Assessment of Efficacy and Safety of Monalizumab Plus Cetuximab Compared to Placebo Plus Cetuximab in Recurrent or Metastatic Head and Neck Cancer

NCT04590963 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 3 other identifiers: D7310C000012024-511813-39-002019-004770-25
• Study Type: interventional
• Target: 370
• Locations: 22 countries
• Sites: 123

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

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

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS) in Human Papillomavirus (HPV)-Unrelated Analysis Set

  The OS is defined as time from the date of randomization until death due to any cause regardless of whether the participant withdraws from randomized therapy or receives another anti-cancer therapy (i.e. date of death or censoring - date of randomization + 1). The OS was analyzed using Kaplan-Meier technique. Statistical analysis was performed using P-value from a stratified log-rank test and hazard ratio (HR) and confidence intervals (CIs) from a stratified Cox proportional hazards model. Analyses were stratified on World Health Organization/ Eastern Cooperative Oncology Group performance status (WHO/ECOG PS) (0 or 1) and number of prior lines of therapy in recurrent or metastatic (R/M) setting (1 or 2).

  Baseline (-28 to -1) through 17.5 months (maximum observed duration)

Secondary Outcomes (11)

• Overall Survival in Full Analysis Set (FAS)

  Baseline (-28 to -1) through 17.5 months (maximum observed duration)

• Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator Assessment in HPV-unrelated Analysis Set

  Baseline (-28 to -1) through 17.5 months (maximum observed duration)

• Progression-Free Survival Per RECIST 1.1 by Investigator Assessment in FAS

  Baseline (-28 to -1) through 17.5 months (maximum observed duration)

• Percentage of Participants With Objective Response (OR) Per RECIST 1.1 in HPV-unrelated Analysis Set

  Baseline (-28 to -1) through 17.5 months (maximum observed duration)

• Percentage of Participants With OR Per RECIST 1.1 in FAS

  Baseline (-28 to -1) through 17.5 months (maximum observed duration)

Study Arms (2)

Monalizumab 750 mg Q2W + Cetuximab 400 mg/m^2

EXPERIMENTAL

Participants will receive intravenous (IV) monalizumab 750 mg every two weeks (Q2W) and IV cetuximab 400 mg/m\^2 initial dose followed by 250 mg/m\^2 every one week (Q1W) until disease progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Drug: Monalizumab; Drug: Cetuximab

Placebo Q2W + Cetuximab 400 mg/m^2

ACTIVE COMPARATOR

Participants will receieve IV placebo matched to monalizumab Q2W and IV cetuximab 400 mg/m\^2 initial dose followed by 250 mg/m\^2 Q1W until disease progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Drug: Cetuximab; Other: Placebo

Interventions

Monalizumab DRUG

Participants will receive IV infusion of monalizumab as stated in arm description.

Also known as: IPH2201

Monalizumab 750 mg Q2W + Cetuximab 400 mg/m^2

Cetuximab DRUG

Participants will receive IV infusion of cetuximab as stated in arm description.

Also known as: Erbitux

Monalizumab 750 mg Q2W + Cetuximab 400 mg/m^2; Placebo Q2W + Cetuximab 400 mg/m^2

Placebo OTHER

Participants will receive IV infusion of placebo as stated in arm description.

Placebo Q2W + Cetuximab 400 mg/m^2

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• AstraZeneca: lead
• Innate Pharma: collaborator

Study Sites (127)

Research Site

Tucson, Arizona, 85719, United States

Location

Research Site

Chicago, Illinois, 60612, United States

Location

Research Site

Westwood, Kansas, 66205, United States

Location

Research Site

Boston, Massachusetts, 02215, United States

Location

Research Site

Ann Arbor, Michigan, 48109, United States

Location

Research Site

Rochester, Minnesota, 55905, United States

Location

Research Site

St Louis, Missouri, 63110, United States

Location

Research Site

Las Vegas, Nevada, 89169, United States

Location

Research Site

New York, New York, 10029, United States

Location

Research Site

Charlotte, North Carolina, 28204, United States

Location

Research Site

Winston-Salem, North Carolina, 27103, United States

Location

Research Site

Columbus, Ohio, 43210, United States

Location

Research Site

Philadelphia, Pennsylvania, 19104, United States

Location

Research Site

Philadelphia, Pennsylvania, 19111, United States

Location

Research Site

Pittsburgh, Pennsylvania, 15232, United States

Location

Research Site

Dallas, Texas, 75246, United States

Location

Research Site

Houston, Texas, 77090, United States

Location

Research Site

CABA, 1426, Argentina

Location

Research Site

CABA, C1012AAR, Argentina

Location

Research Site

CABA, C1426ANZ, Argentina

Location

Research Site

Camperdown, 2050, Australia

Location

Research Site

Elizabeth Vale, 5112, Australia

Location

Research Site

Heidelberg, 3084, Australia

Location

Research Site

Melbourne, 3000, Australia

Location

Research Site

Linz, 4010, Austria

Location

Research Site

Brussels, 1200, Belgium

Location

Research Site

Leuven, 3000, Belgium

Location

Research Site

Namur, 5000, Belgium

Location

Research Site

Roeselare, 8800, Belgium

Location

Research Site

Belo Horizonte, 30110-022, Brazil

Location

Research Site

Porto Alegre, 90560-030, Brazil

Location

Research Site

Rio de Janeiro, 22271-110, Brazil

Location

Research Site

São Paulo, 01321-001, Brazil

Location

Research Site

São Paulo, 01327-001, Brazil

Location

Research Site

São Paulo, 01509-900, Brazil

Location

Research Site

São Paulo, 04543-000, Brazil

Location

Research Site

Panagyurishte, 4500, Bulgaria

Location

Research Site

Plovdiv, 4004, Bulgaria

Location

Research Site

Sofia, 1527, Bulgaria

Location

Research Site

Victoria, British Columbia, V8R 6V5, Canada

Location

Research Site

Hamilton, Ontario, L8V 5C2, Canada

Location

Research Site

Toronto, Ontario, M4N 3M5, Canada

Location

Research Site

Toronto, Ontario, M5G 2M9, Canada

Location

Research Site

Montreal, Quebec, H3T 1E2, Canada

Location

Research Site

Avignon, 84918, France

Location

Research Site

Bordeaux, 33000, France

Location

Research Site

Clermont-Ferrand, 63011, France

Location

Research Site

Dijon, 21079, France

Location

Research Site

Lyon, 69373, France

Location

Research Site

Marseille, 13005, France

Location

Research Site

Montpellier, 34298, France

Location

Research Site

Strasbourg, 67033, France

Location

Research Site

Berlin, 12203, Germany

Location

Research Site

Essen, 45122, Germany

Location

Research Site

Freiburg im Breisgau, 79106, Germany

Location

Research Site

Hanover, 30625, Germany

Location

Research Site

Leipzig, 04103, Germany

Location

Research Site

Ulm, 89081, Germany

Location

Research Site

Würzburg, 97070, Germany

Location

Research Site

Athens, 11528, Greece

Location

Research Site

Chaïdári, 124 62, Greece

Location

Research Site

Thessaloniki, 54645, Greece

Location

Research Site

Brescia, 25123, Italy

Location

Research Site

Candiolo, 10060, Italy

Location

Research Site

Florence, 50134, Italy

Location

Research Site

Milan, 20132, Italy

Location

Research Site

Milan, 20133, Italy

Location

Research Site

Modena, 41124, Italy

Location

Research Site

Naples, 80131, Italy

Location

Research Site

Padua, 35128, Italy

Location

Research Site

Chūōku, 104-0045, Japan

Location

Research Site

Fukuoka, 811-1395, Japan

Location

Research Site

Hiroshima, 734-8551, Japan

Location

Research Site

Isehara-shi, 259-1193, Japan

Location

Research Site

Kashiwa, 277-8577, Japan

Location

Research Site

Kobe, 650-0017, Japan

Location

Research Site

Kōtoku, 135-8550, Japan

Location

Research Site

Okayama, 700-8558, Japan

Location

Research Site

Sayama, 589-8511, Japan

Location

Research Site

Sunto-gun, 411-8777, Japan

Location

Research Site

Yokohama, 236-0004, Japan

Location

Research Site

Yokohama, 241-8515, Japan

Location

Research Site

Amsterdam, 1066 CX, Netherlands

Location

Research Site

Maastricht, 6229 HX, Netherlands

Location

Research Site

Nijmegen, 6525 GA, Netherlands

Location

Research Site

Manila, 1000, Philippines

Location

Research Site

Pasig, 1605, Philippines

Location

Research Site

Quezon City, 1112, Philippines

Location

Research Site

Bialystok, 15-027, Poland

Location

Research Site

Bydgoszcz, 85-796, Poland

Location

Research Site

Poznan, 61-866, Poland

Location

Research Site

Coimbra, 3000-075, Portugal

Location

Research Site

Porto, 4099-001, Portugal

Location

Research Site

Porto, 4200-319, Portugal

Location

Research Site

Vila Nova de Gaia, 4434-502, Portugal

Location

Research Site

Moscow, 115478, Russia

Location

Research Site

Moscow Region, 143081, Russia

Location

Research Site

Obninsk, 249036, Russia

Location

Research Site

Saint Petersburg, 191014, Russia

Location

Research Site

Saint Petersburg, 195271, Russia

Location

Research Site

Saint Petersburg, 197022, Russia

Location

Research Site

Saint Petersburg, 197758, Russia

Location

Research Site

Busan, 49267, South Korea

Location

Research Site

Cheongju-si, 28644, South Korea

Location

Research Site

Goyang-si, 10408, South Korea

Location

Research Site

Seongnam-si, 13620, South Korea

Location

Research Site

Seoul, 06351, South Korea

Location

Research Site

Seoul, 110-744, South Korea

Location

Research Site

Seoul, 138-736, South Korea

Location

Research Site

Barcelona, 08035, Spain

Location

Research Site

Madrid, 28007, Spain

Location

Research Site

Madrid, 28040, Spain

Location

Research Site

Madrid, 28041, Spain

Location

Research Site

Valencia, 46014, Spain

Location

Research Site

Basel, 4031, Switzerland

Location

Research Site

Bern, 3010, Switzerland

Location

Research Site

Lausanne, CH-1011, Switzerland

Location

Research Site

Changhua, 500, Taiwan

Location

Research Site

Taichung, 40447, Taiwan

Location

Research Site

Taichung, 40705, Taiwan

Location

Research Site

Tainan, 704, Taiwan

Location

Research Site

Taipei, 112, Taiwan

Location

Research Site

Taipei, 235, Taiwan

Location

Research Site

London, SW3 6JJ, United Kingdom

Location

Research Site

Manchester, M20 4BX, United Kingdom

Location

Research Site

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Research Site

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (1)

• Nowojewski A, Wheal A, Dott W, Ruscica D, Ghiorghiu S, Valastro B. Implementation of the Study Participant Feedback Questionnaire to understand participant experience in a phase 3 oncology clinical trial. BMJ Open. 2025 Oct 28;15(10):e094596. doi: 10.1136/bmjopen-2024-094596.

  PMID: 41151963 DERIVED

Related Links

• Redacted Statistical Analysis Plan
• Redacted Study Protocol
• Redacted CSR synopsis

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Laryngeal Diseases

Interventions

monalizumab; Cetuximab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Respiratory Tract Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Study enrolment was discontinued after the planned initial interim futility analysis (IA1) due to unlikelihood of achieving statistical significance for OS in the primary endpoint (HPV-unrelated). Therefore, symptoms, function, health-related quality of life (HRQoL), European Organization for Research and Treatment of Cancer (EORTC) scale/item score, pharmacokinetic (PK) parameters, immunogenicity, human leukocyte antigen E (HLA-E), and NKp46+ expression outcomes were not evaluated.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca Clinical Study Information Center

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Roger B Cohen, MD

  Abramson Cancer Center, Perelman Center for Advanced Medicine

  PRINCIPAL INVESTIGATOR

• Jérôme Fayette, MD

  Centre Leon Berard

  PRINCIPAL INVESTIGATOR

• Dario Ruscica, MD

  AstraZeneca, Cambridge, UK

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blinded study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel study. Participants will be randomized in a 2:1 ratio to monalizumab and cetuximab or placebo and cetuximab.

Study Record Dates

• First Submitted: September 23, 2020
• First Posted: October 19, 2020
• Study Start: October 2, 2020
• Primary Completion: May 11, 2022
• Study Completion (Estimated): September 24, 2026
• Last Updated: March 13, 2026
• Results First Posted: November 18, 2023

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of the timelines, please refer to the disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

IT (8); PH (3); CA (5); JP (12); ES (5); GB (4); CH (3); BE (4); NL (3); KR (7); AU (1); FR (8); DE (7); US (17); GR (3); TW (6); BU (3); PL (3); PT (4); AR (3); RU (7); BR (7)