A Phase 3 Study to Evaluate Petosemtamab Plus Pembrolizumab vs Pembrolizumab in First-line Treatment of Head and Neck Cancer (LiGeR - HN1)

NCT ID: NCT06525220

Last Updated: 2025-12-19

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

2024-09-25

Study Completion Date

2030-07-31

Brief Summary

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This is a Phase 3 randomized, open-label study to evaluate the efficacy and safety of petosemtamab plus pembrolizumab vs pembrolizumab in first-line treatment of recurrent or metastatic PD-L1+ head and neck squamous cell carcinoma.

Detailed Description

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This is a Phase 3 randomized, open-label study to evaluate the efficacy and safety of petosemtamab plus pembrolizumab vs pembrolizumab in first-line treatment of recurrent or metastatic PD-L1+ HNSCC. HNSCC patients should not have had previous systemic therapy administered in the incurable recurrent or metastatic setting, although previous systemic therapy as part of multimodal treatment for locally advanced disease is allowed if PD was ≥6 months after the last platinum-containing therapy dose. Previous treatments with anti PD-(L)1 or anti-EGFR therapies are not allowed. In the case of cetuximab, patients who have received cetuximab with radiotherapy as a local treatment and PD was \>1 year after the last dose of cetuximab are eligible.

Conditions

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Head and Neck Squamous Cell Carcinoma

Keywords

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HNSCC PD-L1+ Head and Neck cancer Petosemtamab Pembrolizumab Liger Oral Cavity Oropharynx Larynx Hypopharynx

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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Petosemtamab + Pembrolizumab

Combination Therapy

Group Type EXPERIMENTAL

Petosemtamab

Intervention Type DRUG

MCLA-158

Pembrolizumab

Intervention Type DRUG

Humanized Antibody

Pembrolizumab

Monotherapy

Group Type ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type DRUG

Humanized Antibody

Interventions

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Petosemtamab

MCLA-158

Intervention Type DRUG

Pembrolizumab

Humanized Antibody

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Signed ICF before initiation of any study procedures
2. Age ≥ 18 years at signing of ICF
3. Histologically confirmed HNSCC with evidence of metastatic or locally recurrent disease not amenable to local therapy with curative intent.
4. The eligible HNSCC primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.
5. HNSCC patients eligible to receive pembrolizumab as 1L monotherapy with tumors expressing PD-L1, CPS ≥1.
6. HNSCC patients should not have had previous systemic therapy administered in the incurable recurrent or metastatic setting
7. A new tumor biopsy, unless the patient has an available archival tumor sample with sufficient material
8. Measurable disease per Investigator assessment as defined by RECIST v1.1 by radiologic methods
9. ECOG Performance Status (PS) of 0-1
10. Life expectancy ≥ 12 weeks, as per investigator assessment.
11. Left ventricular ejection fraction (LVEF) ≥50% or ≥ institutional normal limit, whichever is higher, by echocardiogram (ECHO) or multigated acquisition (MUGA) scan
12. Adequate organ function as defined per protocol.
13. HIV-positive patients are eligible only if the cluster of differentiation 4 (CD4+) count is ≥ 300/µl, viral load is undetectable, and the patient is currently receiving highly active antiretroviral therapy

Exclusion Criteria

1. Central nervous system metastases that are untreated or already treated but symptomatic, or require radiation, surgery, or continued steroid therapy to control symptoms within 21 days prior to randomization
2. Known leptomeningeal involvement
3. Any systemic anticancer therapy or investigational drug within 4 weeks or 5 half-lives, whichever is shorter, before randomization
4. Requirement for immunosuppressive medication
5. Major surgery or radiotherapy within 3 weeks of randomization
6. Clinically significant toxicities related to prior anticancer therapies that have not returned to ≤ Grade 1 or baseline except for Grade ≤2- myalgia, neuropathy, alopecia, and any prior therapy related endocrinopathies
7. History of hypersensitivity reaction to any of the excipients of petosemtomab or pembrolizumab.
8. 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 prior to randomization
9. History of prior malignancies within the last 5 years, with the exception of excised local cancer
10. Current dyspnea at rest of any origin, or other diseases requiring continuous oxygen therapy
11. Current serious illness or medical conditions including, but not limited to, uncontrolled active infection, clinically significant pulmonary, metabolic or psychiatric disorders
12. Patients with known infectious diseases as per protocol.
13. Pregnant or breastfeeding patients.
14. The patient has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy of prednisone \>10 mg/day or equivalent, or any other form of immunosuppressive therapy
15. The patient has an active autoimmune disease that has required systemic immune suppressive treatment in the past 2 years; replacement therapy is not considered immune suppressive treatment
16. The patient has had an allogeneic tissue/solid organ transplant.
17. Patient has a primary tumor site of nasopharynx, or sinonasal carcinoma (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 164

Mobile, Alabama, United States

Site Status RECRUITING

Site 36

La Jolla, California, United States

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Site 27

Los Angeles, California, United States

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Site 16

Palo Alto, California, United States

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Site 19

Newark, Delaware, United States

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Site 108

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

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Site 14

Fort Myers, Florida, United States

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Site 48

Orlando, Florida, United States

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Site 8

Orlando, Florida, United States

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Site 21

St. Petersburg, Florida, United States

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Site 20

West Palm Beach, Florida, United States

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Site 171

Atlanta, Georgia, United States

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Site 50

Chicago, Illinois, United States

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Site 2

Louisville, Kentucky, United States

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Site 162

Baton Rouge, Louisiana, United States

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Site 155

Minneapolis, Minnesota, United States

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Site 168

St Louis, Missouri, United States

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Site 94

Hackensack, New Jersey, United States

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Site 6

Albuquerque, New Mexico, United States

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Site 113

Durham, North Carolina, United States

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Site 118

Winston-Salem, North Carolina, United States

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Site 43

Philadelphia, Pennsylvania, United States

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Site 153

Philadelphia, Pennsylvania, United States

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Site 154

Philadelphia, Pennsylvania, United States

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Site 89

Chattanooga, Tennessee, United States

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Site 115

Memphis, Tennessee, United States

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Site 88

Nashville, Tennessee, United States

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Site 22

Austin, Texas, United States

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Site 1

Houston, Texas, United States

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Site 18

Plano, Texas, United States

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Site 17

Sugarland, Texas, United States

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Site 15

Tyler, Texas, United States

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Site 10

Salt Lake City, Utah, United States

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Site 12

Blacksburg, Virginia, United States

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Site 23

Norfolk, Virginia, United States

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Site 170

CABA, , Argentina

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Site 96

CABA, , Argentina

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Site 37

CABA, , Argentina

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Site 31

Córdoba, , Argentina

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Site 30

La Rioja, , Argentina

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Site 76

Rosario, , Argentina

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Site 46

Viedma, , Argentina

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Site 11

Blacktown, New South Wales, Australia

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Site 24

St Leonards, New South Wales, Australia

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Site 166

Greenslopes, Queensland, Australia

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Site 151

Melbourne, Victoria, Australia

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Site 53

Brussels, , Belgium

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Site 98

Edegem, , Belgium

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Site 99

Ghent, , Belgium

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Site 71

Leuven, , Belgium

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Site 109

Liège, , Belgium

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Site 63

Namur, , Belgium

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Site 149

Rio de Janeiro, Rio de Janeiro, Brazil

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Site 141

Belo Horizonte, , Brazil

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Site 144

Natal, , Brazil

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Site 140

Porto Alegre, , Brazil

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Site 142

Porto Alegre, , Brazil

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Site 137

Recife, , Brazil

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Site 138

Rio de Janeiro, , Brazil

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Site 134

São Paulo, , Brazil

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Site 136

São Paulo, , Brazil

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Site 165

St. John's, , Canada

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Site 44

Toronto, , Canada

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Site 111

Winnipeg, , Canada

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Site 38

Antofagasta, , Chile

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Site 26

Providencia, , Chile

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Site 29

Recoleta, , Chile

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Site 40

Santiago, , Chile

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Site 32

Santiago, , Chile

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Site 34

Santiago, , Chile

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Site 25

Temuco, , Chile

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Site 56

Bordeaux, , France

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Site 101

Le Mans, , France

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Site 79

Lille, , France

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Site 72

Lyon, , France

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Site 57

Marseille, , France

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Site 55

Montpellier, , France

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Site 66

Nice, , France

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Site 105

Paris, , France

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Site 143

Paris, , France

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Site 87

Poitiers, , France

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Site 54

Rouen, , France

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Site 59

Toulouse, , France

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Site 64

Vandœuvre-lès-Nancy, , France

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Site 112

Villejuif, , France

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Site 133

Bonn, , Germany

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Site 100

Dresden, , Germany

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Site 60

Greifswald, , Germany

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Site 82

Hamburg, , Germany

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Site 91

Hamburg, , Germany

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Site 104

Hanover, , Germany

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Site 129

Mannheim, , Germany

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Site 148

München, , Germany

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Site 121

Münster, , Germany

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Site 78

Tübingen, , Germany

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Site 130

Ulm, , Germany

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Site 110

Würzburg, , Germany

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Site 119

Pátrai, Achaia, Greece

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Site 156

Athens, Attica, Greece

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Site 117

Heraklion, Crete, Greece

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Site 95

Chaïdári, , Greece

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Site 92

Panórama, , Greece

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Site 9

Haifa, , Israel

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Site 5

Jerusalem, , Israel

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Site 3

Ramat Gan, , Israel

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Site 7

Tel Aviv, , Israel

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Site 86

Ancona, , Italy

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Site 97

Brescia, , Italy

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Site 139

Meldola, , Italy

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Site 122

Milan, , Italy

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Site 81

Milan, , Italy

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Site 152

Naples, , Italy

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Site 93

Naples, , Italy

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Site 85

Rozzano, , Italy

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Site 167

Nagoya, Aichi-ken, Japan

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Site 123

Kashiwa, Chiba, Japan

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Site 127

Hiragi, Kagawa-ken, Japan

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Site 174

Natori-shi, Miyagi, Japan

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Site 126

Sendai, Miyagi, Japan

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Site 125

Ōsaka-sayama, Osaka, Japan

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Site 124

Chuo Ku, Tokyo, Japan

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Site 163

Johor Bahru, , Malaysia

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Site 159

Kuching, , Malaysia

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Site 161

Putrajaya, , Malaysia

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Site 84

Amsterdam, , Netherlands

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Site 58

Nijmegen, , Netherlands

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Site 68

Utrecht, , Netherlands

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Site 150

Bydgoszcz, , Poland

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Site 131

Gdansk, , Poland

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Site 106

Gliwice, , Poland

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Site 116

Krakow, , Poland

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Site 158

Warsaw, , Poland

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Site 172

Coimbra, , Portugal

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Site 175

Porto, , Portugal

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Site 145

Busan, , South Korea

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Site 13

Goyang-si, , South Korea

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Site 47

Gyeonggi-do, , South Korea

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Site 51

Hwasun, , South Korea

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Site 28

Seoul, , South Korea

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Site 35

Seoul, , South Korea

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Site 45

Seoul, , South Korea

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Site 42

Suwon, , South Korea

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Site 157

Suwon, , South Korea

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Site 120

Badalona, , Spain

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Site 80

Barcelona, , Spain

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Site 128

Madrid, , Spain

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Site 75

Madrid, , Spain

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Site 67

Madrid, , Spain

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Site 160

Madrid, , Spain

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Site 73

Marbella, , Spain

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Site 61

Pamplona, , Spain

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Site 62

Pamplona, , Spain

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Site 74

Valencia, , Spain

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Site 41

Changhua, , Taiwan

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Site 4

Kaohsiung City, , Taiwan

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Site 103

Kaohsiung City, , Taiwan

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Site 52

Taichung, , Taiwan

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Site 39

Taipei, , Taiwan

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Site 33

Taipei, , Taiwan

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Site 49

Taoyuan, , Taiwan

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Site 114

Bangkok Noi, Bangkok, Thailand

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Site 107

Pathum Wan, Bangkok, Thailand

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Site 65

Ratchathewi, Bangkok, Thailand

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Site 146

Chiang Rai, Changwat Chiang Rai, Thailand

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Site 77

Hat Yai, Changwat Songkhla, Thailand

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Site 102

Cambridge, , United Kingdom

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Site 169

Cardiff, , United Kingdom

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Site 132

London, , United Kingdom

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Site 90

London, , United Kingdom

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Site 69

London, , United Kingdom

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Site 173

Manchester, , United Kingdom

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Site 83

Northwood, , United Kingdom

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Site 147

Southampton, , United Kingdom

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Site 70

Sutton, , United Kingdom

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Site 135

Taunton, , United Kingdom

Site Status RECRUITING

Countries

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

Central Contacts

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Head of Clinical Operations

Role: CONTACT

Phone: +1 617 401 4499

Email: [email protected]

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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MCLA-158-CL03

Identifier Type: -

Identifier Source: org_study_id

2023-510323-30-00

Identifier Type: CTIS

Identifier Source: secondary_id