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

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)

Overview

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.

Detailed description

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.

Interventions

• Biological Ficlatuzumab
  Ficlatuzumab (AV-299) is a humanized hepatocyte growth factor (HGF) inhibitory immunoglobulin G1 (IgG1) monoclonal antibody (mAb).
• Biological Cetuximab
  Cetuximab is an epidermal growth factor receptor (EGFR) antagonist.
• 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)]

Secondary outcome measures (9)

• To evaluate progression-free survival (PFS) 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)]
• To evaluate additional objective response rate 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)]
• To evaluate disease control rate (DCR) 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)]
• To evaluate duration of response (DOR) 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)]
• 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]
• To evaluate the pharmacokinetics (PK) of ficlatuzumab [Time frame: 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) [Time frame: 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) [Time frame: 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 [Time frame: From Baseline (Cycle 1 Day 1 pre-dose) until End of Treatment (Approximately 44 months)]

Eligibility 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):

• 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
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 28 centers

• Banner MD Anderson Cancer Center — Gilbert
• The University of Arizona Cancer Center — Tucson
• University of California Los Angeles — Los Angeles
• Yale School of Medicine - Smilow Cancer Hospital — New Haven
• The George Washington University — Washington D.C.
• AdventHealth Medical Group Oncology & Hematology at Orlando — Orlando
• Moffitt Cancer Center — Tampa
• Emory University — Atlanta
• … and 20 more centers

Spain · 12 centers

Center list to be confirmed — check the primary protocol.

Italy · 10 centers

• IRCCS Istituto Scienze Neurologiche — Bologna
• AOU Careggi — Florence
• IRCCS Istituto Clinico Humanitas - Cancer center — Milan
• IRCCS Ospedale San Raffaele Milano — Milan
• Fondazione IRCCS - Istituto Nazionale Tumori - Oncologia — Milan
• Azienda Ospedaliera Universitaria Maggiore Della Carita Novara — Novara
• Istituto Oncologico Veneto — Padua
• IRCCS - ICS Maugeri — Pavia
• … and 2 more centers

France · 7 centers

• Clinique Pasteur - Lanroze- Centre Finistérien de Radiothérapie et d'Oncologie — Brest
• Pôle Santé Léonard de Vinci — Chambray-lès-Tours
• Centre Léon Bérard — Lyon
• Assistance Publique Hopitaux de Marseille (APHM)-Hôpital La Timone — Marseille
• Institut Curie — Paris
• Hôpital Privé des Côtes d'Armor — Plérin
• Institut Gustave Roussy — Villejuif

South Korea · 7 centers

Center list to be confirmed — check the primary protocol.

Taiwan · 7 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 6 centers

Center list to be confirmed — check the primary protocol.

Canada · 5 centers

• Tom Baker Cancer Centre (Alberta Health Services) — Calgary
• Cross Cancer Institute — Edmonton
• The Ottawa Hospital Cancer Centre — Ottawa
• Princess Margaret Cancer Center - University Health Network — Toronto
• McGill University Health Centre (MUHC) — Montreal

Czechia · 5 centers

• Fakultni nemocnice Brno — Brno
• Masaryk Memorial Cancer Institute — Brno
• Fakultni Nemocnice Olomouc — Olomouc
• Fakultni Nemocnice Kralovske Vinohrady — Prague
• Fakultni nemocnice Bulovka — Prague

Hungary · 5 centers

• Orszagos Onkologiai Intezet — Budapest
• Petz Aladar Country Teaching Hospital — Győr
• Josa Andras Oktatokorhaz — Nyíregyháza
• University of Pecs - Oncology — Pécs
• Szent Lázár Megyei Kórház — Salgótarján

Australia · 4 centers

• St George Hospital — Kogarah
• St. Vincent's Hospital — Sydney
• Princess Alexandra Hospital — Brisbane
• St. John of God Murdoch Hospital — Murdoch

Belgium · 3 centers

• CHU Liège — Liège
• CHU Universite Catholique de Louvain — Namur
• Vitaz-Sint-Niklaas Moerland — Sint-Niklaas

Germany · 3 centers

• Charite-Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK) - Medizinische Klinik — Berlin
• UNIVERSITÄTSKLINIKUM FREIBURG, Klinik für Innere Medizin I, Schwerpunkt Hämatologie, Onkol — Freiburg im Breisgau
• Ludwig-Maximilians University — Munich

Serbia · 3 centers

• Institute of Oncology and Radiology of Serbia — Belgrade
• Institute for Oncology Vojvodina — Kamenitz
• University Clinical Center Kragujevac — Kragujevac

Netherlands · 2 centers

• Antoni van Leeuwenhoek — Amsterdam
• Radboud University Medical Center — Nijmegen

Poland · 2 centers

• Centrum Onkologii im. prof. F. Lukaszczyka w Bydgoszczy — Bydgoszcz
• National Research Institute of Oncology — Gliwice

Romania · 2 centers

• Medisprof Cancer Center — Cluj-Napoca
• Centrul radioterapie Amethyst Cluj-Napoca — Floreşti

Bulgaria · 1 center

• University Hospital — Panagyurishte

Identifiers

NCT: NCT06064877 · AV-299-23-301

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗