Head and Neck Squamous Cell Carcinoma
Conditions
Keywords
HNSCC
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.
Interventions
DRUGPetosemtamab
MCLA-158
Cetuximab
Sponsors
Merus B.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to approximately 3 years | OS was defined as the time from randomization to death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 |
| 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 |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, Czechia, France, Germany, Greece, Hungary, Israel, Italy, Japan, Lithuania, Netherlands, Poland, Portugal, South Korea, Spain, Switzerland, Taiwan, United Kingdom, United States
Outcome results
None listed