Brief Summary
The purpose of this study is to evaluate the tolerability and safety of Xevinapant when added to weekly cisplatin-based concurrent chemoradiotherapy (CRT) in the treatment of participants with unresectable locally advanced squamous cell carcinoma of the head and neck, suitable for definitive chemoradiotherapy.
Brief Title
Phase 1b Safety Study of Xevinapant, Weekly Cisplatin, and RT in Participants With Unresected LA SCCHN (HyperlynX)
Categories
Completion Date
Completion Date Type
Actual
Conditions
Head and Neck Cancer
Eligibility Criteria
Inclusion Criteria:
* Participants having an Eastern Cooperative Oncology Group Performance Score (ECOG PS) of 0 - 1
* Histologically confirmed diagnosis in previously untreated Locally Advanced Squamous Cell Carcinoma of Head and neck (LA SCCHN) patient (Stage III, IVA, or IVB according to the American Joint Committee on Cancer \[AJCC\]/ Tumor Nodes and metastases (TNM) Staging System, 8th Edition) suitable for definitive Chemoradiotherapy (CRT), with one of the following primary sites: oropharynx (OPC) Human Papillomavirus (HPV)-negative, hypopharynx, and larynx
* Participant should be able to swallow liquids or has an adequately functioning feeding tube, gastrostomy, or jejunostomy in place. For participants requiring liquid nutrition at baseline or during the study including the follow-up period, access to liquid nutrition supply should be ensured
* Participant with evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by CT scan and/or MRI, based on RECIST v 1.1.
* Adequate hematological, hepatic, and renal function as defined in the protocol
* Other protocol defined inclusion criteria could apply
Exclusion Criteria:
* Primary tumor of nasopharyngeal, paranasal sinuses, nasal, or oral cavity, salivary, thyroid, or parathyroid gland pathologies, skin, or unknown primary site
* Metastatic disease (Stage IVC as per AJCC/TNM, 8th Edition)
* Existing need of a hearing aid or greater than or equal to (\>=) 25 decibel shift over 2 contiguous frequencies on a pretreatment hearing test as clinically indicated
* Known history of infection with human immunodeficiency virus (HIV). If unknown history of HIV, an HIV screening test is to be performed and participants with positive serology for HIV-1/2 must be excluded
* Known gastrointestinal disorder with clinically established malabsorption syndrome and major gastrointestinal surgery in the last 12 months that may limit oral absorption
* Other protocol defined exclusion criteria could apply
* Participants having an Eastern Cooperative Oncology Group Performance Score (ECOG PS) of 0 - 1
* Histologically confirmed diagnosis in previously untreated Locally Advanced Squamous Cell Carcinoma of Head and neck (LA SCCHN) patient (Stage III, IVA, or IVB according to the American Joint Committee on Cancer \[AJCC\]/ Tumor Nodes and metastases (TNM) Staging System, 8th Edition) suitable for definitive Chemoradiotherapy (CRT), with one of the following primary sites: oropharynx (OPC) Human Papillomavirus (HPV)-negative, hypopharynx, and larynx
* Participant should be able to swallow liquids or has an adequately functioning feeding tube, gastrostomy, or jejunostomy in place. For participants requiring liquid nutrition at baseline or during the study including the follow-up period, access to liquid nutrition supply should be ensured
* Participant with evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by CT scan and/or MRI, based on RECIST v 1.1.
* Adequate hematological, hepatic, and renal function as defined in the protocol
* Other protocol defined inclusion criteria could apply
Exclusion Criteria:
* Primary tumor of nasopharyngeal, paranasal sinuses, nasal, or oral cavity, salivary, thyroid, or parathyroid gland pathologies, skin, or unknown primary site
* Metastatic disease (Stage IVC as per AJCC/TNM, 8th Edition)
* Existing need of a hearing aid or greater than or equal to (\>=) 25 decibel shift over 2 contiguous frequencies on a pretreatment hearing test as clinically indicated
* Known history of infection with human immunodeficiency virus (HIV). If unknown history of HIV, an HIV screening test is to be performed and participants with positive serology for HIV-1/2 must be excluded
* Known gastrointestinal disorder with clinically established malabsorption syndrome and major gastrointestinal surgery in the last 12 months that may limit oral absorption
* Other protocol defined exclusion criteria could apply
Inclusion Criteria
Inclusion Criteria:
* Participants having an Eastern Cooperative Oncology Group Performance Score (ECOG PS) of 0 - 1
* Histologically confirmed diagnosis in previously untreated Locally Advanced Squamous Cell Carcinoma of Head and neck (LA SCCHN) patient (Stage III, IVA, or IVB according to the American Joint Committee on Cancer \[AJCC\]/ Tumor Nodes and metastases (TNM) Staging System, 8th Edition) suitable for definitive Chemoradiotherapy (CRT), with one of the following primary sites: oropharynx (OPC) Human Papillomavirus (HPV)-negative, hypopharynx, and larynx
* Participant should be able to swallow liquids or has an adequately functioning feeding tube, gastrostomy, or jejunostomy in place. For participants requiring liquid nutrition at baseline or during the study including the follow-up period, access to liquid nutrition supply should be ensured
* Participant with evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by CT scan and/or MRI, based on RECIST v 1.1.
* Adequate hematological, hepatic, and renal function as defined in the protocol
* Other protocol defined inclusion criteria could apply
* Participants having an Eastern Cooperative Oncology Group Performance Score (ECOG PS) of 0 - 1
* Histologically confirmed diagnosis in previously untreated Locally Advanced Squamous Cell Carcinoma of Head and neck (LA SCCHN) patient (Stage III, IVA, or IVB according to the American Joint Committee on Cancer \[AJCC\]/ Tumor Nodes and metastases (TNM) Staging System, 8th Edition) suitable for definitive Chemoradiotherapy (CRT), with one of the following primary sites: oropharynx (OPC) Human Papillomavirus (HPV)-negative, hypopharynx, and larynx
* Participant should be able to swallow liquids or has an adequately functioning feeding tube, gastrostomy, or jejunostomy in place. For participants requiring liquid nutrition at baseline or during the study including the follow-up period, access to liquid nutrition supply should be ensured
* Participant with evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by CT scan and/or MRI, based on RECIST v 1.1.
* Adequate hematological, hepatic, and renal function as defined in the protocol
* Other protocol defined inclusion criteria could apply
Gender
All
Gender Based
false
Keywords
Unresected
Combination with CRT
Stage III
Stage IVA
Stage IVB
Oropharynx
Hypopharynx
Larynx
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT06056310
Org Class
Industry
Org Full Name
EMD Serono
Org Study Id
MS202359_0025
Overall Status
Terminated
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Single Arm, Open Label, Phase 1b Study of Xevinapant in Combination With Weekly Cisplatin and Intensity-modulated Radiotherapy to Assess Safety and Tolerability in Participants With LA SCCHN, Suitable for Definitive Chemoradiotherapy (HyperlynX)
Primary Outcomes
Outcome Measure
Number of Participants with Dose limiting toxicity (DLT)-like events
Outcome Time Frame
From Day 1 up to 5 Weeks
Secondary Ids
Secondary Id
2023-505796-76-00
Secondary Outcomes
Outcome Time Frame
From Day 1 up to 18 weeks (Each cycle is of 3 Weeks)
Outcome Measure
Number of Participants with Adverse Events (AEs) and Treatment-Related AEs (TRAE)
Outcome Time Frame
From Screening up to Cycle 3 Day 4 (Day 67)
Outcome Measure
Absolute values and changes in estimated glomerular filtration rate (eGFR)
Outcome Time Frame
Time from first administration of study intervention until Progressive Disease (PD) or death, whichever is earlier assessed approximately up to 1.6 years
Outcome Measure
Objective Response (OR) According to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 criteria as assessed by Investigator
Outcome Time Frame
Time from first administration of study intervention until PD or death, whichever is earlier assessed approximately up to 1.6 years
Outcome Measure
Progression Free Survival (PFS) According to RECIST version 1.1 Criteria as Assessed by Investigator
Outcome Description
LRC is defined as the time from date of the first treatment until date of the first occurrence of progression at the site of the primary tumor or the locoregional lymph nodes.
Outcome Time Frame
From randomization to the earliest between PFS event (progression at the site of the primary tumor or the locoregional lymph nodes) or End of Study assessed approximately up to 1.6 years
Outcome Measure
Locoregional Control (LRC) According to RECIST version 1.1 Criteria As assessed by Investigator
Outcome Time Frame
From randomization to the earliest between PFS event (progression at the site of the primary tumor or the locoregional lymph nodes) or End of Study, assessed approximately up to 1.6 years
Outcome Measure
Time to Subsequent Systemic Cancer Treatments
See Also Links
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
Rafi Kabarriti
Investigator Email
RKABARRI@MONTEFIORE.ORG