A Phase 3 Study to Evaluate Petosemtamab Compared With Investigator's Choice Monotherapy in Previously Treated Head and Neck Squamous Cell Carcinoma Patients
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Interventions
- Drug: Investigator's Choice
- Registration Number
- NCT06496178
- Lead Sponsor
- Merus N.V.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 500
- 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)
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MCLA-158 Petosemtamab - Investigator's Choice Investigator's Choice -
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Up to approximately 3 years OS was defined as the time from randomization to death due to any cause.
Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review 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.
- Secondary Outcome Measures
Name Time Method Clinical Benefit Rate (CBR) as Assessed by Blinded Independent Central Review 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
Clinical Benefit Rate (CBR) as Assessed by Investigator Review 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
Objective Response Rate (ORR) as Assessed by Investigator Review 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.
Time to Response (TTR) as Assessed by Blinded Independent Central Review 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.
Time to Response (TTR) as Assessed by Investigator Review 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.
Progression Free Survival (PFS) as Assessed by Blinded Independent Central Review 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.
Duration of Response (DOR) as Assessed by Blinded Independent Central Review 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.
Progression Free Survival (PFS) as Assessed by Investigator Review 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.
Duration of Response (DOR) as Assessed by Investigator Review 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.
Number of participants Who experienced At Least One Treatment Emergent Adverse Event (TEAE) 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.
Number of participants Who experienced At Least One Serious TEAE 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.
Number of participants Who Discontinued Study Treatment Due to TEAEs 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.
Number of participants Who Had Dose Modification Due to TEAEs 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.
Pharmacokinetic parameters Up to first 6 cycles Clearance of plasma and central volume of distribution based on population PK model
Incidence of anti-drug antibody (ADA) Up to 30 days post-last dose The frequency and proportion of participants developing anti-drug antibodies.
Mean Change From Baseline in EORTC QLQ-C30 Up to approximately 2 years For the EORTC QLQ-C30, the functional scales, the symptom scales, the specific single items, and the global health and quality of life scale, will be computed according to EORTC QLQ-C30 Scoring Manual. Mean change from baseline is presented.
Mean Change From Baseline in EORTC QLQ-H&N43 Up to approximately 2 years For the updated EORTC QLQ-H\&N43, the multi-item scales and the single-items will be computed according to EORTC QLW-HN43 Scoring Manual. Mean change from baseline is presented.
Concentrations Predose And at End of Infusion Up to first 6 cycles Predose and end of infusion plasma concentrations as measured from all individual plasma concentrations.
Trial Locations
- Locations (129)
Site 56
🇧🇪Brussel, Belgium
Site 92
🇧🇪Gent, Belgium
Site 72
🇧🇪Leuven, Belgium
Site 108
🇧🇪Liège, Belgium
Site 69
🇧🇪Namur, Belgium
Site 16
🇨🇱Providencia, Chile
Site 20
🇨🇱Recoleta, Chile
Site 27
🇨🇱Santiago, Chile
Site 21
🇨🇱Santiago, Chile
Site 105
🇫🇷Bordeaux, France
Site 118
🇫🇷Lyon, France
Site 115
🇫🇷Marseille, France
Site 106
🇫🇷Montpellier, France
Site 65
🇬🇧Cambridge, United Kingdom
Site 114
🇫🇷Paris, France
Site 107
🇫🇷Rouen, France
Site 119
🇫🇷Toulouse, France
Site 113
🇫🇷Villejuif, France
Site 101
🇩🇪Aachen, Germany
Site 121
🇩🇪Berlin, Germany
Site 84
🇩🇪Gießen, Germany
Site 62
🇩🇪Greifswald, Germany
Site 79
🇩🇪Hamburg, Germany
Site 88
🇩🇪Hamburg, Germany
Site 112
🇩🇪Hannover, Germany
Site 116
🇩🇪Leipzig, Germany
Site 99
🇩🇪Würzburg, Germany
Site 91
🇬🇷Athens, Greece
Site 96
🇬🇷Athens, Greece
Site 120
🇬🇷Heraklion, Greece
Site 126
🇬🇷Río, Greece
Site 83
🇬🇷Thessaloníki, Greece
Site 19
🇮🇱Haifa, Israel
Site 1
🇮🇱Jerusalem, Israel
Site 2
🇮🇱Tel Aviv, Israel
Site 14
🇮🇱Tel HaShomer, Israel
Site 93
🇮🇹Brescia, Italy
Site 111
🇮🇹Cuneo, Italy
Site 128
🇮🇹Milano, Italy
Site 81
🇮🇹Milano, Italy
Site 89
🇮🇹Napoli, Italy
Site 85
🇮🇹Rozzano, Italy
Site 13
🇰🇷Goyang-si, Korea, Republic of
Site 29
🇰🇷Hwasun, Korea, Republic of
Site 36
🇰🇷Seoul, Korea, Republic of
Site 47
🇰🇷Seoul, Korea, Republic of
Site 33
🇰🇷Soeul, Korea, Republic of
Site 76
🇳🇱Amsterdam, Netherlands
Site 61
🇳🇱Nijmegen, Netherlands
Site 66
🇳🇱Utrecht, Netherlands
Site 97
🇵🇱Gliwice, Poland
Site 117
🇵🇱Skorzewo, Poland
Site 78
🇪🇸Barcelona, Spain
Site 109
🇪🇸Madrid, Spain
Site 75
🇪🇸Madrid, Spain
Site 71
🇪🇸Madrid, Spain
Site 63
🇪🇸Pamplona, Spain
Site 64
🇪🇸Pamplona, Spain
Site 74
🇪🇸Valencia, Spain
Site 41
🇨🇳Changhua, Taiwan
Site 95
🇨🇳Kaohsiung City, Taiwan
Site 17
🇨🇳Kaohsiung, Taiwan
Site 53
🇨🇳Taichung, Taiwan
Site 35
🇨🇳Taipei City, Taiwan
Site 39
🇨🇳Taipei, Taiwan
Site 52
🇨🇳Taoyuan City, Taiwan
Site 44
🇬🇧Liverpool, United Kingdom
Site 90
🇬🇧London, United Kingdom
Site 42
🇬🇧London, United Kingdom
Site 48
🇬🇧Manchester, United Kingdom
Site 70
🇬🇧Middlesex, United Kingdom
Site 43
🇬🇧Sutton, United Kingdom
Site 102
🇺🇸Prescott, Arizona, United States
Site 73
🇦🇺Sydney, Australia
Site 125
🇺🇸Scottsdale, Arizona, United States
Site 82
🇺🇸Duarte, California, United States
Site 25
🇺🇸La Jolla, California, United States
Site 28
🇺🇸Palo Alto, California, United States
Site 127
🇺🇸Sacramento, California, United States
Site 46
🇺🇸San Francisco, California, United States
Site 104
🇺🇸Washington, District of Columbia, United States
Site 12
🇺🇸Fort Myers, Florida, United States
Site 123
🇺🇸Jacksonville, Florida, United States
Site 9
🇺🇸Orlando, Florida, United States
Site 68
🇺🇸Chicago, Illinois, United States
Site 31
🇺🇸Indianapolis, Indiana, United States
Site 8
🇺🇸Louisville, Kentucky, United States
Site 40
🇺🇸Baton Rouge, Louisiana, United States
Site 100
🇺🇸New Orleans, Louisiana, United States
Site 77
🇺🇸Boston, Massachusetts, United States
Site 103
🇺🇸Ann Arbor, Michigan, United States
Site 5
🇺🇸Detroit, Michigan, United States
Site 49
🇺🇸Maple Grove, Minnesota, United States
Site 124
🇺🇸Rochester, Minnesota, United States
Site 18
🇺🇸Saint Louis, Missouri, United States
Site 86
🇺🇸Hackensack, New Jersey, United States
Site 15
🇺🇸Albuquerque, New Mexico, United States
Site 24
🇺🇸New York, New York, United States
Site 98
🇺🇸Chapel Hill, North Carolina, United States
Site 122
🇺🇸Durham, North Carolina, United States
Site 129
🇧🇪Brussels, Belgium
Site 23
🇺🇸Cincinnati, Ohio, United States
Site 87
🇺🇸Cleveland, Ohio, United States
Site 32
🇺🇸Columbus, Ohio, United States
Site 26
🇺🇸Portland, Oregon, United States
Site 50
🇺🇸Charleston, South Carolina, United States
Site 60
🇺🇸Chattanooga, Tennessee, United States
Site 54
🇺🇸Memphis, Tennessee, United States
Site 59
🇺🇸Nashville, Tennessee, United States
Site 67
🇺🇸Nashville, Tennessee, United States
Site 55
🇺🇸Denison, Texas, United States
Site 34
🇺🇸El Paso, Texas, United States
Site 51
🇺🇸Houston, Texas, United States
Site 7
🇺🇸Houston, Texas, United States
Site 94
🇺🇸Pearland, Texas, United States
Site 4
🇺🇸Salt Lake City, Utah, United States
Site 10
🇺🇸Blacksburg, Virginia, United States
Site 22
🇺🇸Charlottesville, Virginia, United States
Site 6
🇺🇸Spokane, Washington, United States
Site 37
🇦🇷Buenos Aires, Argentina
Site 58
🇦🇷Caba, Argentina
Site 80
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
Site 45
🇦🇷Córdoba, Argentina
Site 110
🇦🇷Rosario, Argentina
Site 57
🇦🇷Viedma, Argentina
Site 3
🇦🇺Darlinghurst, Australia
Site 38
🇦🇺Melbourne, Australia
Site 30
🇦🇺Nedlands, Australia
Site 11
🇦🇺Saint Leonards, Australia