A 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)
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| ClinicalTrials.gov Identifier: NCT06064877 |
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Recruitment Status :
Recruiting
First Posted : October 3, 2023
Last Update Posted : May 14, 2024
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Sponsor:
AVEO Pharmaceuticals, Inc.
Information provided by (Responsible Party):
AVEO Pharmaceuticals, Inc.
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Metastatic Head-and-neck Squamous-cell Carcinoma Recurrent Head and Neck Squamous Cell Carcinoma | Biological: Ficlatuzumab Biological: Cetuximab Other: Placebo | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 410 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Masking Description: | Double-Blind, Placebo-Controlled |
| Primary Purpose: | Treatment |
| Official Title: | 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) |
| Actual Study Start Date : | January 11, 2024 |
| Estimated Primary Completion Date : | August 2027 |
| Estimated Study Completion Date : | November 2027 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Head and neck squamous cell carcinoma
Drug Information
available for:
Cetuximab
| Arm | Intervention/treatment |
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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
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Biological: Ficlatuzumab
Ficlatuzumab (AV-299) is a humanized hepatocyte growth factor (HGF) inhibitory immunoglobulin G1 (IgG1) monoclonal antibody (mAb).
Other Name: AV-299 Biological: Cetuximab Cetuximab is an epidermal growth factor receptor (EGFR) antagonist.
Other Name: Erbitux |
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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
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Biological: Ficlatuzumab
Ficlatuzumab (AV-299) is a humanized hepatocyte growth factor (HGF) inhibitory immunoglobulin G1 (IgG1) monoclonal antibody (mAb).
Other Name: AV-299 Biological: Cetuximab Cetuximab is an epidermal growth factor receptor (EGFR) antagonist.
Other Name: Erbitux |
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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
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Biological: Cetuximab
Cetuximab is an epidermal growth factor receptor (EGFR) antagonist.
Other Name: Erbitux Other: Placebo Placebo for this study will be normal saline |
Primary Outcome Measures :
- 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) ]Overall survival (OS), defined as the time from the date of randomization to the date of death for any cause
Secondary Outcome Measures :
- To evaluate additional endpoints of efficacy for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC [ Time Frame: From Randomization until disease progression or death (Approximately 44 months) ]Progression-free survival (PFS), defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death from any cause, whichever occurs first
- To evaluate additional endpoints of efficacy for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC [ Time Frame: 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) ]Objective response rate (ORR), defined as the percentage of participants who have a complete response (CR) or a partial response (PR) per RECIST v1.1
- To evaluate additional endpoints of efficacy for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC [ Time Frame: 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) ]Duration of response (DOR), defined as the time from first documented evidence of a confirmed CR or PR per RECIST v1.1
- To compare the safety and tolerability of ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC [ Time Frame: From Screening until 30 days after last dose ]Number of times participants experience Adverse Events (AE) or abnormal laboratory values.
- To evaluate the pharmacokinetics (Pk) of ficlatuzumab and cetuximab [ Time Frame: From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months) ]Serum samples will be assessed for concentrations of ficlatuzumab and cetuximab
- To assess the immunogenicity of ficlatuzumab via antidrug antibodies (ADAs) [ Time Frame: From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months) ]Serum samples will be assessed for the presence of ADA to ficlatuzumab.
- To assess the immunogenicity of ficlatuzumab via neutralizing antibodies (nAB) [ Time Frame: From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months) ]Serum samples that test positive for the presence of ADA to ficlatuzumab will be further tested for the presence of nAB.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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 HPV-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
- 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 60 days 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/HGF analysis
Exclusion Criteria:
- History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational agent or cetuximab
- Known 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.
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Prior treatment with any other investigational drug or biologic agent before a washout has been completed (must be completed prior to randomization):
- 2 weeks (14 days) or 5 half-lives, whichever is shorter, for chemotherapeutic agents, small molecules, and checkpoint inhibitors
- 3 weeks (21 days) or 5 half-lives, whichever is shorter, for antibody-drug conjugates
- 4 weeks (28 days) for cell therapies
- 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)
- Female participants who are pregnant or breastfeeding
A full list of inclusion and exclusion criteria can be found in the protocol.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06064877
Contacts
| Contact: Clinical Trials Office | +1.857.400.0101 | clinical@aveooncology.com |
Locations
Show 19 study locations
Sponsors and Collaborators
AVEO Pharmaceuticals, Inc.
| Responsible Party: | AVEO Pharmaceuticals, Inc. |
| ClinicalTrials.gov Identifier: | NCT06064877 |
| Other Study ID Numbers: |
AV-299-23-301 |
| First Posted: | October 3, 2023 Key Record Dates |
| Last Update Posted: | May 14, 2024 |
| Last Verified: | May 2024 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by AVEO Pharmaceuticals, Inc.:
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Recurrent Metastatic HPV-negative Head and Neck Squamous Cell Carcinoma |
Additional relevant MeSH terms:
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Squamous Cell Carcinoma of Head and Neck Head and Neck Neoplasms Carcinoma Carcinoma, Squamous Cell Recurrence Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms |
Disease Attributes Pathologic Processes Neoplasms, Squamous Cell Neoplasms by Site Cetuximab Antineoplastic Agents, Immunological Antineoplastic Agents |