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Overview Study details Eligibility Things to know Research Study plan

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

PHASE3RECRUITING

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.

Study details:

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.

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

Study type

TREATMENT

Phase

PHASE3

Study ID

NCT06064877

Intervention or treatment

BIOLOGICAL: Ficlatuzumab

BIOLOGICAL: Cetuximab

OTHER: Placebo

Conditions

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

Condition: Metastatic Head-and-neck Squamous-cell Carcinoma, Recurrent Head and Neck Squamous Cell Carcinoma
BIOLOGICAL: Ficlatuzumab and other drugs
Kogarah, New South Wales, Australia and more
Sponsor: AVEO Pharmaceuticals, Inc.

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Research sites nearby

Closest Location:

St George Hospital

Select from list below to view details:

St George Hospital
Kogarah, New South Wales, Australia
St. Vincent's Hospital
Sydney, New South Wales, Australia
Princess Alexandra Hospital
Brisbane, Queensland, Australia
St. John of God Murdoch Hospital
Murdoch, Western Australia, Australia

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Who is running the clinical trial?

API

AVEO Pharmaceuticals, Inc.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
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	Biological: Ficlatuzumab, Biological: Cetuximab
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	Biological: Ficlatuzumab, Biological: Cetuximab
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	Biological: Cetuximab, Other: Placebo

What is the study measuring?

Primary Outcome

Measure	Description	Time Frame
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)	Overall survival (OS), defined as the time from the date of randomization to the date of death for any cause	From Randomization until death from any cause (Approximately 44 months)

Secondary Outcome

Measure	Description	Time Frame
To evaluate progression-free survival (PFS) for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC	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	From Randomization until disease progression or death (Approximately 44 months)
To evaluate additional objective response rate for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC	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	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)
To evaluate disease control rate (DCR) for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC	Disease control rate (DCR), defined for participants who have achieved a CR, PR or stable disease for at least 8 weeks per RECIST v1.1	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)
To evaluate duration of response (DOR) for ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC	Duration of response (DOR), defined as the time from first documented evidence of a confirmed CR or PR per RECIST v1.1	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)
To compare the safety and tolerability of ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC	Number of times participants experience Adverse Events (AE) or abnormal laboratory values.	From Screening until 30 days after last dose
To evaluate the pharmacokinetics (PK) of ficlatuzumab	Serum samples will be assessed for concentrations of ficlatuzumab	From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months)
To assess the immunogenicity of ficlatuzumab via antidrug antibodies (ADAs)	Serum samples will be assessed for the presence of ADA to ficlatuzumab.	From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months)
To assess the immunogenicity of ficlatuzumab via neutralizing antibodies (nAB)	Serum samples that test positive for the presence of ADA to ficlatuzumab will be further tested for the presence of nAB.	From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months)
To evaluate the quality of life (QOL) of ficlatuzumab plus cetuximab vs placebo plus cetuximab in participants with R/M HNSCC	Change from baseline in overall health status and time to clinically meaningful deterioration based on scoring of standardized participant questionnaires	From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months)

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References

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

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