Sponsor: Merus N.V. (industry)
Phase: 3
Start date: June 25, 2024
Planned enrollment: 500
Petosemtamab (MCLA-158) is an investigational bispecific antibody being studied for several advanced cancers. The most substantial reported human results are from single-arm phase 2 studies in recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), both alone after prior treatment and with pembrolizumab as first-line treatment. These studies show antitumor activity but cannot establish how much benefit petosemtamab adds over existing treatments. (annalsofoncology.org)
Petosemtamab binds EGFR and LGR5, a marker found on some stem-like cancer cells. Preclinical research indicates that binding both targets can promote EGFR degradation in LGR5-positive cells, suppress EGFR signaling, and recruit immune cells through antibody-dependent cellular cytotoxicity. Whether these mechanisms account for clinical benefit remains under investigation. (nature.com)
In a previously treated HNSCC cohort, commonly reported adverse events included acneiform dermatitis, decreased magnesium, rash, and infusion-related reactions. In the first-line combination cohort of 45 patients, 27 (60%) had a grade 3 or higher treatment-emergent adverse event, and 20 (44%) had one considered treatment-related. Infusion-related reactions occurred in 38%, including grade 3 reactions in 7%. Adverse-event figures include events not necessarily caused by petosemtamab. (annalsofoncology.org)
Last updated: Sep 2026
Goal: Determine whether petosemtamab improves response and survival compared with investigator’s choice monotherapy as second- or third-line treatment for incurable recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).
Patients: Adults with incurable recurrent or metastatic squamous cell carcinoma of the oropharynx, oral cavity, hypopharynx, or larynx that has progressed on or after anti-PD-1 and platinum-containing therapy. Patients must have measurable disease, ECOG performance status 0–1, and adequate organ function. Oropharyngeal tumors require documented p16 status; nasopharyngeal primary tumors are excluded.
Design: Multicenter, open-label, randomized controlled trial comparing petosemtamab with investigator’s choice monotherapy. Tumor response and progression are assessed by blinded independent central review and by investigators.
Treatments: Patients receive petosemtamab (MCLA-158) or investigator’s choice monotherapy; the comparator drugs are not specified. Petosemtamab is an investigational bispecific antibody targeting EGFR and LGR5, with preclinical evidence of EGFR degradation in LGR5-positive cells and recruitment of immune cells. In a previously treated HNSCC single-arm phase 2 analysis, investigator-assessed responses occurred in 19 of 47 evaluable patients (40.4%), with a median response duration of 7.2 months; comparative benefit remains unproven.
Outcomes: Primary outcomes are confirmed RECIST v1.1 objective response rate by blinded independent central review and overall survival. Secondary outcomes include progression-free survival, response duration, time to response, clinical benefit rate, adverse events and treatment changes due to toxicity, patient-reported quality of life, petosemtamab pharmacokinetics, and anti-drug antibodies.
Burden on patient: Moderate burden is expected from treatment visits, serial imaging, safety assessments, and quality-of-life questionnaires, with survival follow-up lasting up to approximately three years. A baseline tumor sample is required unless sufficient archived tissue is available, so some patients may need a new biopsy. Pharmacokinetic sampling before and at the end of infusions during the first six cycles adds blood draws; treatment and scan schedules are not specified.
Last updated: Sep 2026
Inclusion Criteria:
* Signed ICF before initiation of any study procedures.
* Age ≥ 18 years at signing of ICF.
* Histologically previously confirmed HNSCC with evidence of metastatic or locally advanced disease not amenable to standard therapy with curative intent.
* HNSCC patients progressed on or after anti-PD-1 therapy and platinum-containing therapy.
* The eligible HNSCC primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.
* Documentation of p16 status (positive or negative) by local laboratory IHC for patients with primary oropharyngeal cancer.
* A baseline new tumor sample unless the patient has an available tumor sample as an FFPE block with sufficient material.
* Measurable disease as defined by RECIST v1.1 by radiologic methods.
* ECOG PS of 0 or 1
* Life expectancy ≥ 12 weeks, as per investigator
* Adequate organ function (as per protocol)
Exclusion Criteria:
* Central nervous system metastases that are untreated or symptomatic, or require radiation, surgery, or continued steroid therapy to control symptoms within 14 days of study entry.
* Known leptomeningeal involvement
* Any systemic anticancer therapy within 4 weeks of the first dose of study treatment.
* Major surgery or radiotherapy within 3 weeks of the first dose of study treatment.
* Persistent Grade \>1 clinically significant toxicities related to prior antineoplastic therapies
* History of hypersensitivity reaction to any of the excipients of treatment required for this study.
* Unstable angina; history of congestive heart failure of Class II-IV New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment or history of myocardial infarction within 6 months of study entry
* History of prior malignancies with the exception of excised cervical intraepithelial neoplasia or nonmelanoma skin cancer, or curatively treated cancer deemed at low risk for recurrence with no evidence of disease
* Current dyspnea at rest of any origin, or other diseases requiring continuous oxygen therapy
* Current serious illness or medical conditions including, but not limited to, uncontrolled active infection, clinically significant pulmonary, metabolic or psychiatric disorders
* Patients with known infectious diseases (as per protocol)
* Pregnant or breastfeeding patients
* Patient has a primary tumor site of nasopharynx (any histology).
Rosario, S2000KZE, Argentina
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CABA, Clll3AAE, Argentina
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Córdoba, X5008HHW, Argentina
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Viedma, 8500, Argentina
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Caba, C1280AEB, Argentina
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Saint Leonards, 2065, Australia
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Herston, 4060, Australia
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Darlinghurst, 2010, Australia
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Nedlands, 6009, Australia
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Melbourne, 3000, Australia
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Sydney, 2050, Australia
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Liège, 4000, Belgium
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Brussels, 1200, Belgium
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Namur, 5000, Belgium
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Leuven, 3000, Belgium
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Ghent, 9000, Belgium
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São Paulo, 04538-132, Brazil
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Porto Alegre, 90110-270, Brazil
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Recife, 50040-000, Brazil
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São Paulo, 01509-900, Brazil
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Rio de Janeiro, 22281-100, Brazil
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Porto Alegre, 90610-000, Brazil
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Brasília, 70390-140, Brazil
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Rio de Janeiro, 22.250-905, Brazil
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Montreal, H2X 0A9, Canada
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Toronto, M4N 3M5, Canada
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Providencia, 7500859, Chile
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Recoleta, 8420000, Chile
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Santiago, 7560908, Chile
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Santiago, 7500921, Chile
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Nový Jičín, 74101, Czechia
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Olomouc, 779 00, Czechia
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Prague, 150 06, Czechia
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Bordeaux, 33075, France
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Montpellier, 34298, France
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Rouen, 76038, France
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Villejuif, 94800, France
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Paris, 75005, France
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Marseille, 13005, France
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Lyon, 69373, France
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Toulouse, 31059, France
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Poitiers, 86000, France
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Rennes, 35042, France
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Vandœuvre-lès-Nancy, 54519, France
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Lille, 59000, France
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Le Mans, 72000, France
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Paris, 75013, France
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Nice, 06189, France
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Aachen, 52074, Germany
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Hanover, 30625, Germany
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Leipzig, 04103, Germany
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Berlin, 12203, Germany
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Essen, 45147, Germany
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München, 81675, Germany
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Mannheim, 68167, Germany
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Greifswald, 17475, Germany
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Hamburg, 20246, Germany
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Giessen, 35390, Germany
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Hamburg, 22763, Germany
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Würzburg, 97080, Germany
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Heraklion, 71500, Greece
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Rio, 26504, Greece
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Thessaloniki, 55236, Greece
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Athens, 124 62, Greece
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Athens, 15123, Greece
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Pécs, 7624, Hungary
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Szeged, 6725, Hungary
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Nyíregyháza, 4400, Hungary
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Jerusalem, 9112001, Israel
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Ramat Gan, 5265601, Israel
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Haifa, 3109601, Israel
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Tel Aviv, 6423906, Israel
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Cuneo, 12100, Italy
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Milan, 20133, Italy
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Roma, 00161, Italy
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Milan, 20141, Italy
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Rozzano, 20089, Italy
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Naples, 80131, Italy
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Brescia, 25123, Italy
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Kashiwa, 277-8577, Japan
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Chūōku, 104-0045, Japan
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Ōsaka-sayama, 589-8511, Japan
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Sendai, 980-8574, Japan
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Miki, 761-0793, Japan
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Nagoya, 464-8681, Japan
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Natori, 981-1293, Japan
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Fukuoka, 812-8582, Japan
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Fukuoka, 810-8563, Japan
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Minatoku, 105-8471, Japan
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Kaunas, 50161, Lithuania
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Vilnius, 08406, Lithuania
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Nijmegen, 6525 GA, Netherlands
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Utrecht, 3584 CX, Netherlands
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Amsterdam, 1066 CX, Netherlands
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Poznan, 60-185, Poland
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Gdansk, 80-214, Poland
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Krakow, 31-826, Poland
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Warsaw, 02-781, Poland
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Bydgoszcz, 85-796, Poland
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Lodz, 93-513, Poland
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Gliwice, 44-102, Poland
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Coimbra, 3004-561, Portugal
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Lisbon, 1998-018, Portugal
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Porto, 4200-072, Portugal
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Portimão, 8500-338, Portugal
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Goyang-si, 10408, South Korea
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Seoul, 03080, South Korea
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Busan, 48108, South Korea
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Suwon, 16499, South Korea
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Seongnam-si, 13620, South Korea
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Seoul, 07061, South Korea
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Hwasun, 58128, South Korea
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Soeul, 03722, South Korea
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Seoul, 05505, South Korea
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Seoul, 06351, South Korea
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Madrid, 28040, Spain
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Madrid, 28050, Spain
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Pamplona, 31008, Spain
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Pamplona, 31008, Spain
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Madrid, 28041, Spain
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Valencia, 46009, Spain
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Madrid, 28040, Spain
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Barcelona, 08035, Spain
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Sankt Gallen, 9007, Switzerland
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Bellinzona, CH-6500, Switzerland
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Geneva, 1211, Switzerland
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Lausanne, 1011, Switzerland
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Kaohsiung City, 807, Taiwan
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Tainan, 70428, Taiwan
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Taipei, 112, Taiwan
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Taipei, 100, Taiwan
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Taoyuan, 333, Taiwan
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Taichung, 40447, Taiwan
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Kaohsiung City, 833, Taiwan
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London, EC1A 7BE, United Kingdom
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London, E20 1JQ, United Kingdom
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Glasgow, G12 0YN, United Kingdom
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Cardiff, CF14 2TL, United Kingdom
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Newcastle upon Tyne, NE7 7DN, United Kingdom
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London, SW3 6JJ, United Kingdom
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Sutton, SM2 5PT, United Kingdom
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Liverpool, L7 8YA, United Kingdom
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Manchester, M20 4BX, United Kingdom
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Cambridge, CB2 0QQ, United Kingdom
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Middlesex, HA6 2RN, United Kingdom
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London, SE1 9RT, United Kingdom
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Mobile, Alabama, 36608, United States
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Status: Recruiting
Scottsdale, Arizona, 85054, United States
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Status: Recruiting
Sacramento, California, 95817, United States
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Orange, California, 92868, United States
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La Jolla, California, 92037, United States
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Palo Alto, California, 94304, United States
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San Francisco, California, 94158, United States
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Duarte, California, 91010, United States
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Status: Recruiting
Lone Tree, Colorado, 80124, United States
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Washington D.C., District of Columbia, 20010, United States
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Fort Myers, Florida, 33901, United States
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Jacksonville, Florida, 32224, United States
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Tampa, Florida, 33612, United States
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Orlando, Florida, 32827, United States
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Atlanta, Georgia, 30322, United States
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Atlanta, Georgia, 30341, United States
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Chicago, Illinois, 60607, United States
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Chicago, Illinois, 60637, United States
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Indianapolis, Indiana, 46202, United States
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Louisville, Kentucky, 40202, United States
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New Orleans, Louisiana, 70121, United States
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Baton Rouge, Louisiana, 70809, United States
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Status: Recruiting
Columbia, Maryland, 21044, United States
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Boston, Massachusetts, 02215, United States
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Ann Arbor, Michigan, 48109, United States
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Detroit, Michigan, 48201, United States
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Rochester, Minnesota, 55905, United States
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Maple Grove, Minnesota, 55369, United States
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St Louis, Missouri, 63110, United States
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Hackensack, New Jersey, 07601, United States
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Albuquerque, New Mexico, 87131, United States
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New York, New York, 10029, United States
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Durham, North Carolina, 27710, United States
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Chapel Hill, North Carolina, 27514, United States
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Cincinnati, Ohio, 45219, United States
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Columbus, Ohio, 43210, United States
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Cleveland, Ohio, 44195, United States
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Portland, Oregon, 97213, United States
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Bensalem, Pennsylvania, 19020, United States
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Philadelphia, Pennsylvania, 19107, United States
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Philadelphia, Pennsylvania, 19114, United States
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Charleston, South Carolina, 29425, United States
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Memphis, Tennessee, 38103, United States
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Nashville, Tennessee, 37203, United States
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Chattanooga, Tennessee, 37404, United States
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Nashville, Tennessee, 37232, United States
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El Paso, Texas, 79915, United States
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Houston, Texas, 77030, United States
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Denison, Texas, 75020, United States
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Houston, Texas, 77030, United States
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Pearland, Texas, 77584, United States
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Salt Lake City, Utah, 84112, United States
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Blacksburg, Virginia, 24060, United States
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Winchester, Virginia, 22601, United States
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Charlottesville, Virginia, 22908, United States
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Seattle, Washington, 98109, United States
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Spokane, Washington, 99202, United States
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Status: Recruiting
Prescott, Arizona, 86301, United States
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Status: Completed
Buenos Aires, C1125ABD, Argentina
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Status: Withdrawn
Buenos Aires, C1426ANZ, Argentina
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Status: Withdrawn
Brussels, 1070, Belgium
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Status: Withdrawn
Changhua, 500, Taiwan
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Status: Withdrawn