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

NCT06525220 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: MCLA-158-CL032023-510323-30-00
• Study Type: interventional
• Target: 700
• Locations: 26 countries
• Sites: 197

Brief Summary

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.

Conditions

Head and Neck Squamous Cell Carcinoma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Overall Survival (OS)

  Up to approximately 3 years

• Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by blinded independent central review (BICR)

  Up to approximately 2 years

Secondary Outcomes (16)

• Progression Free Survival (PFS) per RECIST v1.1 as assessed by BICR

  Up to approximately 2 years

• Duration of Response (DOR) per RECIST v1.1 as assessed by BICR

  Up to approximately 2 years

• Clinical benefit rate per RECIST v1.1 as assessed by BICR

  Up to approximately 2 years

• Time to response (TTR) per RECIST v1.1 as assessed by BICR

  Time Frame: Up to approximately 2 years

• Objective response rate per RECIST v1.1 as assessed by investigator review

  Up to approximately 2 years

Study Arms (2)

Petosemtamab + Pembrolizumab

EXPERIMENTAL

Combination Therapy

Drug: Petosemtamab; Drug: Pembrolizumab

Pembrolizumab

ACTIVE COMPARATOR

Monotherapy

Drug: Pembrolizumab

Interventions

Petosemtamab DRUG

MCLA-158

Petosemtamab + Pembrolizumab

Pembrolizumab DRUG

Humanized Antibody

Pembrolizumab; Petosemtamab + Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Signed ICF before initiation of any study procedures
• Age ≥ 18 years at signing of ICF
• Histologically confirmed HNSCC with evidence of metastatic or locally recurrent disease not amenable to local therapy with curative intent.
• The eligible HNSCC primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.
• HNSCC patients eligible to receive pembrolizumab as 1L monotherapy with tumors expressing PD-L1, CPS ≥1.
• HNSCC patients should not have had previous systemic therapy administered in the incurable recurrent or metastatic setting
• A new tumor biopsy, unless the patient has an available archival tumor sample with sufficient material
• Measurable disease per Investigator assessment as defined by RECIST v1.1 by radiologic methods
• ECOG Performance Status (PS) of 0-1
• Life expectancy ≥ 12 weeks, as per investigator assessment.
• Left ventricular ejection fraction (LVEF) ≥50% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan
• Adequate organ function as defined per protocol.
• 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

You may not qualify if:

• 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
• Known leptomeningeal involvement
• Any systemic anticancer therapy or investigational drug within 4 weeks or 5 half-lives, whichever is shorter, before randomization
• Requirement for immunosuppressive medication
• Major surgery or radiotherapy within 3 weeks of randomization
• 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
• History of hypersensitivity reaction to any of the excipients of petosemtamab or pembrolizumab.
• 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
• History of prior malignancies within the last 5 years, with the exception of excised local cancer
• 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.
• 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
• 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

Sponsors & Collaborators

• Merus B.V.: lead

Study Sites (197)

Site 164

Mobile, Alabama, 36607, United States

RECRUITING

Site 36

La Jolla, California, 92037, United States

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Site 27

Los Angeles, California, 90033, United States

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Site 16

Palo Alto, California, 94304, United States

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Site 19

Newark, Delaware, 19713, United States

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Site 108

Washington D.C., District of Columbia, 20010, United States

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Site 14

Fort Myers, Florida, 33901, United States

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Site 48

Orlando, Florida, 32804, United States

WITHDRAWN

Site 8

Orlando, Florida, 32827, United States

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Site 21

St. Petersburg, Florida, 33705, United States

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Site 20

West Palm Beach, Florida, 33401, United States

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Site 171

Atlanta, Georgia, 30322, United States

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Site 197

Chicago, Illinois, 60611, United States

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Site 50

Chicago, Illinois, 60637, United States

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Site 2

Louisville, Kentucky, 40202, United States

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Site 162

Baton Rouge, Louisiana, 70809, United States

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Site 155

Minneapolis, Minnesota, 55417, United States

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Site 168

St Louis, Missouri, 63108, United States

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Site 94

Hackensack, New Jersey, 07601, United States

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Site 6

Albuquerque, New Mexico, 87131, United States

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Site 113

Durham, North Carolina, 27710, United States

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Site 118

Winston-Salem, North Carolina, 27157, United States

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Site 191

Cleveland, Ohio, 44195, United States

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Site 43

Philadelphia, Pennsylvania, 19104, United States

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Site 153

Philadelphia, Pennsylvania, 19107, United States

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Site 154

Philadelphia, Pennsylvania, 19114, United States

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Site 89

Chattanooga, Tennessee, 37404, United States

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Site 115

Memphis, Tennessee, 38103, United States

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Site 88

Nashville, Tennessee, 37203, United States

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Site 22

Austin, Texas, 78745, United States

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Site 1

Houston, Texas, 77030, United States

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Site 18

Plano, Texas, 75075, United States

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Site 17

Sugar Land, Texas, 77479, United States

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Site 15

Tyler, Texas, 75702, United States

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Site 10

Salt Lake City, Utah, 84112, United States

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Site 12

Blacksburg, Virginia, 24060, United States

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Site 23

Norfolk, Virginia, 23502, United States

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Site 170

CABA, C1113AAE, Argentina

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Site 96

CABA, C1118AAT, Argentina

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Site 37

CABA, C1125ABD, Argentina

WITHDRAWN

Site 31

Córdoba, X5008HHW, Argentina

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Site 30

La Rioja, 5300, Argentina

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Site 76

Rosario, S2000KZE, Argentina

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Site 46

Viedma, R8500ACE, Argentina

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Site 11

Blacktown, New South Wales, 2148, Australia

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Site 24

St Leonards, New South Wales, 2065, Australia

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Site 166

Greenslopes, Queensland, 4120, Australia

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Site 151

Melbourne, Victoria, 3004, Australia

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Site 53

Brussels, 1200, Belgium

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Site 98

Edegem, 2650, Belgium

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Site 99

Ghent, 9000, Belgium

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Site 71

Leuven, 3000, Belgium

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Site 109

Liège, 4000, Belgium

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Site 63

Namur, 5000, Belgium

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Site 141

Belo Horizonte, 30.360-680, Brazil

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Site 144

Natal, 59020-340, Brazil

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Site 140

Porto Alegre, 90610-000, Brazil

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Site 142

Porto Alegre, 91350-200, Brazil

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Site 137

Recife, 50040-000, Brazil

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Site 149

Rio de Janeiro, 22.250-905, Brazil

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Site 138

Rio de Janeiro, 22281-100, Brazil

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Site 134

São Paulo, 01509-900, Brazil

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Site 136

São Paulo, 04538-132, Brazil

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Site 165

St. John's, A1B3V6, Canada

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Site 44

Toronto, M5G 2M9, Canada

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Site 111

Winnipeg, R3E0V9, Canada

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Site 38

Antofagasta, 1263521, Chile

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Site 26

Providencia, 7500859, Chile

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Site 29

Recoleta, 8420000, Chile

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Site 40

Santiago, 7500921, Chile

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Site 32

Santiago, 7560908, Chile

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Site 34

Santiago, 8330336, Chile

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Site 25

Temuco, 76281055-7, Chile

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Site 195

Olomouc, 779 00, Czechia

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Site 192

Prague, 150 06, Czechia

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Site 56

Bordeaux, 33075, France

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Site 101

Le Mans, 72000, France

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Site 79

Lille, 59000, France

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Site 72

Lyon, 69378, France

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Site 57

Marseille, 13005, France

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Site 55

Montpellier, 34298, France

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Site 66

Nice, 06189, France

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Site 105

Paris, 75005, France

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Site 143

Paris, 75013, France

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Site 87

Poitiers, 86021, France

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Site 54

Rouen, 76038, France

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Site 59

Toulouse, 31100, France

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Site 64

Vandœuvre-lès-Nancy, 54519, France

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Site 112

Villejuif, 94800, France

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Site 133

Bonn, 53175, Germany

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Site 178

Dortmund, 44137, Germany

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Site 100

Dresden, 01307, Germany

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Site 60

Greifswald, 17475, Germany

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Site 82

Hamburg, 20251, Germany

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Site 91

Hamburg, 22763, Germany

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Site 104

Hanover, 30625, Germany

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Site 129

Mannheim, 68167, Germany

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Site 148

München, 81675, Germany

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Site 121

Münster, 48149, Germany

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Site 78

Tübingen, 72076, Germany

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Site 130

Ulm, 89075, Germany

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Site 110

Würzburg, 97080, Germany

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Site 119

Pátrai, Achaia, 265 04, Greece

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Site 156

Athens, Attica, 151 23, Greece

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Site 117

Heraklion, Crete, 715 00, Greece

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Site 95

Chaïdári, 12462, Greece

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Site 92

Panórama, 55236, Greece

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Site 194

Nyíregyháza, 4400, Hungary

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Site 189

Pécs, 7624, Hungary

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Site 187

Szeged, 6720, Hungary

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Site 9

Haifa, 3109601, Israel

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Site 5

Jerusalem, 9112001, Israel

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Site 3

Ramat Gan, 5266202, Israel

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Site 7

Tel Aviv, 6423906, Israel

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Site 86

Ancona, 60126, Italy

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Site 97

Brescia, 25123, Italy

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Site 180

Cagliari, 09121, Italy

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Site 139

Meldola, 47014, Italy

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Site 122

Milan, 20133, Italy

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Site 81

Milan, 20141, Italy

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Site 152

Naples, 80131, Italy

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Site 93

Naples, 80131, Italy

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Site 186

Rome, 00161, Italy

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Site 85

Rozzano, 20089, Italy

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Site 167

Nagoya, Aichi-ken, 464-8681, Japan

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Site 123

Kashiwa, Chiba, 277-8577, Japan

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Site 185

Fukuoka, Fukuoka, 810-8563, Japan

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Site 127

Hiragi, Kagawa-ken, 761-0793, Japan

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Site 174

Natori-shi, Miyagi, 981-1293, Japan

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Site 126

Sendai, Miyagi, 960-8574, Japan

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Site 125

Ōsaka-sayama, Osaka, 589-8511, Japan

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Site 124

Chuo Ku, Tokyo, 104-0045, Japan

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Site 188

Minato-Ku, Tokyo, 105-8471, Japan

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Site 183

Kaunas, 50161, Lithuania

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Site 179

Vilnius, 08406, Lithuania

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Site 163

Johor Bahru, 81100, Malaysia

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Site 159

Kuching, 93586, Malaysia

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Site 161

Putrajaya, 62250, Malaysia

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Site 84

Amsterdam, 1066 CX, Netherlands

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Site 58

Nijmegen, 6525 GA, Netherlands

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Site 68

Utrecht, 3584 CX, Netherlands

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Site 150

Bydgoszcz, 85-796, Poland

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Site 131

Gdansk, 80-214, Poland

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Site 106

Gliwice, 44-102, Poland

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Site 116

Krakow, 31-826, Poland

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Site 190

Lodz, 93-513, Poland

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Site 158

Warsaw, 02-781, Poland

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Site 172

Coimbra, 3004-561, Portugal

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Site 182

Lisbon, 1998-018, Portugal

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Site 181

Portimão, 8500-338, Portugal

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Site 175

Porto, 4200-072, Portugal

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Site 145

Busan, 48108, South Korea

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Site 13

Goyang-si, 10408, South Korea

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Site 47

Gyeonggi-do, 13496, South Korea

WITHDRAWN

Site 51

Hwasun, 58128, South Korea

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Site 28

Seoul, 03722, South Korea

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Site 35

Seoul, 03722, South Korea

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Site 45

Seoul, 05505, South Korea

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Site 42

Suwon, 16247, South Korea

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Site 157

Suwon, 16499, South Korea

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Site 120

Badalona, 08916, Spain

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Site 80

Barcelona, 08035, Spain

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Site 128

Madrid, 28040, Spain

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Site 75

Madrid, 28040, Spain

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Site 67

Madrid, 28041, Spain

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Site 160

Madrid, 28050, Spain

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Site 73

Marbella, 29660, Spain

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Site 61

Pamplona, 31008, Spain

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Site 62

Pamplona, 31008, Spain

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Site 74

Valencia, 46009, Spain

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Site 41

Changhua, 500, Taiwan

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Site 4

Kaohsiung City, 80756, Taiwan

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Site 103

Kaohsiung City, 833, Taiwan

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Site 52

Taichung, 40447, Taiwan

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Site 39

Taipei, 100, Taiwan

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Site 33

Taipei, 112, Taiwan

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Site 49

Taoyuan, 333, Taiwan

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Site 114

Bangkok Noi, Bangkok, 10700, Thailand

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Site 107

Pathum Wan, Bangkok, 10330, Thailand

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Site 65

Ratchathewi, Bangkok, 10400, Thailand

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Site 77

Hat Yai, Changwat Songkhla, 90110, Thailand

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Site 146

Chiang Rai, 57000, Thailand

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Site 196

Ankara, 06170, Turkey (Türkiye)

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Site 184

Ankara, 06230, Turkey (Türkiye)

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Site 176

Antalya, 07025, Turkey (Türkiye)

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Site 193

Istanbul, 34722, Turkey (Türkiye)

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Site 102

Cambridge, CB20QQ, United Kingdom

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Site 169

Cardiff, CF14 2TL, United Kingdom

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Site 132

London, EC1A 7BE, United Kingdom

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Site 90

London, SE19RT, United Kingdom

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Site 69

London, SW3 6JJ, United Kingdom

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Site 173

Manchester, M20 4BX, United Kingdom

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Site 177

Newcastle upon Tyne, NE7 7DN, United Kingdom

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Site 83

Northwood, HA62RN, United Kingdom

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Site 147

Southampton, SO16 6YD, United Kingdom

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Site 70

Sutton, SM2 5PT, United Kingdom

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Site 135

Taunton, TA1 5DA, United Kingdom

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Related Publications (1)

• 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.

  PMID: 40511820 DERIVED

MeSH Terms

Conditions

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

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Head of Clinical Operations

CONTACT

+1 617 401 4499; USenquiries@merus.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2024
• First Posted: July 29, 2024
• Study Start: September 25, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): July 1, 2030
• Last Updated: April 22, 2026

Record last verified: 2026-04

Locations

GR (5); US (37); TW (7); IL (4); MY (3); PL (6); KR (9); TU (4); GB (11); IT (10); JP (9); FR (14); AU (4); PT (4); ES (10); BE (6); DE (13); AR (7); TH (5); CA (3); CL (7); LI (2); NL (3); BR (9); HU (3); CZ (2)