Clinical trial NCT06496178: A Phase 3 Study to Evaluate Petosemtamab Compared With Investigator's Choice Monotherapy in Previously Treated Head and Neck Squamous Cell Carcinoma Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Head and Neck Squamous Cell Carcinoma
Keywords: HNSCC
Lead sponsor: Merus N.V.
Sponsor class: INDUSTRY
First posted: 2024-07-11
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 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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review
timeFrame: Up to approximately 2 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 3 years
Secondary outcomes:
measure: Progression Free Survival (PFS) as Assessed by Blinded Independent Central Review
timeFrame: Up to approximately 2 years
measure: Duration of Response (DOR) as Assessed by Blinded Independent Central Review
timeFrame: Up to approximately 2 years
measure: Objective Response Rate (ORR) as Assessed by Investigator Review
timeFrame: Up to approximately 2 years
measure: Progression Free Survival (PFS) as Assessed by Investigator Review
timeFrame: Up to approximately 2 years
measure: Duration of Response (DOR) as Assessed by Investigator Review
timeFrame: Up to approximately 2 years
measure: Time to Response (TTR) as Assessed by Blinded Independent Central Review
timeFrame: Up to approximately 2 years
measure: Time to Response (TTR) as Assessed by Investigator Review
timeFrame: Up to approximately 2 years
measure: Clinical Benefit Rate (CBR) as Assessed by Blinded Independent Central Review
timeFrame: Up to approximately 2 years
measure: Clinical Benefit Rate (CBR) 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: Mean Change From Baseline in EORTC QLQ-C30
timeFrame: Up to approximately 2 years
measure: Mean Change From Baseline in EORTC QLQ-H&N43
timeFrame: Up to approximately 2 years
measure: Concentrations Predose And at End of Infusion
timeFrame: Up to first 6 cycles
measure: Pharmacokinetic parameters
timeFrame: Up to first 6 cycles
measure: Incidence of anti-drug antibody (ADA)
timeFrame: Up to 30 days post-last dose
Other outcomes:
Locations:
city: Prescott
country: United States
facility: Site 102
state: Arizona
city: Scottsdale
country: United States
facility: Site 125
state: Arizona
city: Duarte
country: United States
facility: Site 82
state: California
city: La Jolla
country: United States
facility: Site 25
state: California
city: Palo Alto
country: United States
facility: Site 28
state: California
city: Sacramento
country: United States
facility: Site 127
state: California
city: San Francisco
country: United States
facility: Site 46
state: California
city: Lone Tree
country: United States
facility: Site 130
state: Colorado
city: Washington
country: United States
facility: Site 104
state: District of Columbia
city: Fort Myers
country: United States
facility: Site 12
state: Florida
city: Jacksonville
country: United States
facility: Site 123
state: Florida
city: Orlando
country: United States
facility: Site 9
state: Florida
city: Chicago
country: United States
facility: Site 68
state: Illinois
city: Indianapolis
country: United States
facility: Site 31
state: Indiana
city: Louisville
country: United States
facility: Site 8
state: Kentucky
city: Baton Rouge
country: United States
facility: Site 40
state: Louisiana
city: New Orleans
country: United States
facility: Site 100
state: Louisiana
city: Boston
country: United States
facility: Site 77
state: Massachusetts
city: Ann Arbor
country: United States
facility: Site 103
state: Michigan
city: Detroit
country: United States
facility: Site 5
state: Michigan
city: Maple Grove
country: United States
facility: Site 49
state: Minnesota
city: Rochester
country: United States
facility: Site 124
state: Minnesota
city: Saint Louis
country: United States
facility: Site 18
state: Missouri
city: Hackensack
country: United States
facility: Site 86
state: New Jersey
city: Albuquerque
country: United States
facility: Site 15
state: New Mexico
city: New York
country: United States
facility: Site 24
state: New York
city: Chapel Hill
country: United States
facility: Site 98
state: North Carolina
city: Durham
country: United States
facility: Site 122
state: North Carolina
city: Cincinnati
country: United States
facility: Site 23
state: Ohio
city: Cleveland
country: United States
facility: Site 87
state: Ohio
city: Columbus
country: United States
facility: Site 32
state: Ohio
city: Portland
country: United States
facility: Site 26
state: Oregon
city: Charleston
country: United States
facility: Site 50
state: South Carolina
city: Chattanooga
country: United States
facility: Site 60
state: Tennessee
city: Memphis
country: United States
facility: Site 54
state: Tennessee
city: Nashville
country: United States
facility: Site 59
state: Tennessee
city: Nashville
country: United States
facility: Site 67
state: Tennessee
city: Denison
country: United States
facility: Site 55
state: Texas
city: El Paso
country: United States
facility: Site 34
state: Texas
city: Houston
country: United States
facility: Site 51
state: Texas
city: Houston
country: United States
facility: Site 7
state: Texas
city: Pearland
country: United States
facility: Site 94
state: Texas
city: Salt Lake City
country: United States
facility: Site 4
state: Utah
city: Blacksburg
country: United States
facility: Site 10
state: Virginia
city: Charlottesville
country: United States
facility: Site 22
state: Virginia
city: Spokane
country: United States
facility: Site 6
state: Washington
city: Buenos Aires
country: Argentina
facility: Site 37
city: Caba
country: Argentina
facility: Site 58
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Site 80
city: Córdoba
country: Argentina
facility: Site 45
city: Rosario
country: Argentina
facility: Site 110
city: Viedma
country: Argentina
facility: Site 57
city: Darlinghurst
country: Australia
facility: Site 3
city: Melbourne
country: Australia
facility: Site 38
city: Nedlands
country: Australia
facility: Site 30
city: Saint Leonards
country: Australia
facility: Site 11
city: Sydney
country: Australia
facility: Site 73
city: Brussels
country: Belgium
facility: Site 129
city: Brussel
country: Belgium
facility: Site 56
city: Gent
country: Belgium
facility: Site 92
city: Leuven
country: Belgium
facility: Site 72
city: Liège
country: Belgium
facility: Site 108
city: Namur
country: Belgium
facility: Site 69
city: Providencia
country: Chile
facility: Site 16
city: Recoleta
country: Chile
facility: Site 20
city: Santiago
country: Chile
facility: Site 27
city: Santiago
country: Chile
facility: Site 21
city: Bordeaux
country: France
facility: Site 105
city: Lyon
country: France
facility: Site 118
city: Marseille
country: France
facility: Site 115
city: Montpellier
country: France
facility: Site 106
city: Paris
country: France
facility: Site 114
city: Poitiers
country: France
facility: Site 136
city: Rouen
country: France
facility: Site 107
city: Toulouse
country: France
facility: Site 119
city: Villejuif
country: France
facility: Site 113
city: Aachen
country: Germany
facility: Site 101
city: Berlin
country: Germany
facility: Site 121
city: Gießen
country: Germany
facility: Site 84
city: Greifswald
country: Germany
facility: Site 62
city: Hamburg
country: Germany
facility: Site 79
city: Hamburg
country: Germany
facility: Site 88
city: Hannover
country: Germany
facility: Site 112
city: Leipzig
country: Germany
facility: Site 116
city: Würzburg
country: Germany
facility: Site 99
city: Athens
country: Greece
facility: Site 91
city: Athens
country: Greece
facility: Site 96
city: Heraklion
country: Greece
facility: Site 120
city: Río
country: Greece
facility: Site 126
city: Thessaloníki
country: Greece
facility: Site 83
city: Haifa
country: Israel
facility: Site 19
city: Jerusalem
country: Israel
facility: Site 1
city: Tel Aviv
country: Israel
facility: Site 2
city: Tel HaShomer
country: Israel
facility: Site 14
city: Brescia
country: Italy
facility: Site 93
city: Cuneo
country: Italy
facility: Site 111
city: Milano
country: Italy
facility: Site 128
city: Milano
country: Italy
facility: Site 81
city: Napoli
country: Italy
facility: Site 89
city: Rozzano
country: Italy
facility: Site 85
city: Chuo Ku
country: Japan
facility: Site 132
city: Kashiwa
country: Japan
facility: Site 131
city: Miki
country: Japan
facility: Site 135
city: Sendai
country: Japan
facility: Site 134
city: Ōsaka-sayama
country: Japan
facility: Site 133
city: Goyang-si
country: Korea, Republic of
facility: Site 13
city: Hwasun
country: Korea, Republic of
facility: Site 29
city: Seoul
country: Korea, Republic of
facility: Site 137
city: Seoul
country: Korea, Republic of
facility: Site 36
city: Seoul
country: Korea, Republic of
facility: Site 47
city: Soeul
country: Korea, Republic of
facility: Site 33
city: Amsterdam
country: Netherlands
facility: Site 76
city: Nijmegen
country: Netherlands
facility: Site 61
city: Utrecht
country: Netherlands
facility: Site 66
city: Gliwice
country: Poland
facility: Site 97
city: Skorzewo
country: Poland
facility: Site 117
city: Barcelona
country: Spain
facility: Site 78
city: Madrid
country: Spain
facility: Site 109
city: Madrid
country: Spain
facility: Site 75
city: Madrid
country: Spain
facility: Site 71
city: Pamplona
country: Spain
facility: Site 63
city: Pamplona
country: Spain
facility: Site 64
city: Valencia
country: Spain
facility: Site 74
city: Changhua
country: Taiwan
facility: Site 41
city: Kaohsiung City
country: Taiwan
facility: Site 95
city: Kaohsiung
country: Taiwan
facility: Site 17
city: Taichung
country: Taiwan
facility: Site 53
city: Taipei City
country: Taiwan
facility: Site 35
city: Taipei
country: Taiwan
facility: Site 39
city: Taoyuan City
country: Taiwan
facility: Site 52
city: Cambridge
country: United Kingdom
facility: Site 65
city: Liverpool
country: United Kingdom
facility: Site 44
city: London
country: United Kingdom
facility: Site 90
city: London
country: United Kingdom
facility: Site 42
city: Manchester
country: United Kingdom
facility: Site 48
city: Middlesex
country: United Kingdom
facility: Site 70
city: Sutton
country: United Kingdom
facility: Site 43
Study officials:
References: