Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma MedDRA version: 21.1 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 100000004864
Conditions
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study if all of the following criteria apply: 1. Capable of giving signed informed consent 2. Male or female, age =18 years at the time consent is obtained (minimum age requirement per local regulatory requirements) 3. Histological or cytological documentation of Head and Neck Squamous Cell Carcinoma (HNSCC) that was diagnosed as recurrent or metastatic and considered incurable by local therapies 4. Primary tumor location of the oral cavity, oropharynx, hypopharynx or larynx. 5. No prior systemic therapy administered in the recurrent or metastatic setting (with the exception of systemic therapy completed >6 months prior if given as part of multimodal treatment for locally advanced disease, and no disease progression/recurrence within 6 months of the completion of systemic treatment with curative intent). 6. Measurable disease per RECIST version 1.1 guidelines 7. ECOG Performance PS score of 0 or 1 8. Adequate organ function 9. Life expectancy of at least 12 weeks 10. Female participants: must not be pregnant, not breastfeeding, and at least one of the following conditions apply: a. Not a woman of childbearing potential (WOCBP) b. A WOCBP who agrees to use a method of birth control from 30 days prior to randomization and for at least 120 days after the last dose of study treatment. 11. Male participants with female partners of child-bearing potential: must agree to use a highly effective contraception while receiving study treatment and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period. 12. Provide tumor tissue from excisional or core biopsy (fine needle aspirates and bone biopsies are not acceptable) acquired within 2 years prior to date of PD-L1 immunohistochemistry (IHC) testing by central laboratory. 13. Have PD-L1 IHC CPS =1 status by central laboratory testing 14. Have results from testing of HPV status for oropharyngeal cancer 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 384 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 216
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: 1. Prior therapy with an anti-PD-1/L1/L2 and/or anti-ICOS directed agent 2. Systemic approved or investigational anticancer therapy within 30 days or 5 half-lives of the drug, whichever is shorter. 3. Has high risk of bleeding (examples include but not limited to tumors encasing or infiltrating a major vessel [i.e. carotid, jugular, bronchial artery) and/or exhibits other high-risk features such as an arteriovenous fistula) NOTE: Principal investigator should consult the GSK Medical Monitors to confirm eligibility of patients with disease features that may confer a high risk of tumor associated hemorrhage. 4. Active tumor bleeding 5. Grade 3 or Grade 4 hypercalcemia 6.Major surgery =28 days prior to randomization. 7. Toxicity from previous anticancer treatment that includes toxicity related to prior treatment that has not resolved to = Grade 1 (except alopecia, hearing loss, endocrinopathy managed with replacement therapy, and peripheral neuropathy which must be = Grade 2) 8. Received transfusion of blood products or administration of colony stimulating factors within 14 days prior to randomization 9. Central nervous system (CNS) metastases, with the following exception: Participants with asymptomatic CNS metastases who are clinically stable and have no requirement for steroids for at least 14 days prior to randomization 10. Invasive malignancy or history of invasive malignancy other than disease under study within the last 3 years, except as noted below: a.Any other invasive malignancy for which the participant was definitively treated, has been disease-free for =3 years and in the opinion of the principal investigator and GSK Medical Monitor will not affect the evaluation of the effects of the study treatment on the currently targeted malignancy, may be included in this clinical study b.Curatively treated non-melanoma skin or successfully treated in situ carcinoma c.Low-risk early stage prostate cancer 11. Autoimmune disease (current or history) or syndrome that required systemic treatment within the past 2 years 12. Has a diagnosis of immunodeficiency or is receiving systemic steroids (=10 mg oral prednisone per day or equivalent) or other immunosuppressive agents within 7 days prior to randomization 13. Receipt of any live vaccine within 30 days prior randomization 14. Prior allogeneic/autologous bone marrow or solid organ transplantation 15. Has current pneumonitis or history of non-infectious pneumonitis that required steroids or other immunosuppressive agents 16. Recent history (within the past 6 months) of uncontrolled symptomatic ascites, pleural or pericardial effusions 17. Recent history (within the past 6 months) of gastrointestinal obstruction that required surgery, acute diverticulitis, inflammatory bowel disease, or intra-abdominal abscess 18. Recent history of allergen desensitization therapy within 4 weeks of randomization 19. History or evidence of cardiac abnormalities within the 6 months prior to randomization 20. Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice. 21. Active infection requiring systemic therapy 22. Known HIV infection, or positive test for hepatitis B active infection (presence of hepatitis B surface antigen), or hepatitis C activ
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Compare the efficacy of GSK3359609 in combination with pembrolizumab to pembrolizumab plus placebo in the Programmed Death Ligand 1 (PD L1) expression positive (CPS = 1) population and in the PD-L1 expression high (CPS =20) population ;Secondary Objective: -Further compare the efficacy of GSK3359609 in combination with pembrolizumab compared with pembrolizumab plus placebo -Evaluate the safety and tolerability of GSK3359609 in combination with pembrolizumab compared with pembrolizumab plus placebo -Evaluate and compare disease related symptoms and impact on function and health-related quality of life (HRQoL) of GSK3359609/pembrolizumab versus pembrolizumab plus placebo;Primary end point(s): •OS, defined as the time from the date of randomization to the date of death due to any cause •PFS per RECIST v1.1 by investigator assessment, defined as the time from the date of randomization to the date of first documented disease progression or death due to any cause, whichever comes first ;Timepoint(s) of evaluation of this end point: OS: date of randomization to date of death, PFS: date of randomization to date of disease progression per RECISTv1.1 guideline | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •PFS per iRECIST (iPFS) by investigator assessment in the PD-L1 CPS =1 population •PFS per RECIST v1.1 and iPFS by investigator assessment in PD-L1 CPS =20 population •Milestone OS rate at 12 and 24 months in the PD-L1 CPS =1 and CPS =20 populations •ORR per RECIST v1.1 by investigator assessment in the PD-L1 CPS =1 and CPS =20 populations •DCR per RECIST v1.1 by investigator assessment in the PD-L1 CPS =1 and CPS =20 populations •DoR per RECIST v1.1 by investigator assessment in the PD-L1 CPS =1 and CPS =20 populations •Frequency and severity of AEs, AESI, SAEs •Dose modifications (i.e., interruptions, discontinuations) •The time to deterioration in pain measured by the EORTC QLQ-H&N35 pain domain in the PD-L1 CPS =1 and CPS =20 populations •The time to deterioration in physical function measured by the PROMIS PF 8c in the PD-L1 CPS =1 and CPS =20 populations ;Timepoint(s) of evaluation of this end point: PFS: date of randomization to date of progression per immune-based PFS; Milestone survival: 12 and 24 months | — |
Countries
Argentina, Australia, Austria, Brazil, Canada, China, Colombia, Denmark, France, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Norway, Poland, Portugal, Romania, Russian Federation, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactGSK Clinical Support Help Desk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed