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 (163)
Site 160
🇺🇸Mobile, Alabama, United States
Site 102
🇺🇸Prescott, Arizona, United States
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 130
🇺🇸Lone Tree, Colorado, United States
Site 104
🇺🇸Washington D.C., District of Columbia, United States
Scroll for more (153 remaining)Site 160🇺🇸Mobile, Alabama, United States