Recruiting
Phase 3

Ficlatuzumab & Cetuximab

Sponsor:

AVEO Pharmaceuticals, Inc.

Code:

NCT06064877

Conditions

Metastatic Head-and-neck Squamous-cell Carcinoma

Recurrent Head and Neck Squamous Cell Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Ficlatuzumab

Cetuximab

Placebo

Study Details

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

Metastatic Head-and-neck Squamous-cell Carcinoma

Recurrent Head and Neck Squamous Cell Carcinoma

Study ID

NCT06064877

Start date

Jan 11, 2024

Status verified date

Apr, 2026

Completion date

Nov, 2027

Anticipated

Primary completion date

Aug, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 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

A full list of inclusion and exclusion criteria can be found in the protocol.

Study Design

Enrollment

410 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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

experimental: 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

placebo comparator: 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

Interventions

Ficlatuzumab

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

Cetuximab

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

Placebo

Placebo for this study will be normal saline

Primary outcome measure

  • 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) [ Time Frame: From Randomization until death from any cause (Approximately 44 months) ]

Central Contacts and Locations

Central contacts

Clinical Trials Office

+1.857.400.0101clinical@aveooncology.com

Locations

Banner MD Anderson Cancer Center

Recruiting

Gilbert, Arizona, United States, 85212

The University of Arizona Cancer Center

Recruiting

Tucson, Arizona, United States, 85719

University of California Los Angeles

Recruiting

Los Angeles, California, United States, 90024

Yale School of Medicine - Smilow Cancer Hospital

Recruiting

New Haven, Connecticut, United States, 06511

The George Washington University

Recruiting

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

AdventHealth Medical Group Oncology & Hematology at Orlando

Recruiting

Orlando, Florida, United States, 32804

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33612

Emory University

Recruiting

Atlanta, Georgia, United States, 30308

University of Illinois Cancer Center

Recruiting

Chicago, Illinois, United States, 60612

University of Kansas Cancer Center

Recruiting

Westwood, Kansas, United States, 66205

Mary Bird Perkins Cancer Center

Recruiting

Baton Rouge, Louisiana, United States, 70809

MaineHealth Institute for Research

Recruiting

South Portland, Maine, United States, 04106

University of Maryland

Recruiting

Baltimore, Maryland, United States, 21201

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Dana Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Siteman Cancer Center - Washington University

Recruiting

St Louis, Missouri, United States, 63110

Northwell Health Cancer Institute

Recruiting

Lake Success, New York, United States, 10042

Manhattan Eye, Ear & Throat Hospital

Recruiting

New York, New York, United States, 10065

Ohio State University, James Cancer Hospital and Solove Research Institute

Recruiting

Columbus, Ohio, United States, 43210

Fox Chase Cancer Center

Recruiting

Philadelphia, Pennsylvania, United States, 19111

University of Pittsburgh Medical Center - Hillman Cancer Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Medical University of South Carolina (MUSC)

Recruiting

Charleston, South Carolina, United States, 29425

MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Oncology Consultants

Recruiting

Houston, Texas, United States, 77030

VCU Massey Cancer Center

Recruiting

Richmond, Virginia, United States, 23298

Tom Baker Cancer Centre (Alberta Health Services)

Recruiting

Calgary, Alberta, Canada, T3N 4N1

Cross Cancer Institute

Recruiting

Edmonton, Alberta, Canada, T6G 1Z2

Princess Margaret Cancer Center - University Health Network

Recruiting

Toronto, Ontario, Canada, M5G 2M9

McGill University Health Centre (MUHC)

Recruiting

Montreal, Quebec, Canada, H4A3J1

More Information

Sponsor

AVEO Pharmaceuticals, Inc.

Last update posted

Apr 9, 2026

Last verified

Apr, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by AVEO Pharmaceuticals, Inc. on 2026-04-09.