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.
Brief Title
A Phase 3 Study to Evaluate Petosemtamab Compared With Investigator's Choice Monotherapy in Previously Treated Head and Neck Squamous Cell Carcinoma Patients (LiGeR-HN2)
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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
+1 617 401 4499
Central Contact Email
USenquiries@merus.nl
Central Contact Role
Contact
Central Contact Phone
+1 617 401 4499
Central Contact Email
USenquiries@merus.nl
Completion Date
Completion Date Type
Estimated
Conditions
Head and Neck Squamous Cell Carcinoma
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 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.
* Documentation of p16 status (positive or negative) by local laboratory IHC for participants with primary oropharyngeal cancer.
* 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
* Participant has a primary tumor site of nasopharynx (any histology).
* 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.
* Documentation of p16 status (positive or negative) by local laboratory IHC for participants with primary oropharyngeal cancer.
* 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
* Participant has a primary tumor site of nasopharynx (any histology).
Inclusion 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 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.
* Documentation of p16 status (positive or negative) by local laboratory IHC for participants with primary oropharyngeal cancer.
* 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)
* 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.
* Documentation of p16 status (positive or negative) by local laboratory IHC for participants with primary oropharyngeal cancer.
* 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)
Gender
All
Gender Based
false
Keywords
HNSCC
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT06496178
Org Class
Industry
Org Full Name
Merus B.V.
Org Study Id
MCLA-158-CL02
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
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
Primary Outcomes
Outcome Description
OS was defined as the time from randomization to death due to any cause.
Outcome Measure
Overall Survival (OS)
Outcome Time Frame
Up to approximately 3 years
Secondary Ids
Secondary Id
2023-510322-32-00
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review
Outcome Description
PFS was defined as the time from randomization to the first documented disease progression per RECIST v1.1 or death due to any cause.
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Progression Free Survival (PFS) as Assessed by Blinded Independent Central Review
Outcome Description
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.
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Duration of Response (DOR) as Assessed by Blinded Independent Central Review
Outcome Description
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.
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Objective Response Rate (ORR) as Assessed by Investigator Review
Outcome Description
PFS was defined as the time from randomization to the first documented disease progression per RECIST v1.1 or death due to any cause.
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Progression Free Survival (PFS) as Assessed by Investigator Review
Outcome Description
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.
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Duration of Response (DOR) as Assessed by Investigator Review
Outcome Description
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.
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Time to Response (TTR) as Assessed by Blinded Independent Central Review
Outcome Description
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.
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Time to Response (TTR) as Assessed by Investigator Review
Outcome Description
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
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Clinical Benefit Rate (CBR) as Assessed by Blinded Independent Central Review
Outcome Description
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
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Clinical Benefit Rate (CBR) as Assessed by Investigator Review
Outcome Description
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.
Outcome Time Frame
Up to 30 days post-last dose
Outcome Measure
Number of Participants who Experienced At Least One Treatment Emergent Adverse Event (TEAE)
Outcome Description
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.
Outcome Time Frame
Up to 30 days post-last dose
Outcome Measure
Number of Participants who Experienced At Least One Serious TEAE
Outcome Description
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.
Outcome Time Frame
Up to 30 days post-last dose
Outcome Measure
Number of Participants who Discontinued Study Treatment Due to TEAEs
Outcome Description
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.
Outcome Time Frame
Up to 30 days post-last dose
Outcome Measure
Number of Participants who had Dose Modification Due to TEAEs
Outcome Description
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.
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Mean Change From Baseline in EORTC QLQ-C30
Outcome Description
For the 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.
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Mean Change From Baseline in EORTC QLQ-H&N43
Outcome Description
For the EuroQol EQ-5D-5L, the 5 domains and the visual analog scale will be summarized. Mean change from baseline will be presented.
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Mean Change From Baseline in EuroQol EQ-5D-5L
Outcome Description
For the PGIC scale, overall improvement since beginning treatment will be summarized.
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Scores in the Patient Global Impression of Change (PGIC) scale
Outcome Description
Predose and end of infusion plasma concentrations as measured from all individual plasma concentrations.
Outcome Time Frame
Up to first 6 cycles
Outcome Measure
Concentrations Predose and at End of Infusion
Outcome Description
Clearance of plasma and central volume of distribution based on population PK model
Outcome Time Frame
Up to first 6 cycles
Outcome Measure
Pharmacokinetic parameters
Outcome Description
The frequency and proportion of participants developing anti-drug antibodies.
Outcome Time Frame
Up to 30 days post-last dose
Outcome Measure
Incidence of anti-drug antibody (ADA)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Enrico Castellucci
Investigator Email
ecastell@montefiore.org
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Cancer --- CARCINOMA
Cancer --- NEOPLASMS
Cancer --- NEOPLASMS BY SITE
MeSH Terms
SQUAMOUS CELL CARCINOMA OF HEAD AND NECK
CARCINOMA, SQUAMOUS CELL
CARCINOMA
NEOPLASMS, GLANDULAR AND EPITHELIAL
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
HEAD AND NECK NEOPLASMS
NEOPLASMS BY SITE