuzumab plus 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

Group Type EXPERIMENTAL

Ficlatuzumab

Intervention Type BIOLOGICAL

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

Cetuximab

Intervention Type BIOLOGICAL

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

Arm 2 (Investigational Arm: ficlatuzumab plus 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

Group Type EXPERIMENTAL

Ficlatuzumab

Intervention Type BIOLOGICAL

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

Cetuximab

Intervention Type BIOLOGICAL

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

Arm 3 (Comparator Arm: placebo plus 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

Group Type PLACEBO_COMPARATOR

Cetuximab

Intervention Type BIOLOGICAL

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

Placebo

Intervention Type OTHER

Placebo for this study will be normal saline

Interventions

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Ficlatuzumab

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

Intervention Type BIOLOGICAL

Cetuximab

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

Intervention Type BIOLOGICAL

Placebo

Placebo for this study will be normal saline

Intervention Type OTHER

Other Intervention Names

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AV-299 Erbitux

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AVEO Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status RECRUITING

The University of Arizona Cancer Center

Tucson, Arizona, United States

Site Status RECRUITING

University of California Los Angeles

Westwood, Los Angeles, California, United States

Site Status RECRUITING

Yale School of Medicine - Smilow Cancer Hospital

New Haven, Connecticut, United States

Site Status RECRUITING

The George Washington University

Washington D.C., District of Columbia, United States

Site Status RECRUITING

AdventHealth Medical Group Oncology & Hematology at Orlando

Orlando, Florida, United States

Site Status RECRUITING

Emory University

Atlanta, Georgia, United States

Site Status RECRUITING

University of Illinois Cancer Center

Chicago, Illinois, United States

Site Status RECRUITING

University of Kansas Cancer Center

Westwood, Kansas, United States

Site Status RECRUITING

Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, United States

Site Status RECRUITING

MaineHealth Institute for Research

South Portland, Maine, United States

Site Status RECRUITING

University of Maryland

Baltimore, Maryland, United States

Site Status RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Siteman Cancer Center - Washington University

St Louis, Missouri, United States

Site Status RECRUITING

Northwell Health Cancer Institute

Lake Success, New York, United States

Site Status RECRUITING

Manhattan Eye, Ear & Throat Hospital

New York, New York, United States

Site Status RECRUITING

Montefiore Medical Center

The Bronx, New York, United States

Site Status RECRUITING

University of Cincinnati - UC Health Barrett Cancer Center

Cincinnati, Ohio, United States

Site Status RECRUITING

Ohio State University, James Cancer Hospital and Solove Research Institute

Columbus, Ohio, United States

Site Status RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

University of Pittsburgh Medical Center - Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Medical University of South Carolina (MUSC)

Charleston, South Carolina, United States

Site Status RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Oncology Consultants

Houston, Texas, United States

Site Status RECRUITING

VCU Massey Cancer Center

Richmond, Virginia, United States

Site Status RECRUITING

Medical College of Wisconsin - Froedtert Hospital Cancer Center

Milwaukee, Wisconsin, United States

Site Status RECRUITING

St George Hospital

Kogarah, New South Wales, Australia

Site Status RECRUITING

St. Vincent's Hospital

Sydney, New South Wales, Australia

Site Status RECRUITING

Princess Alexandra Hospital

Brisbane, Queensland, Australia

Site Status RECRUITING

St. John of God Murdoch Hospital

Murdoch, Western Australia, Australia

Site Status RECRUITING

CHU Liège

Liège, , Belgium

Site Status RECRUITING

CHU Universite Catholique de Louvain

Namur, , Belgium

Site Status RECRUITING

Vitaz-Sint-Niklaas Moerland

Sint-Niklaas, , Belgium

Site Status RECRUITING

University Hospital

Panagyurishte, , Bulgaria

Site Status RECRUITING

Tom Baker Cancer Centre (Alberta Health Services)

Calgary, Alberta, Canada

Site Status RECRUITING

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status RECRUITING

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

Site Status RECRUITING

Princess Margaret Cancer Center - University Health Network

Toronto, Ontario, Canada

Site Status RECRUITING

McGill University Health Centre (MUHC)

Montreal, Quebec, Canada

Site Status RECRUITING

Fakultni nemocnice Brno

Brno, , Czechia

Site Status RECRUITING

Masaryk Memorial Cancer Institute

Brno, , Czechia

Site Status RECRUITING

Fakultni Nemocnice Olomouc

Olomouc, , Czechia

Site Status RECRUITING

Fakultni Nemocnice Kralovske Vinohrady

Prague, , Czechia

Site Status RECRUITING

Fakultni nemocnice Bulovka

Prague, , Czechia

Site Status RECRUITING

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

Brest, , France

Site Status RECRUITING

Pôle Santé Léonard de Vinci

Chambray-lès-Tours, , France

Site Status RECRUITING

Centre Léon Bérard

Lyon, , France

Site Status RECRUITING

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

Marseille, , France

Site Status RECRUITING

Institut Curie

Paris, , France

Site Status RECRUITING

Hôpital Privé des Côtes d'Armor

Plérin, , France

Site Status RECRUITING

Institut Gustave Roussy

Villejuif, , France

Site Status RECRUITING

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

Berlin, , Germany

Site Status RECRUITING

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

Freiburg im Breisgau, , Germany

Site Status RECRUITING

Ludwig-Maximilians University

Munich, , Germany

Site Status RECRUITING

Orszagos Onkologiai Intezet

Budapest, , Hungary

Site Status NOT_YET_RECRUITING

Petz Aladar Country Teaching Hospital

Győr, , Hungary

Site Status WITHDRAWN

Josa Andras Oktatokorhaz

Nyíregyháza, , Hungary

Site Status RECRUITING

University of Pecs - Oncology

Pécs, , Hungary

Site Status RECRUITING

Szent Lázár Megyei Kórház

Salgótarján, , Hungary

Site Status NOT_YET_RECRUITING

IRCCS Istituto Scienze Neurologiche

Bologna, , Italy

Site Status RECRUITING

AOU Careggi

Florence, , Italy

Site Status RECRUITING

IRCCS Istituto Clinico Humanitas - Cancer center

Milan, , Italy

Site Status RECRUITING

IRCCS Ospedale San Raffaele Milano

Milan, , Italy

Site Status RECRUITING

Fondazione IRCCS - Istituto Nazionale Tumori - Oncologia

Milan, , Italy

Site Status RECRUITING

Azienda Ospedaliera Universitaria Maggiore Della Carita Novara

Novara, , Italy

Site Status RECRUITING

Istituto Oncologico Veneto

Padua, , Italy

Site Status RECRUITING

IRCCS - ICS Maugeri

Pavia, , Italy

Site Status RECRUITING

Universita degli Studi di Pavia - Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Site Status RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, , Italy

Site Status WITHDRAWN

Antoni van Leeuwenhoek

Amsterdam, , Netherlands

Site Status RECRUITING

Radboud University Medical Center

Nijmegen, , Netherlands

Site Status RECRUITING

Centrum Onkologii im. prof. F. Lukaszczyka w Bydgoszczy

Bydgoszcz, , Poland

Site Status RECRUITING

National Research Institute of Oncology

Gliwice, , Poland

Site Status RECRUITING

Medisprof Cancer Center

Cluj-Napoca, , Romania

Site Status RECRUITING

Centrul radioterapie Amethyst Cluj-Napoca

Floreşti, , Romania

Site Status RECRUITING

Institute of Oncology and Radiology of Serbia

Belgrade, , Serbia

Site Status NOT_YET_RECRUITING

Institute for Oncology Vojvodina

Kamenitz, , Serbia

Site Status RECRUITING

University Clinical Center Kragujevac

Kragujevac, , Serbia

Site Status NOT_YET_RECRUITING

Keimyung University Dongsan Hospital

Daegu, , South Korea

Site Status RECRUITING

Korea University Anam Hospital

Seoul, , South Korea

Site Status RECRUITING

Seoul National University Hospital

Seoul, , South Korea

Site Status RECRUITING

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

Seoul, , South Korea

Site Status RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status RECRUITING

Samsung Medical Center

Seoul, , South Korea

Site Status RECRUITING

Ajou University Hospital

Suwon, , South Korea

Site Status RECRUITING

Hospital Universitario Vinalopo

Alicante, , Spain

Site Status RECRUITING

Institut Catala d'Oncologia - Hospital Duran i Reynals

Badalona, , Spain

Site Status RECRUITING

UOMI Cancer Center-Clinica Tres Torres

Barcelona, , Spain

Site Status RECRUITING

Institut Catala d'Oncologia (ICO) - Hospitalet

Barcelona, , Spain

Site Status RECRUITING

Vall d'Hebron Institut d'Oncologia (VHIO)

Barcelona, , Spain

Site Status RECRUITING

Hospital universitario Jerez

Cadiz, , Spain

Site Status RECRUITING

Hospital Universitario La Paz

Madrid, , Spain

Site Status RECRUITING

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

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario de Torrejón

Madrid, , Spain

Site Status RECRUITING

Hospital Quironsalud Malaga

Málaga, , Spain

Site Status RECRUITING

Hospital Universitario Marques de Valdecilla

Santander, , Spain

Site Status NOT_YET_RECRUITING

Hospital Clinico Universitario de Valencia (CHUV)

Valencia, , Spain

Site Status RECRUITING

Changhua Christian Hospital

Changhua, , Taiwan

Site Status RECRUITING

Chang Gung Memorial Hospital - Kaohsiung

Kaohsiung City, , Taiwan

Site Status RECRUITING

China Medical University Hospital (CMUH)

Taichung, , Taiwan

Site Status RECRUITING

National Cheng-Kung University Hospital

Tainan City, , Taiwan

Site Status RECRUITING

National Taiwan University Hospital

Taipei, , Taiwan

Site Status RECRUITING

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status RECRUITING

Chang Gung Memorial Hospital - Linkou

Taoyuan District, , Taiwan

Site Status RECRUITING

NHS Grampian - Aberdeen Royal Infirmary

Aberdeen, , United Kingdom

Site Status RECRUITING

The Royal Marsden NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

Sarah Cannon Research Institute

London, , United Kingdom

Site Status RECRUITING

City Hospital Nottingham

Nottingham, , United Kingdom

Site Status RECRUITING

The Royal Marden Hospital, Surrey

Sutton, , United Kingdom

Site Status RECRUITING

Torbay Hospital

Torquay, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Belgium Bulgaria Canada Czechia France Germany Hungary Italy Netherlands Poland Romania Serbia South Korea Spain Taiwan United Kingdom

Central Contacts

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Clinical Trials Office

Role: CONTACT

+1.857.400.0101

Other Identifiers

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AV-299-23-301

Identifier Type: -

Identifier Source: org_study_id

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