Sponsor: AVEO Pharmaceuticals, Inc. (industry)
Phase: 3
Start date: Jan. 11, 2024
Planned enrollment: 410
Ficlatuzumab (AV-299) is an investigational antibody studied as a cancer treatment, usually in combination with other drugs. Human trial results are available, but a clinical benefit from adding ficlatuzumab has not been established. A phase 3 trial is evaluating it with cetuximab in HPV-negative recurrent or metastatic head and neck cancer. (pmc.ncbi.nlm.nih.gov)
Ficlatuzumab binds and neutralizes hepatocyte growth factor (HGF), preventing HGF from activating its receptor, MET (also called c-MET). In head and neck cancer, this approach is being tested alongside cetuximab, which targets a different signaling pathway. (pmc.ncbi.nlm.nih.gov)
Reported adverse events include edema and low blood albumin. In a randomized lung-cancer trial, peripheral edema and low albumin were more frequent with ficlatuzumab plus gefitinib than with gefitinib alone. Serious events have also been reported in early trials; risks can vary with the accompanying treatment and patient population. (sciencedirect.com)
Last updated: Sep 2026
Goal: Determine whether adding ficlatuzumab to cetuximab improves survival in recurrent or metastatic HPV-negative head and neck squamous cell carcinoma (HNSCC) after prior immunotherapy and platinum chemotherapy, while assessing safety.
Patients: Adults with inoperable, incurable recurrent or metastatic HPV-negative HNSCC, measurable disease, ECOG performance status 0–1, and prior failure or intolerance of both anti-PD-1/PD-L1 therapy and platinum chemotherapy. Patients with oropharyngeal cancer must have documented p16-negative status. Key exclusions include more than two prior anticancer lines, prior cetuximab or another EGFR inhibitor for recurrent or metastatic disease, and uncontrolled brain metastases.
Design: Multicenter, randomized, double-blind, placebo-controlled study comparing two ficlatuzumab dose levels plus cetuximab with placebo plus cetuximab across three arms.
Treatments: Patients receive intravenous ficlatuzumab at one of two dose levels, or matched placebo, together with intravenous cetuximab on days 1 and 15 of each 28-day cycle. Ficlatuzumab is an investigational antibody that neutralizes hepatocyte growth factor, preventing activation of its receptor MET. In a small, noncomparative phase 2 HNSCC study, ficlatuzumab plus cetuximab produced responses in 6 of 32 evaluable patients, including 6 of 16 in an exploratory HPV-negative subgroup; these results do not establish benefit over cetuximab alone. Cetuximab is an EGFR-targeting antibody used in HNSCC.
Outcomes: The primary endpoint is overall survival from randomization. Secondary endpoints include RECIST 1.1 progression-free survival, objective response rate, disease control rate, duration of response, adverse events and laboratory abnormalities, ficlatuzumab pharmacokinetics and immunogenicity, and patient-reported quality of life.
Burden on patient: Moderate burden: patients attend twice-monthly visits for intravenous treatment and undergo imaging every 8 weeks during year 1, every 12 weeks during years 2 and 3, and every 6 months thereafter. Additional blood sampling for pharmacokinetics and antidrug antibodies, questionnaires, and submission of archived tumor tissue are required; a fresh biopsy may be needed if archived tissue is unavailable.
Last updated: Sep 2026
Caution: ClinicalTrials.gov appears to have newer eligibility criteria than the version saved here. Review the current criteria in ClinicalTrials.gov.
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.
Kogarah, New South Wales, 2217, Australia
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Status: Recruiting
Sydney, New South Wales, 2010, Australia
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Brisbane, Queensland, 4102, Australia
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Murdoch, Western Australia, 6150, Australia
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Liège, 4000, Belgium
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Namur, B5000, Belgium
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Sint-Niklaas, 9100, Belgium
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Status: Recruiting
Edmonton, Alberta, T6G 1Z2, Canada
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Status: Recruiting
Calgary, Alberta, T3N 4N1, Canada
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Status: Recruiting
Toronto, Ontario, M5G 2M9, Canada
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Status: Recruiting
Montreal, Quebec, H4A3J1, Canada
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Status: Recruiting
Prague, 13400, Czechia
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Status: Recruiting
Brno, 60200, Czechia
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Status: Recruiting
Prague, Czechia
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Status: Recruiting
Brno, 65653, Czechia
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Status: Recruiting
Marseille, 13005, France
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Status: Recruiting
Lyon, 69008, France
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Status: Recruiting
Plérin, 22190, France
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Status: Recruiting
Paris, 75248, France
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Status: Recruiting
Villejuif, 94805, France
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Status: Recruiting
Chambray-lès-Tours, 37170, France
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Status: Recruiting
Berlin, 12200, Germany
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Status: Recruiting
Munich, 81377, Germany
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Status: Recruiting
Freiburg im Breisgau, 79106, Germany
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Status: Recruiting
Nyíregyháza, 4400, Hungary
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Status: Recruiting
Pécs, 7624, Hungary
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Status: Recruiting
Florence, 51134, Italy
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Status: Recruiting
Novara, 28100, Italy
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Status: Recruiting
Milan, 20133, Italy
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Status: Recruiting
Pavia, 27100, Italy
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Status: Recruiting
Milan, 20089, Italy
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Status: Recruiting
Bologna, 40139, Italy
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Status: Recruiting
Milan, 20132, Italy
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Status: Recruiting
Padua, 35128, Italy
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Status: Recruiting
Pavia, 27100, Italy
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Status: Recruiting
Nijmegen, 6525, Netherlands
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Status: Recruiting
Bydgoszcz, 85-796, Poland
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Status: Recruiting
Gliwice, 44-100, Poland
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Status: Recruiting
Floreşti, 407280, Romania
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Status: Recruiting
Cluj-Napoca, 400641, Romania
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Status: Recruiting
Kamenitz, Serbia
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Status: Recruiting
Belgrade, Serbia
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Status: Recruiting
Kragujevac, Serbia
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Status: Recruiting
Suwon, 16499, South Korea
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Status: Recruiting
Daegu, 42601, South Korea
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Status: Recruiting
Seoul, 02841, South Korea
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Status: Recruiting
Seoul, 06351, South Korea
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Status: Recruiting
Seoul, 03080, South Korea
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Status: Recruiting
Seoul, 03722, South Korea
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Status: Recruiting
Seoul, 03312, South Korea
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Status: Recruiting
Madrid, 28051, Spain
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Status: Recruiting
Valencia, Spain
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Status: Recruiting
Málaga, 29004, Spain
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Status: Recruiting
Madrid, 28046, Spain
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Status: Recruiting
Alicante, 03293, Spain
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Status: Recruiting
Madrid, Spain
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Status: Recruiting
Cadiz, 11407, Spain
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Status: Recruiting
Barcelona, 08908, Spain
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Status: Recruiting
Badalona, 08907, Spain
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Status: Recruiting
Barcelona, 08017, Spain
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Status: Recruiting
Barcelona, Spain
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Status: Recruiting
Kaohsiung City, 833401, Taiwan
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Status: Recruiting
Taoyuan District, 33305, Taiwan
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Status: Recruiting
Changhua, 500, Taiwan
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Status: Recruiting
Taichung, 40447, Taiwan
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Status: Recruiting
Taipei, 112201, Taiwan
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Status: Recruiting
Nottingham, NG5 1PB, United Kingdom
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Status: Recruiting
Aberdeen, AB25 2ZN, United Kingdom
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Status: Recruiting
London, W1G 6AD, United Kingdom
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Status: Recruiting
Sutton, SM2 5PT, United Kingdom
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Status: Recruiting
London, SW3 6JJ, United Kingdom
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Status: Recruiting
Gilbert, Arizona, 85212, United States
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Status: Recruiting
Tucson, Arizona, 85719, United States
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Status: Recruiting
Los Angeles, California, 90024, United States
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Status: Recruiting
New Haven, Connecticut, 06511, United States
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Status: Recruiting
Washington D.C., District of Columbia, 20052-0042, United States
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Status: Recruiting
Orlando, Florida, 32804, United States
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Status: Recruiting
Tampa, Florida, 33612, United States
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Status: Recruiting
Atlanta, Georgia, 30308, United States
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Status: Recruiting
Chicago, Illinois, 60612, United States
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Status: Recruiting
Westwood, Kansas, 66205, United States
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Status: Recruiting
Baton Rouge, Louisiana, 70809, United States
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Status: Recruiting
South Portland, Maine, 04106, United States
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Status: Recruiting
Baltimore, Maryland, 21201, United States
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Status: Recruiting
Boston, Massachusetts, 02215, United States
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Status: Recruiting
Boston, Massachusetts, 02114, United States
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Status: Recruiting
St Louis, Missouri, 63110, United States
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Status: Recruiting
New York, New York, 10065, United States
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Status: Recruiting
Lake Success, New York, 10042, United States
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Status: Recruiting
Columbus, Ohio, 43210, United States
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Status: Recruiting
Philadelphia, Pennsylvania, 19111, United States
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Status: Recruiting
Pittsburgh, Pennsylvania, 15232, United States
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Status: Recruiting
Charleston, South Carolina, 29425, United States
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Status: Recruiting
Houston, Texas, 77030, United States
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Status: Recruiting
Houston, Texas, 77030, United States
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Status: Recruiting
Richmond, Virginia, 23298, United States
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Status: Recruiting
Budapest, 1122, Hungary
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Status: Not yet recruiting
Panagyurishte, 4500, Bulgaria
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Status: Withdrawn
Ottawa, Ontario, K1H 8L6, Canada
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Status: Withdrawn
Olomouc, 77900, Czechia
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Status: Withdrawn
Brest, 29200, France
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Status: Withdrawn
Győr, 9024, Hungary
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Status: Withdrawn
Salgótarján, 3100, Hungary
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Status: Withdrawn
Roma, 00168, Italy
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Status: Withdrawn
Amsterdam, 1066, Netherlands
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Status: Withdrawn
Santander, Spain
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Status: Withdrawn
Tainan, 704017, Taiwan
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Status: Withdrawn
Taipei, 100, Taiwan
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Status: Withdrawn
Torquay, TQ2 7AA, United Kingdom
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Status: Withdrawn
The Bronx, New York, 10461, United States
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Status: Withdrawn
Cincinnati, Ohio, 45219, United States
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Status: Withdrawn
Milwaukee, Wisconsin, 53202, United States
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Status: TERMINATED