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Combining ficlatuzumab with cetuximab for advanced HPV-negative head and neck cancer

A Multicenter, Randomized, Double Blind, Placebo - Controlled, Phase 3 Study of Ficlatuzumab in Combination With Cetuximab in Participants With Recurrent or Metastatic (R/M) HPV -Negative Head and Neck Squamous Cell Carcinoma. (FIERCE-HN)

Phase 3 Interventional AVEO Pharmaceuticals, Inc. · NCT06064877

This study is testing if adding a new drug called ficlatuzumab to cetuximab can help people with advanced HPV-negative head and neck cancer live longer and feel better compared to just using cetuximab with a placebo.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment410 (estimated)
Ages18 Years and up
SexAll
SponsorAVEO Pharmaceuticals, Inc. Industry-sponsored
Drugs / interventionscetuximab, chemotherapy, radiation, ficlatuzumab
Locations112 sites (Gilbert, Arizona and 111 other locations)
Trial IDNCT06064877 on ClinicalTrials.gov

What this trial studies

This Phase 3 clinical trial aims to evaluate the efficacy and safety of ficlatuzumab in combination with cetuximab compared to a placebo plus cetuximab in patients with recurrent or metastatic HPV-negative head and neck squamous cell carcinoma. The study is multicenter, randomized, and double-blind, enrolling approximately 410 participants who have previously failed anti-PD-1/PD-L1 immune checkpoint inhibitors and platinum-based chemotherapy. Participants will be assigned to one of three arms to assess progression-free survival and overall survival outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with recurrent or metastatic HPV-negative head and neck squamous cell carcinoma who have failed prior therapies.

Not a fit: Patients with operable tumors or those who have not previously undergone anti-PD-1/PD-L1 therapy or platinum-based chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could improve survival rates for patients with advanced HPV-negative head and neck cancer.

How similar studies have performed: Previous studies have shown promising results with similar combinations in treating head and neck cancers, indicating potential for success.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Where this trial is running

Gilbert, Arizona and 111 other locations

+62 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Metastatic Head-and-neck Squamous-cell CarcinomaRecurrent Head and Neck Squamous Cell CarcinomaRecurrentMetastaticHPV-negativeHead and NeckSquamous Cell Carcinoma
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.