Clinical trial NCT06525220: A Phase 3 Study to Evaluate Petosemtamab Plus Pembrolizumab vs Pembrolizumab in First-line Treatment of Head and Neck Cancer (LiGeR - HN1)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Head and Neck Squamous Cell Carcinoma
Keywords: HNSCC
PD-L1+
Head and Neck cancer
Petosemtamab
Pembrolizumab
Liger
Oral Cavity
Oropharynx
Larynx
Hypopharynx
Lead sponsor: Merus N.V.
Sponsor class: INDUSTRY
First posted: 2024-07-29
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Other protocol defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 3 years
measure: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by blinded independent central review (BICR)
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Progression Free Survival (PFS) per RECIST v1.1 as assessed by BICR
timeFrame: Up to approximately 2 years
measure: Duration of Response (DOR) per RECIST v1.1 as assessed by BICR
timeFrame: Up to approximately 2 years
measure: Objective response rate per RECIST v1.1 as assessed by investigator review
timeFrame: Up to approximately 2 years
measure: Progression-free survival per RECIST v1.1 as assessed by investigator review
timeFrame: Up to approximately 2 years
measure: Duration of response per RECIST v1.1 as assessed by investigator review
timeFrame: Up to approximately 2 years
measure: Clinical benefit rate per RECIST v1.1 as assessed by BICR
timeFrame: Up to approximately 2 years
measure: Clinical benefit rate per RECIST v1.1 as assessed by investigator review
timeFrame: Up to approximately 2 years
measure: Number of participants who experienced at least one treatment emergent adverse event (TEAE)
timeFrame: Up to 30 days post last dose
measure: Number of participants who experienced at least one serious TEAE
timeFrame: Up to 30 days post last dose
measure: Number of participants who discontinued study treatment due to TEAEs
timeFrame: Up to 30 days post last dose
measure: Number of participants who had dose modification due to TEAEs
timeFrame: Up to 30 days post last dose
measure: To evaluate patient reported outcomes for health-related quality of life
timeFrame: Up to approximately 2 years
measure: Pharmacokinetic parameters
timeFrame: Up to first 6 cycles
measure: Incidence of anti-drug antibodies (ADAs)
timeFrame: Up to 30 days post last dose
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Site 36
state: California
city: Los Angeles
country: United States
facility: Site 27
state: California
city: Palo Alto
country: United States
facility: Site 16
state: California
city: Newark
country: United States
facility: Site 19
state: Delaware
city: Washington
country: United States
facility: Site 108
state: District of Columbia
city: Fort Myers
country: United States
facility: Site 14
state: Florida
city: Orlando
country: United States
facility: Site 48
state: Florida
city: Orlando
country: United States
facility: Site 8
state: Florida
city: Saint Petersburg
country: United States
facility: Site 21
state: Florida
city: West Palm Beach
country: United States
facility: Site 20
state: Florida
city: Chicago
country: United States
facility: Site 50
state: Illinois
city: Louisville
country: United States
facility: Site 2
state: Kentucky
city: Hackensack
country: United States
facility: Site 94
state: New Jersey
city: Albuquerque
country: United States
facility: Site 6
state: New Mexico
city: Durham
country: United States
facility: Site 113
state: North Carolina
city: Winston-Salem
country: United States
facility: Site 118
state: North Carolina
city: Philadelphia
country: United States
facility: Site 43
state: Pennsylvania
city: Chattanooga
country: United States
facility: Site 89
state: Tennessee
city: Memphis
country: United States
facility: Site 115
state: Tennessee
city: Nashville
country: United States
facility: Site 88
state: Tennessee
city: Austin
country: United States
facility: Site 22
state: Texas
city: Houston
country: United States
facility: Site 1
state: Texas
city: Plano
country: United States
facility: Site 18
state: Texas
city: Sugarland
country: United States
facility: Site 17
state: Texas
city: Tyler
country: United States
facility: Site 15
state: Texas
city: Salt Lake City
country: United States
facility: Site 10
state: Utah
city: Blacksburg
country: United States
facility: Site 12
state: Virginia
city: Norfolk
country: United States
facility: Site 23
state: Virginia
city: Caba
country: Argentina
facility: Site 96
city: Caba
country: Argentina
facility: Site 37
city: Córdoba
country: Argentina
facility: Site 31
city: La Rioja
country: Argentina
facility: Site 30
city: Rosario
country: Argentina
facility: Site 76
city: Viedma
country: Argentina
facility: Site 46
city: Blacktown
country: Australia
facility: Site 11
state: New South Wales
city: St Leonards
country: Australia
facility: Site 24
state: New South Wales
city: Brussels
country: Belgium
facility: Site 53
city: Edegem
country: Belgium
facility: Site 98
city: Gent
country: Belgium
facility: Site 99
city: Leuven
country: Belgium
facility: Site 71
city: Liège
country: Belgium
facility: Site 109
city: Namur
country: Belgium
facility: Site 63
city: Toronto
country: Canada
facility: Site 44
city: Winnipeg
country: Canada
facility: Site 111
city: Antofagasta
country: Chile
facility: Site 38
city: Providencia
country: Chile
facility: Site 26
city: Recoleta
country: Chile
facility: Site 29
city: Santiago
country: Chile
facility: Site 40
city: Santiago
country: Chile
facility: Site 32
city: Santiago
country: Chile
facility: Site 34
city: Temuco
country: Chile
facility: Site 25
city: Bordeaux
country: France
facility: Site 56
city: Le Mans
country: France
facility: Site 101
city: Lille
country: France
facility: Site 79
city: Lyon
country: France
facility: Site 72
city: Marseille
country: France
facility: Site 57
city: Montpellier
country: France
facility: Site 55
city: Nice
country: France
facility: Site 66
city: Paris
country: France
facility: Site 105
city: Poitiers
country: France
facility: Site 87
city: Rouen
country: France
facility: Site 54
city: Toulouse
country: France
facility: Site 59
city: Vandœuvre-lès-Nancy
country: France
facility: Site 64
city: Villejuif
country: France
facility: Site 112
city: Dresden
country: Germany
facility: Site 100
city: Greifswald
country: Germany
facility: Site 60
city: Hamburg
country: Germany
facility: Site 82
city: Hamburg
country: Germany
facility: Site 91
city: Hannover
country: Germany
facility: Site 104
city: Mannheim
country: Germany
facility: Site 129
city: Münster
country: Germany
facility: Site 121
city: Tübingen
country: Germany
facility: Site 78
city: Würzburg
country: Germany
facility: Site 110
city: Patras
country: Greece
facility: Site 119
state: Achaia
city: Heraklion
country: Greece
facility: Site 117
state: Crete
city: Chaïdári
country: Greece
facility: Site 95
city: Panórama
country: Greece
facility: Site 92
city: Haifa
country: Israel
facility: Site 9
city: Jerusalem
country: Israel
facility: Site 5
city: Ramat Gan
country: Israel
facility: Site 3
city: Tel Aviv
country: Israel
facility: Site 7
city: Ancona
country: Italy
facility: Site 86
city: Brescia
country: Italy
facility: Site 97
city: Milan
country: Italy
facility: Site 122
city: Milan
country: Italy
facility: Site 81
city: Naples
country: Italy
facility: Site 93
city: Rozzano
country: Italy
facility: Site 85
city: Kashiwa
country: Japan
facility: Site 123
state: Chiba
city: Miki
country: Japan
facility: Site 127
state: Kagawa
city: Sendai
country: Japan
facility: Site 126
state: Miyagi
city: Ōsaka-sayama
country: Japan
facility: Site 125
state: Osaka
city: Chuo Ku
country: Japan
facility: Site 124
state: Tokyo
city: Goyang-si
country: Korea, Republic of
facility: Site 13
city: Gyeonggi-do
country: Korea, Republic of
facility: Site 47
city: Hwasun
country: Korea, Republic of
facility: Site 51
city: Seoul
country: Korea, Republic of
facility: Site 28
city: Seoul
country: Korea, Republic of
facility: Site 35
city: Seoul
country: Korea, Republic of
facility: Site 45
city: Suwon-si
country: Korea, Republic of
facility: Site 42
city: Amsterdam
country: Netherlands
facility: Site 84
city: Nijmegen
country: Netherlands
facility: Site 58
city: Utrecht
country: Netherlands
facility: Site 68
city: Gliwice
country: Poland
facility: Site 106
city: Kraków
country: Poland
facility: Site 116
city: Badalona
country: Spain
facility: Site 120
city: Barcelona
country: Spain
facility: Site 80
city: Madrid
country: Spain
facility: Site 128
city: Madrid
country: Spain
facility: Site 75
city: Madrid
country: Spain
facility: Site 67
city: Marbella
country: Spain
facility: Site 73
city: Pamplona
country: Spain
facility: Site 61
city: Pamplona
country: Spain
facility: Site 62
city: Valencia
country: Spain
facility: Site 74
city: Changhua
country: Taiwan
facility: Site 41
city: Kaohsiung
country: Taiwan
facility: Site 4
city: Kaohsiung
country: Taiwan
facility: Site 103
city: Taichung
country: Taiwan
facility: Site 52
city: Taipei City
country: Taiwan
facility: Site 39
city: Taipei City
country: Taiwan
facility: Site 33
city: Taoyuan City
country: Taiwan
facility: Site 49
city: Bangkok Noi
country: Thailand
facility: Site 114
state: Bangkok
city: Pathum Wan
country: Thailand
facility: Site 107
state: Bangkok
city: Ratchathewi
country: Thailand
facility: Site 65
state: Bangkok
city: Hat Yai
country: Thailand
facility: Site 77
state: Songkhla
city: Cambridge
country: United Kingdom
facility: Site 102
city: London
country: United Kingdom
facility: Site 90
city: London
country: United Kingdom
facility: Site 69
city: Northwood
country: United Kingdom
facility: Site 83
city: Sutton
country: United Kingdom
facility: Site 70
Study officials:
References: