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

NCT06496178 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: MCLA-158-CL022023-510322-32-00
• Study Type: interventional
• Target: 500
• Locations: 24 countries
• Sites: 208

Brief Summary

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.

Conditions

Head and Neck Squamous Cell Carcinoma

Keywords

HNSCC

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review

  ORR was defined as the proportion of participants in the analysis population who had a Complete Response or Partial Response based per RECIST v1.1 with confirmation.

  Up to approximately 2 years

• Overall Survival (OS)

  OS was defined as the time from randomization to death due to any cause.

  Up to approximately 3 years

Secondary Outcomes (18)

• Progression Free Survival (PFS) as Assessed by Blinded Independent Central Review

  Up to approximately 2 years

• Duration of Response (DOR) as Assessed by Blinded Independent Central Review

  Up to approximately 2 years

• Objective Response Rate (ORR) as Assessed by Investigator Review

  Up to approximately 2 years

• Progression Free Survival (PFS) as Assessed by Investigator Review

  Up to approximately 2 years

• Duration of Response (DOR) as Assessed by Investigator Review

  Up to approximately 2 years

Study Arms (2)

MCLA-158

EXPERIMENTAL

Drug: Petosemtamab

Investigator's Choice

ACTIVE COMPARATOR

Drug: Investigator's Choice

Interventions

Petosemtamab DRUG

MCLA-158

MCLA-158

Investigator's Choice DRUG

Cetuximab

Investigator's Choice

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 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)

You may not qualify if:

• 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).

Sponsors & Collaborators

• Merus B.V.: lead

Study Sites (208)

Site 160

Mobile, Alabama, 36608, United States

RECRUITING

Site 102

Prescott, Arizona, 86301, United States

COMPLETED

Site 125

Scottsdale, Arizona, 85054, United States

RECRUITING

Site 82

Duarte, California, 91010, United States

RECRUITING

Site 25

La Jolla, California, 92037, United States

RECRUITING

Site 173

Orange, California, 92868, United States

RECRUITING

Site 28

Palo Alto, California, 94304, United States

RECRUITING

Site 127

Sacramento, California, 95817, United States

RECRUITING

Site 46

San Francisco, California, 94158, United States

RECRUITING

Site 130

Lone Tree, Colorado, 80124, United States

RECRUITING

Site 104

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

RECRUITING

Site 12

Fort Myers, Florida, 33901, United States

RECRUITING

Site 123

Jacksonville, Florida, 32224, United States

RECRUITING

Site 9

Orlando, Florida, 32827, United States

RECRUITING

Site 138

Tampa, Florida, 33612, United States

RECRUITING

Site 187

Atlanta, Georgia, 30322, United States

RECRUITING

Site 207

Atlanta, Georgia, 30341, United States

RECRUITING

Site 152

Chicago, Illinois, 60607, United States

RECRUITING

Site 68

Chicago, Illinois, 60637, United States

RECRUITING

Site 31

Indianapolis, Indiana, 46202, United States

RECRUITING

Site 8

Louisville, Kentucky, 40202, United States

RECRUITING

Site 40

Baton Rouge, Louisiana, 70809, United States

RECRUITING

Site 100

New Orleans, Louisiana, 70121, United States

RECRUITING

Site 153

Columbia, Maryland, 21044, United States

RECRUITING

Site 77

Boston, Massachusetts, 02215, United States

RECRUITING

Site 103

Ann Arbor, Michigan, 48109, United States

RECRUITING

Site 5

Detroit, Michigan, 48201, United States

RECRUITING

Site 49

Maple Grove, Minnesota, 55369, United States

RECRUITING

Site 124

Rochester, Minnesota, 55905, United States

RECRUITING

Site 18

St Louis, Missouri, 63110, United States

RECRUITING

Site 86

Hackensack, New Jersey, 07601, United States

RECRUITING

Site 15

Albuquerque, New Mexico, 87131, United States

RECRUITING

Site 24

New York, New York, 10029, United States

RECRUITING

Site 98

Chapel Hill, North Carolina, 27514, United States

RECRUITING

Site 122

Durham, North Carolina, 27710, United States

RECRUITING

Site 23

Cincinnati, Ohio, 45219, United States

RECRUITING

Site 87

Cleveland, Ohio, 44195, United States

RECRUITING

Site 32

Columbus, Ohio, 43210, United States

RECRUITING

Site 26

Portland, Oregon, 97213, United States

RECRUITING

Site 151

Bensalem, Pennsylvania, 19020, United States

RECRUITING

Site 158

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Site 159

Philadelphia, Pennsylvania, 19114, United States

RECRUITING

Site 50

Charleston, South Carolina, 29425, United States

RECRUITING

Site 60

Chattanooga, Tennessee, 37404, United States

RECRUITING

Site 54

Memphis, Tennessee, 38103, United States

RECRUITING

Site 59

Nashville, Tennessee, 37203, United States

RECRUITING

Site 67

Nashville, Tennessee, 37232, United States

RECRUITING

Site 55

Denison, Texas, 75020, United States

RECRUITING

Site 34

El Paso, Texas, 79915, United States

RECRUITING

Site 51

Houston, Texas, 77030, United States

RECRUITING

Site 7

Houston, Texas, 77030, United States

RECRUITING

Site 94

Pearland, Texas, 77584, United States

RECRUITING

Site 4

Salt Lake City, Utah, 84112, United States

RECRUITING

Site 10

Blacksburg, Virginia, 24060, United States

RECRUITING

Site 22

Charlottesville, Virginia, 22908, United States

RECRUITING

Site 156

Winchester, Virginia, 22601, United States

RECRUITING

Site 163

Seattle, Washington, 98109, United States

RECRUITING

Site 6

Spokane, Washington, 99202, United States

RECRUITING

Site 37

Buenos Aires, C1125ABD, Argentina

WITHDRAWN

Site 80

Buenos Aires, C1426ANZ, Argentina

WITHDRAWN

Site 58

Caba, C1280AEB, Argentina

RECRUITING

Site 193

CABA, Clll3AAE, Argentina

RECRUITING

Site 45

Córdoba, X5008HHW, Argentina

RECRUITING

Site 110

Rosario, S2000KZE, Argentina

RECRUITING

Site 57

Viedma, 8500, Argentina

RECRUITING

Site 3

Darlinghurst, 2010, Australia

RECRUITING

Site 170

Herston, 4060, Australia

RECRUITING

Site 38

Melbourne, 3000, Australia

RECRUITING

Site 30

Nedlands, 6009, Australia

RECRUITING

Site 11

Saint Leonards, 2065, Australia

RECRUITING

Site 73

Sydney, 2050, Australia

RECRUITING

Site 129

Brussels, 1070, Belgium

WITHDRAWN

Site 56

Brussels, 1200, Belgium

RECRUITING

Site 92

Ghent, 9000, Belgium

RECRUITING

Site 72

Leuven, 3000, Belgium

RECRUITING

Site 108

Liège, 4000, Belgium

RECRUITING

Site 69

Namur, 5000, Belgium

RECRUITING

Site 154

Brasília, 70390-140, Brazil

RECRUITING

Site 145

Porto Alegre, 90110-270, Brazil

RECRUITING

Site 150

Porto Alegre, 90610-000, Brazil

RECRUITING

Site 146

Recife, 50040-000, Brazil

RECRUITING

Site 155

Rio de Janeiro, 22.250-905, Brazil

RECRUITING

Site 148

Rio de Janeiro, 22281-100, Brazil

RECRUITING

Site 147

São Paulo, 01509-900, Brazil

RECRUITING

Site 144

São Paulo, 04538-132, Brazil

RECRUITING

Site 172

Montreal, H2X 0A9, Canada

RECRUITING

Site 196

Toronto, M4N 3M5, Canada

RECRUITING

Site 16

Providencia, 7500859, Chile

RECRUITING

Site 20

Recoleta, 8420000, Chile

RECRUITING

Site 27

Santiago, 7500921, Chile

RECRUITING

Site 21

Santiago, 7560908, Chile

RECRUITING

Site 188

Nový Jičín, 74101, Czechia

RECRUITING

Site 201

Olomouc, 779 00, Czechia

RECRUITING

Site 202

Prague, 150 06, Czechia

RECRUITING

Site 105

Bordeaux, 33075, France

RECRUITING

Site 162

Le Mans, 72000, France

RECRUITING

Site 149

Lille, 59000, France

RECRUITING

Site 118

Lyon, 69373, France

RECRUITING

Site 115

Marseille, 13005, France

RECRUITING

Site 106

Montpellier, 34298, France

RECRUITING

Site 169

Nice, 06189, France

RECRUITING

Site 114

Paris, 75005, France

RECRUITING

Site 167

Paris, 75013, France

RECRUITING

Site 136

Poitiers, 86000, France

RECRUITING

Site 141

Rennes, 35042, France

RECRUITING

Site 107

Rouen, 76038, France

RECRUITING

Site 119

Toulouse, 31059, France

RECRUITING

Site 142

Vandœuvre-lès-Nancy, 54519, France

RECRUITING

Site 113

Villejuif, 94800, France

RECRUITING

Site 101

Aachen, 52074, Germany

RECRUITING

Site 121

Berlin, 12203, Germany

RECRUITING

Site 165

Essen, 45147, Germany

RECRUITING

Site 84

Giessen, 35390, Germany

RECRUITING

Site 62

Greifswald, 17475, Germany

RECRUITING

Site 79

Hamburg, 20246, Germany

RECRUITING

Site 88

Hamburg, 22763, Germany

RECRUITING

Site 112

Hanover, 30625, Germany

RECRUITING

Site 116

Leipzig, 04103, Germany

RECRUITING

Site 175

Mannheim, 68167, Germany

RECRUITING

Site 168

München, 81675, Germany

RECRUITING

Site 99

Würzburg, 97080, Germany

RECRUITING

Site 91

Athens, 124 62, Greece

RECRUITING

Site 96

Athens, 15123, Greece

RECRUITING

Site 120

Heraklion, 71500, Greece

RECRUITING

Site 126

Rio, 26504, Greece

RECRUITING

Site 83

Thessaloniki, 55236, Greece

RECRUITING

Site 204

Nyíregyháza, 4400, Hungary

RECRUITING

Site 195

Pécs, 7624, Hungary

RECRUITING

Site 198

Szeged, 6725, Hungary

RECRUITING

Site 19

Haifa, 3109601, Israel

RECRUITING

Site 1

Jerusalem, 9112001, Israel

RECRUITING

Site 14

Ramat Gan, 5265601, Israel

RECRUITING

Site 2

Tel Aviv, 6423906, Israel

RECRUITING

Site 93

Brescia, 25123, Italy

RECRUITING

Site 111

Cuneo, 12100, Italy

RECRUITING

Site 128

Milan, 20133, Italy

RECRUITING

Site 81

Milan, 20141, Italy

RECRUITING

Site 89

Naples, 80131, Italy

RECRUITING

Site 203

Roma, 00161, Italy

RECRUITING

Site 85

Rozzano, 20089, Italy

RECRUITING

Site 132

Chūōku, 104-0045, Japan

RECRUITING

Site 199

Fukuoka, 810-8563, Japan

RECRUITING

Site 192

Fukuoka, 812-8582, Japan

RECRUITING

Site 131

Kashiwa, 277-8577, Japan

RECRUITING

Site 135

Miki, 761-0793, Japan

RECRUITING

Site 205

Minatoku, 105-8471, Japan

RECRUITING

Site 139

Nagoya, 464-8681, Japan

RECRUITING

Site 186

Natori, 981-1293, Japan

RECRUITING

Site 133

Ōsaka-sayama, 589-8511, Japan

RECRUITING

Site 134

Sendai, 980-8574, Japan

RECRUITING

Site 180

Kaunas, 50161, Lithuania

RECRUITING

Site 181

Vilnius, 08406, Lithuania

RECRUITING

Site 76

Amsterdam, 1066 CX, Netherlands

RECRUITING

Site 61

Nijmegen, 6525 GA, Netherlands

RECRUITING

Site 66

Utrecht, 3584 CX, Netherlands

RECRUITING

Site 190

Bydgoszcz, 85-796, Poland

RECRUITING

Site 143

Gdansk, 80-214, Poland

RECRUITING

Site 97

Gliwice, 44-102, Poland

RECRUITING

Site 177

Krakow, 31-826, Poland

RECRUITING

Site 200

Lodz, 93-513, Poland

RECRUITING

Site 117

Poznan, 60-185, Poland

RECRUITING

Site 179

Warsaw, 02-781, Poland

RECRUITING

Site 182

Coimbra, 3004-561, Portugal

RECRUITING

Site 183

Lisbon, 1998-018, Portugal

RECRUITING

Site 197

Portimão, 8500-338, Portugal

RECRUITING

Site 185

Porto, 4200-072, Portugal

RECRUITING

Site 161

Busan, 48108, South Korea

RECRUITING

Site 13

Goyang-si, 10408, South Korea

RECRUITING

Site 29

Hwasun, 58128, South Korea

RECRUITING

Site 206

Seongnam-si, 13620, South Korea

RECRUITING

Site 137

Seoul, 03080, South Korea

RECRUITING

Site 36

Seoul, 05505, South Korea

RECRUITING

Site 47

Seoul, 06351, South Korea

RECRUITING

Site 208

Seoul, 07061, South Korea

RECRUITING

Site 33

Soeul, 03722, South Korea

RECRUITING

Site 164

Suwon, 16499, South Korea

RECRUITING

Site 78

Barcelona, 08035, Spain

RECRUITING

Site 109

Madrid, 28040, Spain

RECRUITING

Site 75

Madrid, 28040, Spain

RECRUITING

Site 71

Madrid, 28041, Spain

RECRUITING

Site 166

Madrid, 28050, Spain

RECRUITING

Site 63

Pamplona, 31008, Spain

RECRUITING

Site 64

Pamplona, 31008, Spain

RECRUITING

Site 74

Valencia, 46009, Spain

RECRUITING

Site 184

Bellinzona, CH-6500, Switzerland

RECRUITING

Site 189

Geneva, 1211, Switzerland

RECRUITING

Site 194

Lausanne, 1011, Switzerland

RECRUITING

Site 178

Sankt Gallen, 9007, Switzerland

RECRUITING

Site 41

Changhua, 500, Taiwan

WITHDRAWN

Site 17

Kaohsiung City, 807, Taiwan

RECRUITING

Site 95

Kaohsiung City, 833, Taiwan

RECRUITING

Site 53

Taichung, 40447, Taiwan

RECRUITING

Site 176

Tainan, 70428, Taiwan

RECRUITING

Site 39

Taipei, 100, Taiwan

RECRUITING

Site 35

Taipei, 112, Taiwan

RECRUITING

Site 52

Taoyuan, 333, Taiwan

RECRUITING

Site 65

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

Site 174

Cardiff, CF14 2TL, United Kingdom

RECRUITING

Site 171

Glasgow, G12 0YN, United Kingdom

RECRUITING

Site 44

Liverpool, L7 8YA, United Kingdom

RECRUITING

Site 157

London, E20 1JQ, United Kingdom

RECRUITING

Site 140

London, EC1A 7BE, United Kingdom

RECRUITING

Site 90

London, SE1 9RT, United Kingdom

RECRUITING

Site 42

London, SW3 6JJ, United Kingdom

RECRUITING

Site 48

Manchester, M20 4BX, United Kingdom

RECRUITING

Site 70

Middlesex, HA6 2RN, United Kingdom

RECRUITING

Site 191

Newcastle upon Tyne, NE7 7DN, United Kingdom

RECRUITING

Site 43

Sutton, SM2 5PT, United Kingdom

RECRUITING

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

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Central Study Contacts

David Yao, MD

CONTACT

+1 617 401 4499; USenquiries@merus.nl

Eduardo Pennella, MD

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 3, 2024
• First Posted: July 11, 2024
• Study Start: June 25, 2024
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: March 31, 2026

Record last verified: 2026-03

Locations

GB (12); PT (4); AR (7); CA (2); TW (8); NL (3); KR (10); PL (7); HU (3); BR (8); CL (4); CZ (3); CH (4); FR (15); GR (5); JP (10); LI (2); ES (8); DE (12); AU (6); US (58); BE (6); IL (4); IT (7)