A Phase 3 Study to Evaluate Petosemtamab Compared With Investigator's Choice Monotherapy in Previously Treated Head and Neck Squamous Cell Carcinoma Patients (LiGeR-HN2)
August 27, 2026 updated by: Merus B.V.
A Phase 3 Open-label, Randomized Controlled Study to Evaluate the Efficacy and Safety of Petosemtamab Compared With Investigator's Choice Monotherapy Treatment in Previously Treated Patients With Incurable, Metastatic/Recurrent Head and Neck Squamous Cell Carcinoma
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.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Interventional
Enrollment (Actual)
621
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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CABA, Argentina, Clll3AAE
- Site 193
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Caba, Argentina, C1280AEB
- Site 58
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Córdoba, Argentina, X5008HHW
- Site 45
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Rosario, Argentina, S2000KZE
- Site 110
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Viedma, Argentina, 8500
- Site 57
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Darlinghurst, Australia, 2010
- Site 3
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Herston, Australia, 4060
- Site 170
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Melbourne, Australia, 3000
- Site 38
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Nedlands, Australia, 6009
- Site 30
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Saint Leonards, Australia, 2065
- Site 11
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Sydney, Australia, 2050
- Site 73
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Brussels, Belgium, 1200
- Site 56
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Ghent, Belgium, 9000
- Site 92
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Leuven, Belgium, 3000
- Site 72
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Liège, Belgium, 4000
- Site 108
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Namur, Belgium, 5000
- Site 69
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Brasília, Brazil, 70390-140
- Site 154
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Porto Alegre, Brazil, 90110-270
- Site 145
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Porto Alegre, Brazil, 90610-000
- Site 150
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Recife, Brazil, 50040-000
- Site 146
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Rio de Janeiro, Brazil, 22281-100
- Site 148
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São Paulo, Brazil, 01509-900
- Site 147
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São Paulo, Brazil, 04538-132
- Site 144
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Montreal, Canada, H2X 0A9
- Site 172
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Toronto, Canada, M4N 3M5
- Site 196
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Providencia, Chile, 7500859
- Site 16
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Recoleta, Chile, 8420000
- Site 20
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Santiago, Chile, 7500921
- Site 27
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Santiago, Chile, 7560908
- Site 21
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Nový Jičín, Czechia, 74101
- Site 188
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Olomouc, Czechia, 779 00
- Site 201
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Bordeaux, France, 33075
- Site 105
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Brest, France, 29200
- Site 211
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Le Mans, France, 72000
- Site 162
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Lille, France, 59000
- Site 149
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Lyon, France, 69373
- Site 118
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Marseille, France, 13005
- Site 115
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Montpellier, France, 34298
- Site 106
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Nice, France, 06189
- Site 169
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Paris, France, 75005
- Site 114
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Paris, France, 75013
- Site 167
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Poitiers, France, 86000
- Site 136
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Rennes, France, 35042
- Site 141
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Rouen, France, 76038
- Site 107
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Toulouse, France, 31059
- Site 119
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Vandœuvre-lès-Nancy, France, 54519
- Site 142
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Villejuif, France, 94800
- Site 113
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Berlin, Germany, 12203
- Site 121
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Dresden, Germany, 01307
- Site 210
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Essen, Germany, 45147
- Site 165
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Giessen, Germany, 35390
- Site 84
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Greifswald, Germany, 17475
- Site 62
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Hamburg, Germany, 20246
- Site 79
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Hanover, Germany, 30625
- Site 112
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Leipzig, Germany, 04103
- Site 116
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München, Germany, 81675
- Site 168
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Würzburg, Germany, 97080
- Site 99
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Athens, Greece, 124 62
- Site 91
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Athens, Greece, 15123
- Site 96
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Heraklion, Greece, 71500
- Site 120
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Rio, Greece, 26504
- Site 126
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Thessaloniki, Greece, 55236
- Site 83
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Nyíregyháza, Hungary, 4400
- Site 204
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Pécs, Hungary, 7624
- Site 195
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Szeged, Hungary, 6725
- Site 198
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Haifa, Israel, 3109601
- Site 19
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Jerusalem, Israel, 9112001
- Site 1
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Ramat Gan, Israel, 5265601
- Site 14
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Tel Aviv, Israel, 6423906
- Site 2
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Brescia, Italy, 25123
- Site 93
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Cuneo, Italy, 12100
- Site 111
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Milan, Italy, 20133
- Site 128
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Milan, Italy, 20141
- Site 81
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Naples, Italy, 80131
- Site 209
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Naples, Italy, 80131
- Site 89
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Roma, Italy, 00161
- Site 203
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Rozzano, Italy, 20089
- Site 85
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Chūōku, Japan, 104-0045
- Site 132
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Fukuoka, Japan, 810-8563
- Site 199
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Fukuoka, Japan, 812-8582
- Site 192
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Kashiwa, Japan, 277-8577
- Site 131
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Miki, Japan, 761-0793
- Site 135
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Minatoku, Japan, 105-8471
- Site 205
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Nagoya, Japan, 464-8681
- Site 139
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Natori, Japan, 981-1293
- Site 186
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Sendai, Japan, 980-8574
- Site 134
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Ōsaka-sayama, Japan, 589-8511
- Site 133
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Aichi-ken
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Nagoya, Aichi-ken, Japan, 466-8560
- Site 217
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Kaunas, Lithuania, 50161
- Site 180
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Vilnius, Lithuania, 08406
- Site 181
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Amsterdam, Netherlands, 1066 CX
- Site 76
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Nijmegen, Netherlands, 6525 GA
- Site 61
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Utrecht, Netherlands, 3584 CX
- Site 66
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Bydgoszcz, Poland, 85-796
- Site 190
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Gdansk, Poland, 80-214
- Site 143
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Gliwice, Poland, 44-102
- Site 97
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Krakow, Poland, 31-826
- Site 177
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Lodz, Poland, 93-513
- Site 200
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Poznan, Poland, 60-185
- Site 117
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Warsaw, Poland, 02-781
- Site 179
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Coimbra, Portugal, 3004-561
- Site 182
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Lisbon, Portugal, 1998-018
- Site 183
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Portimão, Portugal, 8500-338
- Site 197
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Porto, Portugal, 4200-072
- Site 185
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Busan, South Korea, 48108
- Site 161
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Busan, South Korea, 49267
- Site 215
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Goyang-si, South Korea, 10408
- Site 13
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Hwasun, South Korea, 58128
- Site 29
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Seongnam-si, South Korea, 13620
- Site 206
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Seoul, South Korea, 03080
- Site 137
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Seoul, South Korea, 05505
- Site 36
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Seoul, South Korea, 06351
- Site 47
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Seoul, South Korea, 07061
- Site 208
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Soeul, South Korea, 03722
- Site 33
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Suwon, South Korea, 16499
- Site 164
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Barcelona, Spain, 08035
- Site 78
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Madrid, Spain, 28040
- Site 109
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Madrid, Spain, 28040
- Site 75
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Madrid, Spain, 28041
- Site 71
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Madrid, Spain, 28050
- Site 166
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Pamplona, Spain, 31008
- Site 63
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Pamplona, Spain, 31008
- Site 64
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Valencia, Spain, 46009
- Site 74
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Bellinzona, Switzerland, CH-6500
- Site 184
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Geneva, Switzerland, 1211
- Site 189
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Lausanne, Switzerland, 1011
- Site 194
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Sankt Gallen, Switzerland, 9007
- Site 178
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Kaohsiung City, Taiwan, 807
- Site 17
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Kaohsiung City, Taiwan, 833
- Site 95
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Taichung, Taiwan, 40447
- Site 53
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Tainan, Taiwan, 70428
- Site 176
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Taipei, Taiwan, 100
- Site 39
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Taipei, Taiwan, 112
- Site 35
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Taoyuan City, Taiwan, 333
- Site 52
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Cambridge, United Kingdom, CB2 0QQ
- Site 65
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Cardiff, United Kingdom, CF14 2TL
- Site 174
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Glasgow, United Kingdom, G12 0YN
- Site 171
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Liverpool, United Kingdom, L7 8YA
- Site 44
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London, United Kingdom, E20 1JQ
- Site 157
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London, United Kingdom, EC1A 7BE
- Site 140
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London, United Kingdom, SE1 9RT
- Site 90
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London, United Kingdom, SW3 6JJ
- Site 42
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Manchester, United Kingdom, M20 4BX
- Site 48
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Middlesex, United Kingdom, HA6 2RN
- Site 70
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Newcastle upon Tyne, United Kingdom, NE7 7DN
- Site 191
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Sutton, United Kingdom, SM2 5PT
- Site 43
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Alabama
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Mobile, Alabama, United States, 36608
- Site 160
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Arizona
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Prescott, Arizona, United States, 86301
- Site 102
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Scottsdale, Arizona, United States, 85054
- Site 125
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California
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Duarte, California, United States, 91010
- Site 82
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La Jolla, California, United States, 92037
- Site 25
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Orange, California, United States, 92868
- Site 173
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Palo Alto, California, United States, 94304
- Site 28
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Sacramento, California, United States, 95817
- Site 127
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San Francisco, California, United States, 94158
- Site 46
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Colorado
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Lone Tree, Colorado, United States, 80124
- Site 130
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District of Columbia
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Washington D.C., District of Columbia, United States, 20010
- Site 104
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Florida
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Fort Myers, Florida, United States, 33901
- Site 12
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Jacksonville, Florida, United States, 32224
- Site 123
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Orlando, Florida, United States, 32827
- Site 9
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Tampa, Florida, United States, 33612
- Site 138
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Georgia
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Atlanta, Georgia, United States, 30322
- Site 187
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Atlanta, Georgia, United States, 30341
- Site 207
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Illinois
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Chicago, Illinois, United States, 60607
- Site 152
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Chicago, Illinois, United States, 60611
- Site 213
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Chicago, Illinois, United States, 60637
- Site 68
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Indiana
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Indianapolis, Indiana, United States, 46202
- Site 31
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Kentucky
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Louisville, Kentucky, United States, 40202
- Site 8
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Louisiana
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Baton Rouge, Louisiana, United States, 70809
- Site 40
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New Orleans, Louisiana, United States, 70121
- Site 100
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Maryland
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Columbia, Maryland, United States, 21044
- Site 153
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Site 77
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Michigan
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Ann Arbor, Michigan, United States, 48109
- Site 103
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Detroit, Michigan, United States, 48201
- Site 5
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Minnesota
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Maple Grove, Minnesota, United States, 55369
- Site 49
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Rochester, Minnesota, United States, 55905
- Site 124
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Missouri
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St Louis, Missouri, United States, 63110
- Site 18
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New Jersey
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Hackensack, New Jersey, United States, 07601
- Site 86
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New Mexico
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Albuquerque, New Mexico, United States, 87131
- Site 15
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New York
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New York, New York, United States, 10029
- Site 24
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The Bronx, New York, United States, 10461
- Site 214
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North Carolina
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Chapel Hill, North Carolina, United States, 27514
- Site 98
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Durham, North Carolina, United States, 27710
- Site 122
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Ohio
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Cincinnati, Ohio, United States, 45219
- Site 23
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Cleveland, Ohio, United States, 44106
- Site 218
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Cleveland, Ohio, United States, 44195
- Site 87
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Columbus, Ohio, United States, 43210
- Site 32
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Oregon
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Portland, Oregon, United States, 97213
- Site 26
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Pennsylvania
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Bensalem, Pennsylvania, United States, 19020
- Site 151
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Philadelphia, Pennsylvania, United States, 19107
- Site 158
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Philadelphia, Pennsylvania, United States, 19114
- Site 159
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South Carolina
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Charleston, South Carolina, United States, 29425
- Site 50
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Tennessee
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Chattanooga, Tennessee, United States, 37404
- Site 60
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Memphis, Tennessee, United States, 38103
- Site 54
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Nashville, Tennessee, United States, 37203
- Site 59
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Nashville, Tennessee, United States, 37232
- Site 67
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Texas
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Denison, Texas, United States, 75020
- Site 55
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El Paso, Texas, United States, 79915
- Site 34
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Houston, Texas, United States, 77030
- Site 51
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Houston, Texas, United States, 77030
- Site 7
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Pearland, Texas, United States, 77584
- Site 94
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Utah
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Salt Lake City, Utah, United States, 84112
- Site 4
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Virginia
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Blacksburg, Virginia, United States, 24060
- Site 10
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Charlottesville, Virginia, United States, 22908
- Site 22
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Winchester, Virginia, United States, 22601
- Site 156
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Washington
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Seattle, Washington, United States, 98109
- Site 163
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Spokane, Washington, United States, 99202
- Site 6
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Wisconsin
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Madison, Wisconsin, United States, 53705
- Site 216
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Description
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 participants 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.
- A baseline new tumor sample unless the participant 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 prior to randomization.
- Known leptomeningeal involvement
- Any systemic anticancer therapy within 4 weeks prior to randomization.
- Major surgery within 3 weeks or palliative radiotherapy within 2 weeks prior to randomization.
- 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 localized cancer with curative resection (e.g. cervical intraepithelial neoplasia or nonmelanoma skin 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
- Participants with known infectious diseases (as per protocol)
- Pregnant or breastfeeding participants
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Active Comparator: Investigator's Choice
|
Cetuximab
Methotrexate
Docetaxel
|
|
Experimental: MCLA-158
|
MCLA-158
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Overall Survival (OS)
Time Frame: Up to approximately 3 years
|
OS was defined as the time from randomization to death due to any cause.
|
Up to approximately 3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review
Time Frame: Up to approximately 2 years
|
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
|
|
Progression Free Survival (PFS) as Assessed by Blinded Independent Central Review
Time Frame: Up to approximately 2 years
|
PFS was defined as the time from randomization to the first documented disease progression per RECIST v1.1 or death due to any cause.
|
Up to approximately 2 years
|
|
Duration of Response (DOR) as Assessed by Blinded Independent Central Review
Time Frame: Up to approximately 2 years
|
For participants with a confirmed CR or PR per RECIST v1.1, DOR was defined as the time from the date of first documented response of CR or PR per RECIST v1.1 to the date of first documented progression or death due to underlying cancer.
|
Up to approximately 2 years
|
|
Objective Response Rate (ORR) as Assessed by Investigator Review
Time Frame: Up to approximately 2 years
|
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
|
|
Progression Free Survival (PFS) as Assessed by Investigator Review
Time Frame: Up to approximately 2 years
|
PFS was defined as the time from randomization to the first documented disease progression per RECIST v1.1 or death due to any cause.
|
Up to approximately 2 years
|
|
Duration of Response (DOR) as Assessed by Investigator Review
Time Frame: Up to approximately 2 years
|
For participants with a confirmed CR or PR per RECIST v1.1, DOR was defined as the time from the date of the first documented response of CR or PR per RECIST v1.1 to the date of first documented progression or death due to underlying cancer.
|
Up to approximately 2 years
|
|
Time to Response (TTR) as Assessed by Blinded Independent Central Review
Time Frame: Up to approximately 2 years
|
For participants with a confirmed CR or PR per RECIST v1.1, TTR was defined as the time from randomization to the first documented response per RECIST v1.1.
|
Up to approximately 2 years
|
|
Time to Response (TTR) as Assessed by Investigator Review
Time Frame: Up to approximately 2 years
|
For participants with a confirmed CR or PR per RECIST v1.1, TTR was defined as the time from randomization to the first documented response per RECIST v1.1.
|
Up to approximately 2 years
|
|
Clinical Benefit Rate (CBR) as Assessed by Blinded Independent Central Review
Time Frame: Up to approximately 2 years
|
CBR was defined as the proportion of participants with a confirmed CR or PR, or SD lasting 16 weeks for longer per RECIST v1.1
|
Up to approximately 2 years
|
|
Clinical Benefit Rate (CBR) as Assessed by Investigator Review
Time Frame: Up to approximately 2 years
|
CBR was defined as the proportion of participants with a confirmed CR or PR, or SD lasting 16 weeks for longer per RECIST v1.1
|
Up to approximately 2 years
|
|
Pharmacokinetic parameters
Time Frame: Up to first 6 cycles
|
Clearance of plasma and central volume of distribution based on population PK model
|
Up to first 6 cycles
|
|
Number of Participants who Experienced At Least One Treatment Emergent Adverse Event (TEAE)
Time Frame: Up to 30 days post-last dose
|
An AE means any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug related.
The term TEAE covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation after the first treatment administration in the clinical study.
The number of all participants who experienced at least one TEAE is presented.
|
Up to 30 days post-last dose
|
|
Number of Participants who Experienced At Least One Serious TEAE
Time Frame: Up to 30 days post-last dose
|
An AE means any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug related.
The term TEAE covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation after the first treatment administration in the clinical study.
The number of all participants who experienced at least one serious TEAE is presented.
|
Up to 30 days post-last dose
|
|
Number of Participants who Discontinued Study Treatment Due to TEAEs
Time Frame: Up to 30 days post-last dose
|
An AE means any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug related.
The term TEAE covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation after the first treatment administration in the clinical study.
The number of all participants who discontinued study treatment due to TEAEs is presented.
|
Up to 30 days post-last dose
|
|
Number of Participants who had Dose Modification Due to TEAEs
Time Frame: Up to 30 days post-last dose
|
An AE means any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug related.
The term TEAE covers any unfavorable and unintended sign, symptom, syndrome, or illness that develops or worsens during the period of observation after the first treatment administration in the clinical study.
The number of all participants who had dose modification due to TEAEs is presented.
|
Up to 30 days post-last dose
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 25, 2024
Primary Completion (Estimated)
February 1, 2028
Study Completion (Estimated)
March 1, 2029
Study Registration Dates
First Submitted
July 3, 2024
First Submitted That Met QC Criteria
July 3, 2024
First Posted (Actual)
July 11, 2024
Study Record Updates
Last Update Posted (Actual)
August 31, 2026
Last Update Submitted That Met QC Criteria
August 27, 2026
Last Verified
August 1, 2026
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- MCLA-158-CL02
- 2023 (U.S. NIH Grant/Contract: GRAMMY Museum Foundation)
- 2023-510322-32-00 (Ctis)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.