Clinical trial NCT04590963: Assessment of Efficacy and Safety of Monalizumab Plus Cetuximab Compared to Placebo Plus Cetuximab in Recurrent or Metastatic Head and Neck Cancer
Official title: A Phase 3 Randomized, Double-blind, Multicenter, Global Study of Monalizumab or Placebo in Combination With Cetuximab in Participants With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Previously Treated With an Immune Checkpoint Inhibitor
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Squamous Cell Carcinoma of the Head and Neck
Keywords: head and neck cancer
Squamous Cell Carcinoma of the Head and Neck
monalizumab
cetuximab
Erbitux
oral cavity
larynx
pharynx
natural killer
oropharynx
hypopharynx
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Innate Pharma
First posted: 2020-10-19
Enrollment: 370
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel study. Participants will be randomized in a 2:1 ratio to monalizumab and cetuximab or placebo and cetuximab.
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, multicenter, global Phase 3 study to assess the efficacy and safety of monalizumab and cetuximab, compared to placebo and cetuximab, in Participants with recurrent or metastatic head and neck cancer.

Detailed description: Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) who had prior immune checkpoint inhibitor and platinum-based chemotherapy treatment will be randomized in a 2:1 ratio to monalizumab and cetuximab or placebo and cetuximab. Efficacy and safety assessments will be performed periodically from the time of enrollment and throughout the study. Participants in all arms will continue therapy until progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. All Participants will be followed for survival after progression is confirmed.

Eligibility criteria: Inclusion Criteria:

* Are aged 18 years and over
* Recurrent or metastatic squamous cell carcinoma of the SCCHN, oral cavity, oropharynx, hypopharynx, or larynx which has progressed on or after previous systemic cancer therapy and is not amenable to curative therapy
* Received prior treatment using a programmed cell death ligand-1 (PD-L1) inhibitor
* Prior platinum failure
* Received 1 or 2 prior systemic regimens for recurrent or metastatic SCCHN
* Has measurable disease per RECIST 1.1
* A fresh or recently acquired tumor tissue for the purpose of biomarker testing
* World Health Organization (WHO)/ Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

Exclusion Criteria:

* Head and neck cancer of any primary anatomic location in the head and neck not specified in the inclusion criteria, including participants with SCCHN of unknown primary or non-squamous histologies
* Had prior cetuximab therapy (unless it was administered in curative locally advanced setting with radiotherapy and no disease progression for at least 6 months following the last cetuximab dose)
* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis
* Any concurrent anticancer treatment, except for hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy)

Primary outcomes:
measure: Overall Survival (OS) in Human Papillomavirus (HPV)-Unrelated Analysis Set
timeFrame: Baseline (-28 to -1) through 17.5 months (maximum observed duration)
Secondary outcomes:
measure: Overall Survival in Full Analysis Set (FAS)
timeFrame: Baseline (-28 to -1) through 17.5 months (maximum observed duration)
measure: Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator Assessment in HPV-unrelated Analysis Set
timeFrame: Baseline (-28 to -1) through 17.5 months (maximum observed duration)
measure: Progression-Free Survival Per RECIST 1.1 by Investigator Assessment in FAS
timeFrame: Baseline (-28 to -1) through 17.5 months (maximum observed duration)
measure: Percentage of Participants With Objective Response (OR) Per RECIST 1.1 in HPV-unrelated Analysis Set
timeFrame: Baseline (-28 to -1) through 17.5 months (maximum observed duration)
measure: Percentage of Participants With OR Per RECIST 1.1 in FAS
timeFrame: Baseline (-28 to -1) through 17.5 months (maximum observed duration)
measure: Duration of Response (DoR) Per RECIST 1.1 in HPV-unrelated Analysis Set
timeFrame: Baseline (-28 to -1) through 17.5 months (maximum observed duration)
measure: Duration of Response Per RECIST 1.1 in FAS
timeFrame: Baseline (-28 to -1) through 17.5 months (maximum observed duration)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Day 1 through 21.4 months (maximum observed duration)
measure: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
timeFrame: Day 1 through 21.4 months (maximum observed duration)
measure: Number of Participants With Abnormal Vital Signs Reported as TEAEs
timeFrame: Day 1 through 21.4 months (maximum observed duration)
measure: Number of Participants With Electrocardiograms (ECGs) Reported as TEAEs
timeFrame: Day 1 through 21.4 months (maximum observed duration)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Research Site
state: Arizona
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Westwood
country: United States
facility: Research Site
state: Kansas
city: Boston
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state: Massachusetts
city: Ann Arbor
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state: Michigan
city: Rochester
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state: Minnesota
city: Saint Louis
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city: Caba
country: Argentina
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country: Argentina
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country: Argentina
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country: Australia
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country: Australia
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city: Linz
country: Austria
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city: Bruxelles
country: Belgium
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country: Belgium
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city: Namur
country: Belgium
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country: Belgium
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country: Brazil
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country: Brazil
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country: Brazil
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country: Brazil
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country: Brazil
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country: Bulgaria
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country: Bulgaria
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country: Bulgaria
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city: Hamilton
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city: Avignon
country: France
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country: France
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city: Clermont Ferrand cedex 01
country: France
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country: France
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country: France
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country: France
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city: Montpellier Cedex 05
country: France
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country: France
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city: Berlin
country: Germany
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country: Germany
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country: Germany
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country: Germany
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city: Leipzig
country: Germany
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country: Germany
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country: Germany
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city: Athens
country: Greece
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city: Chaidari
country: Greece
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city: Thessaloniki
country: Greece
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city: Brescia
country: Italy
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city: Candiolo
country: Italy
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city: Firenze
country: Italy
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country: Italy
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country: Italy
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country: Italy
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country: Italy
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city: Padova
country: Italy
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city: Chuo-ku
country: Japan
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city: Fukuoka-shi
country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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city: Okayama
country: Japan
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country: Japan
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country: Japan
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city: Yokohama-shi
country: Japan
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city: Yokohama-shi
country: Japan
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city: Busan
country: Korea, Republic of
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city: Cheongju-si
country: Korea, Republic of
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city: Goyang-si
country: Korea, Republic of
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city: Seongnam-si
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Amsterdam
country: Netherlands
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city: Maastricht
country: Netherlands
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city: Nijmegen
country: Netherlands
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city: Manila
country: Philippines
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city: Pasig City
country: Philippines
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city: Quezon City
country: Philippines
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city: Białystok
country: Poland
facility: Research Site
city: Bydgoszcz
country: Poland
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city: Poznan
country: Poland
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city: Coimbra
country: Portugal
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city: Porto
country: Portugal
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city: Porto
country: Portugal
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city: Vila Nova de Gaia
country: Portugal
facility: Research Site
city: Moscow region
country: Russian Federation
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city: Moscow
country: Russian Federation
facility: Research Site
city: Obninsk
country: Russian Federation
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city: Saint Petersburg
country: Russian Federation
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city: Saint-Petersburg
country: Russian Federation
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city: Saint-Petersburg
country: Russian Federation
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city: St.Petersburg
country: Russian Federation
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city: Barcelona
country: Spain
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city: Madrid
country: Spain
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city: Madrid
country: Spain
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city: Madrid
country: Spain
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country: Spain
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city: Basel
country: Switzerland
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city: Bern
country: Switzerland
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city: Lausanne
country: Switzerland
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city: Changhua
country: Taiwan
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city: Taichung
country: Taiwan
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city: Taichung
country: Taiwan
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city: Tainan City
country: Taiwan
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city: Taipei
country: Taiwan
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city: Taipei
country: Taiwan
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Research Site
city: Sutton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Abramson Cancer Center, Perelman Center for Advanced Medicine
name: Roger B Cohen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Leon Berard
name: Jérôme Fayette, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca, Cambridge, UK
name: Dario Ruscica, MD
role: STUDY_DIRECTOR
References: