Metastatic or Recurrent Head and Neck Squamous-Cell Carcinoma with PD-L1 Expressing Tumors MedDRA version: 22.0 Level: LLT Classification code 10082179 Term: Squamous cell carcinoma of head and neck metastatic System Organ Class: 100000004864
Conditions
Sponsors
Nektar Therapeutics
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Provide written, informed consent to participate in the study and follow the study procedures. • Male or female patients, age 18 years or older on the day of signing the informed consent form. Have histologically or cytologically-confirmed recurrent or metastatic HNSCC that is considered incurable by local therapies. o No prior systemic therapy for recurrent or metastatic disease. Systemic therapy given as part of multimodal treatment for locally advanced disease is allowed if completed more than 6 months prior to signing consent. o The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx. o Patients may not have a primary tumor site of nasopharynx (any histology) and/or unknown primary. • Have measurable disease based on RECIST 1.1 as determined by the local site Investigator. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions since irradiation. • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. • Tumor tissue from a core, incisional, or excisional biopsy (fine needle aspirates are not acceptable) to the central laboratory for determination of PD-L1 status (if not determined at local laboratory) and exploratory biomarker analyses. A newly obtained biopsy is strongly preferred, but archival tumor biopsy may be used and provided (see Section 8.3.1). • The tumor must have positive PD-L1 expression (ie, CPS = 1) as determined with the PD-L1 IHC 22C3 PharmDx diagnostic kit at either a local or central laboratory. • Patients with oropharyngeal cancer: must have results from testing of HPV status defined as p16 IHC testing using CINtec® p16 Histology assay (Ventana Medical Systems Inc., Tucson AZ). If HPV status was previously tested using this method, no additional testing is required. Note: If local p16 testing results are not available, or cannot be assessed by the specified method, a tumor tissue sample may be submitted to the central laboratory for p16 testing. Patients with oral cavity, hypopharynx, or larynx cancers: HPV testing by p16 IHC is not required as by convention these tumor locations are assumed to be HPV negative. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 320 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 180
Exclusion criteria
Exclusion criteria: • Has disease that is suitable for local therapy administered with curative intent. • Has progressive disease within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC. • Has had radiation therapy (or other non-systemic therapy) within 2 weeks prior to initiation of study drug, or patient has not fully recovered (ie, = Grade 1 or at baseline) from AEs due to a previously administered treatment. A 1-week washout is permitted for palliative radiation (= 2 weeks of radiotherapy) to non-central nervous system (CNS) disease. Note: o Patients with = Grade 2 neuropathy or = Grade 2 alopecia are an exception to this criterion and qualify for the study. o If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. • Has a life expectancy of less than 3 months and/or has rapidly progressing disease (eg, tumor bleeding, uncontrolled tumor pain) as determined by Investigator. • Has a known additional malignancy that is progressing or has required active treatment within 5 years prior to the first dose of study drug with the exception of: curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, curatively resected in situ cervical cancer, and curatively resected in situ breast cancer. • Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. Corticosteroid use as pre-medication for allergic reactions (eg, intravenous [IV] contrast) is allowed. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To compare the overall survival (OS) of bempegaldesleukin plus pembrolizumab versus pembrolizumab monotherapy. 2. To compare the objective response rate (ORR) of bempegaldesleukin plus pembrolizumab;Secondary Objective: 1. To compare progression-free survival (PFS). 2. To compare time to deterioration in global health status/quality of life, pain, and swallowing. 3. To compare mean change from baseline in global health status/quality of life. 4. To compare the overall safety and tolerability.;Primary end point(s): The primary endpoints are: 1. OS, defined as the time from randomization to death due to any cause. 2. ORR, defined as the rate of confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR).;Timepoint(s) of evaluation of this end point: 1. OS: time between the date of randomization and the date of death due to any cause. 2. ORR will be tested at a statistical significance level of 0.001 at the second interim analysis. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. PFS, defined as the time from randomization to the first documented disease progression (per RECIST 1.1 by BICR) or death due to any cause, whichever occurs first. 2. Time from baseline to a = 10-point decrease from baseline with confirmation by the subsequent visit of a = 10-point deterioration from baseline in: • Global health status/quality of life assessment based on the global health status/quality of life scales of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30). • Pain based on the pain multi-item scales of EORTC QLQ head and neck cancer specific module (EORTC QLQ-H&N35). • Swallowing based on the swallowing multi-item scales of EORTC QLQ-H&N353. 3. Mean change from baseline in global health status/quality of life scales of EORTC QLQ-C30 4. Safety will be based on assessments of treatment-emergent adverse events (AEs) and serious AEs (SAEs).;Timepoint(s) of evaluation of this end point: 1. PFS: from randomization to the first documented disease progression (per RECIST 1.1 by BICR) or death due to any cause, whichever occurs first. 2. Completed by patients at baseline and throughout the study. 3. Mean change from baseline in global health status/quality of life scales of EORTC QLQ-C30: completed by patients at baseline and throughout the study. 4. Safety will be based on assessments of treatment-emergent adverse events (AEs) and serious AEs (SAEs): from the baseline and throughout the study. | — |
Countries
Australia, Austria, Belgium, Canada, China, Czechia, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Portugal, Russian Federation, Singapore, Spain, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactProject Manager
PPD
Outcome results
None listed