A Phase 3 Study to Evaluate Petosemtamab Compared With Investigator's Choice Monotherapy in Previously Treated Head and Neck Squamous Cell Carcinoma Patients

NCT ID: NCT06496178

Last Updated: 2026-01-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

500 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-06-25

Study Completion Date

2029-03-31

Brief Summary

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This is a phase 3 open-label, randomized, controlled, multicenter study to compare petosemtamab vs investigator's choice monotherapy in HNSCC patients for the second- and third-line treatment of incurable metastatic/recurrent disease.

Detailed Description

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This is a phase 3 open-label, randomized, controlled, multicenter study to compare petosemtamab vs investigator's choice monotherapy in HNSCC patients for the second- and third-line treatment of incurable metastatic/recurrent disease. HNSCC patients must have progressive disease (PD) on or after anti-PD-1 therapy and platinum-containing therapy. Patients treated with platinum-containing therapy only in the adjuvant setting, or in the context of multimodal therapy for locally advanced disease, should have PD within 6 months of the last dose of platinum-containing therapy.

Conditions

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Head and Neck Squamous Cell Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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MCLA-158

Group Type EXPERIMENTAL

Petosemtamab

Intervention Type DRUG

MCLA-158

Investigator's Choice

Group Type ACTIVE_COMPARATOR

Investigator's Choice

Intervention Type DRUG

Cetuximab

Investigator's Choice

Intervention Type DRUG

Methotrexate

Investigator's Choice

Intervention Type DRUG

Docetaxel

Interventions

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Petosemtamab

MCLA-158

Intervention Type DRUG

Investigator's Choice

Cetuximab

Intervention Type DRUG

Investigator's Choice

Methotrexate

Intervention Type DRUG

Investigator's Choice

Docetaxel

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Signed ICF before initiation of any study procedures.
* Age ≥ 18 years at signing of ICF.
* Histologically previously confirmed HNSCC with evidence of metastatic or locally advanced disease not amenable to standard therapy with curative intent.
* HNSCC patients progressed on or after anti-PD-1 therapy and platinum-containing therapy.
* The eligible HNSCC primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.
* Documentation of p16 status (positive or negative) by local laboratory IHC for patients with primary oropharyngeal cancer.
* A baseline new tumor sample unless the patient has an available tumor sample as an FFPE block with sufficient material.
* Measurable disease as defined by RECIST v1.1 by radiologic methods.
* ECOG PS of 0 or 1
* Life expectancy ≥ 12 weeks, as per investigator
* Adequate organ function (as per protocol)

Exclusion Criteria

* Central nervous system metastases that are untreated or symptomatic, or require radiation, surgery, or continued steroid therapy to control symptoms within 14 days of study entry.
* Known leptomeningeal involvement
* Any systemic anticancer therapy within 4 weeks of the first dose of study treatment.
* Major surgery or radiotherapy within 3 weeks of the first dose of study treatment.
* Persistent Grade \>1 clinically significant toxicities related to prior antineoplastic therapies
* History of hypersensitivity reaction to any of the excipients of treatment required for this study.
* Unstable angina; history of congestive heart failure of Class II-IV New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment or history of myocardial infarction within 6 months of study entry
* History of prior malignancies with the exception of excised cervical intraepithelial neoplasia or nonmelanoma skin cancer, or curatively treated cancer deemed at low risk for recurrence with no evidence of disease
* Current dyspnea at rest of any origin, or other diseases requiring continuous oxygen therapy
* Current serious illness or medical conditions including, but not limited to, uncontrolled active infection, clinically significant pulmonary, metabolic or psychiatric disorders
* Patients with known infectious diseases (as per protocol)
* Pregnant or breastfeeding patients
* Patient has a primary tumor site of nasopharynx (any histology).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merus N.V.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Site 160

Mobile, Alabama, United States

Site Status RECRUITING

Site 102

Prescott, Arizona, United States

Site Status COMPLETED

Site 125

Scottsdale, Arizona, United States

Site Status RECRUITING

Site 82

Duarte, California, United States

Site Status RECRUITING

Site 25

La Jolla, California, United States

Site Status RECRUITING

Site 173

Orange, California, United States

Site Status RECRUITING

Site 28

Palo Alto, California, United States

Site Status RECRUITING

Site 127

Sacramento, California, United States

Site Status RECRUITING

Site 46

San Francisco, California, United States

Site Status RECRUITING

Site 130

Lone Tree, Colorado, United States

Site Status RECRUITING

Site 104

Washington D.C., District of Columbia, United States

Site Status RECRUITING

Site 12

Fort Myers, Florida, United States

Site Status RECRUITING

Site 123

Jacksonville, Florida, United States

Site Status RECRUITING

Site 9

Orlando, Florida, United States

Site Status RECRUITING

Site 138

Temple Terrace, Florida, United States

Site Status RECRUITING

Site 187

Atlanta, Georgia, United States

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Site 152

Chicago, Illinois, United States

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Site 68

Chicago, Illinois, United States

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Site 31

Indianapolis, Indiana, United States

Site Status RECRUITING

Site 8

Louisville, Kentucky, United States

Site Status RECRUITING

Site 40

Baton Rouge, Louisiana, United States

Site Status RECRUITING

Site 100

New Orleans, Louisiana, United States

Site Status RECRUITING

Site 153

Columbia, Maryland, United States

Site Status RECRUITING

Site 77

Boston, Massachusetts, United States

Site Status RECRUITING

Site 103

Ann Arbor, Michigan, United States

Site Status RECRUITING

Site 5

Detroit, Michigan, United States

Site Status RECRUITING

Site 49

Maple Grove, Minnesota, United States

Site Status RECRUITING

Site 124

Rochester, Minnesota, United States

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Site 18

St Louis, Missouri, United States

Site Status RECRUITING

Site 86

Hackensack, New Jersey, United States

Site Status RECRUITING

Site 15

Albuquerque, New Mexico, United States

Site Status RECRUITING

Site 24

New York, New York, United States

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Site 98

Chapel Hill, North Carolina, United States

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Site 122

Durham, North Carolina, United States

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Site 23

Cincinnati, Ohio, United States

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Site 87

Cleveland, Ohio, United States

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Site 32

Columbus, Ohio, United States

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Site 26

Portland, Oregon, United States

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Site 151

Bensalem, Pennsylvania, United States

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Site 158

Philadelphia, Pennsylvania, United States

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Site 159

Philadelphia, Pennsylvania, United States

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Site 50

Charleston, South Carolina, United States

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Site 60

Chattanooga, Tennessee, United States

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Site 54

Memphis, Tennessee, United States

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Site 59

Nashville, Tennessee, United States

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Site 67

Nashville, Tennessee, United States

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Site 55

Denison, Texas, United States

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Site 34

El Paso, Texas, United States

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Site 51

Houston, Texas, United States

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Site 7

Houston, Texas, United States

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Site 94

Pearland, Texas, United States

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Site 4

Salt Lake City, Utah, United States

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Site 10

Blacksburg, Virginia, United States

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Site 22

Charlottesville, Virginia, United States

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Site 156

Winchester, Virginia, United States

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Site 163

Seattle, Washington, United States

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Site 6

Spokane, Washington, United States

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Site 37

Buenos Aires, , Argentina

Site Status WITHDRAWN

Site 80

Buenos Aires, , Argentina

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Site 58

Caba, , Argentina

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Site 193

CABA, , Argentina

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Site 45

Córdoba, , Argentina

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Site 110

Rosario, , Argentina

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Site 57

Viedma, , Argentina

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Site 3

Darlinghurst, , Australia

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Site 170

Herston, , Australia

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Site 38

Melbourne, , Australia

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Site 30

Nedlands, , Australia

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Site 11

Saint Leonards, , Australia

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Site 73

Sydney, , Australia

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Site 129

Brussels, , Belgium

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Site 56

Brussels, , Belgium

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Site 92

Ghent, , Belgium

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Site 72

Leuven, , Belgium

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Site 108

Liège, , Belgium

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Site 69

Namur, , Belgium

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Site 154

Brasília, , Brazil

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Site 145

Porto Alegre, , Brazil

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Site 150

Porto Alegre, , Brazil

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Site 146

Recife, , Brazil

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Site 155

Rio de Janeiro, , Brazil

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Site 148

Rio de Janeiro, , Brazil

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Site 147

São Paulo, , Brazil

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Site 144

São Paulo, , Brazil

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Site 172

Montreal, , Canada

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Site 16

Providencia, , Chile

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Site 20

Recoleta, , Chile

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Site 27

Santiago, , Chile

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Site 21

Santiago, , Chile

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Site 188

Nový Jičín, , Czechia

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Site 105

Bordeaux, , France

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Site 162

Le Mans, , France

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Site 149

Lille, , France

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Site 118

Lyon, , France

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Site 115

Marseille, , France

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Site 106

Montpellier, , France

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Site 169

Nice, , France

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Site 114

Paris, , France

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Site 167

Paris, , France

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Site 136

Poitiers, , France

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Site 141

Rennes, , France

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Site 107

Rouen, , France

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Site 119

Toulouse, , France

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Site 142

Vandœuvre-lès-Nancy, , France

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Site 113

Villejuif, , France

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Site 101

Aachen, , Germany

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Site 121

Berlin, , Germany

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Site 165

Essen, , Germany

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Site 84

Giessen, , Germany

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Site 62

Greifswald, , Germany

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Site 79

Hamburg, , Germany

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Site 88

Hamburg, , Germany

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Site 112

Hanover, , Germany

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Site 116

Leipzig, , Germany

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Site 175

Mannheim, , Germany

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Site 168

München, , Germany

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Site 99

Würzburg, , Germany

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Site 91

Athens, , Greece

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Site 96

Athens, , Greece

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Site 120

Heraklion, , Greece

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Site 126

Rio, , Greece

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Site 83

Thessaloniki, , Greece

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Site 19

Haifa, , Israel

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Site 1

Jerusalem, , Israel

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Site 2

Tel Aviv, , Israel

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Site 14

Tel Litwinsky, , Israel

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Site 93

Brescia, , Italy

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Site 111

Cuneo, , Italy

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Site 128

Milan, , Italy

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Site 81

Milan, , Italy

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Site 89

Napoli, , Italy

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Site 85

Rozzano, , Italy

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Site 132

Chūōku, , Japan

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Site 192

Fukuoka, , Japan

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Site 131

Kashiwa, , Japan

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Site 135

Miki, , Japan

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Site 139

Nagoya, , Japan

Site Status RECRUITING

Site 186

Natori, , Japan

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Site 133

Ōsaka-sayama, , Japan

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Site 134

Sendai, , Japan

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Site 180

Kaunas, , Lithuania

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Site 181

Vilnius, , Lithuania

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Site 76

Amsterdam, , Netherlands

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Site 61

Nijmegen, , Netherlands

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Site 66

Utrecht, , Netherlands

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Site 190

Bydgoszcz, , Poland

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Site 143

Gdansk, , Poland

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Site 97

Gliwice, , Poland

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Site 177

Krakow, , Poland

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Site 117

Skorzewo, , Poland

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Site 179

Warsaw, , Poland

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Site 182

Coimbra, , Portugal

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Site 183

Lisbon, , Portugal

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Site 185

Porto, , Portugal

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Site 161

Busan, , South Korea

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Site 13

Goyang-si, , South Korea

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Site 29

Hwasun, , South Korea

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Site 137

Seoul, , South Korea

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Site 36

Seoul, , South Korea

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Site 47

Seoul, , South Korea

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Site 33

Soeul, , South Korea

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Site 164

Suwon, , South Korea

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Site 78

Barcelona, , Spain

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Site 109

Madrid, , Spain

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Site 75

Madrid, , Spain

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Site 71

Madrid, , Spain

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Site 166

Madrid, , Spain

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Site 63

Pamplona, , Spain

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Site 64

Pamplona, , Spain

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Site 74

Valencia, , Spain

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Site 184

Bellinzona, , Switzerland

Site Status RECRUITING

Site 189

Geneva, , Switzerland

Site Status RECRUITING

Site 178

Sankt Gallen, , Switzerland

Site Status RECRUITING

Site 41

Changhua, , Taiwan

Site Status WITHDRAWN

Site 17

Kaohsiung City, , Taiwan

Site Status RECRUITING

Site 95

Kaohsiung City, , Taiwan

Site Status RECRUITING

Site 53

Taichung, , Taiwan

Site Status RECRUITING

Site 176

Tainan, , Taiwan

Site Status RECRUITING

Site 39

Taipei, , Taiwan

Site Status RECRUITING

Site 35

Taipei, , Taiwan

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Site 52

Taoyuan, , Taiwan

Site Status RECRUITING

Site 65

Cambridge, , United Kingdom

Site Status RECRUITING

Site 174

Cardiff, , United Kingdom

Site Status RECRUITING

Site 171

Glasgow, , United Kingdom

Site Status RECRUITING

Site 44

Liverpool, , United Kingdom

Site Status RECRUITING

Site 157

London, , United Kingdom

Site Status RECRUITING

Site 140

London, , United Kingdom

Site Status RECRUITING

Site 90

London, , United Kingdom

Site Status RECRUITING

Site 42

London, , United Kingdom

Site Status RECRUITING

Site 48

Manchester, , United Kingdom

Site Status RECRUITING

Site 70

Middlesex, , United Kingdom

Site Status RECRUITING

Site 191

Newcastle upon Tyne, , United Kingdom

Site Status RECRUITING

Site 43

Sutton, , United Kingdom

Site Status RECRUITING

Countries

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United States Argentina Australia Belgium Brazil Canada Chile Czechia France Germany Greece Israel Italy Japan Lithuania Netherlands Poland Portugal South Korea Spain Switzerland Taiwan United Kingdom

Central Contacts

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David Yao, MD

Role: CONTACT

+1 617 401 4499

Eduardo Pennella, MD

Role: CONTACT

+1 617 401 4499

References

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Machiels JP, Fayette J, Haddad R, Adkins D, Gillison M, Harrington KJ, Kim SB, Le Tourneau C, Psyrri A, Rosenberg A, Siu LL, Tahara M, William WN Jr, Ford J, Jauhari S, Pyle R, Shen YM, Yao D, Zohren F, Vokes E. LiGeR-HN phase III trials of petosemtamab + pembrolizumab and petosemtamab monotherapy in recurrent or metastatic HNSCC. Future Oncol. 2025 Jul;21(16):2007-2016. doi: 10.1080/14796694.2025.2511470. Epub 2025 Jun 13.

Reference Type DERIVED
PMID: 40511820 (View on PubMed)

Other Identifiers

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2023-510322-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MCLA-158-CL02

Identifier Type: -

Identifier Source: org_study_id

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