A Randomized, Double-Blind, Adaptive, Phase II/III Study of GSK3359609 in Combination with Pembrolizumab and 5FU-Platinum Chemotherapy versus Placebo in Combination with Pembrolizumab plus 5FU-Platinum Chemotherapy for First-Line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma.
- Conditions
- Recurrent/Metastatic Head and Neck Squamous Cell CarcinomaMedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003981-42-IT
- Lead Sponsor
- GLAXOSMITHKLINE RESEARCH AND DEVELOPMENT
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 640
1. Capable of giving signed informed consent/assent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol
2. Male or female, age =>18 years; at the time consent is obtained
3. Histological or cytological documentation of 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 curatively intended systemic treatment)
6. Measurable disease per response evaluation criteria in solid tumors (RECIST) version 1.1
7. (ECOG) Performance Status (PS) score of 0 or 1
8. Adequate organ function as defined in Table 3 of the study protocol
9. Life expectancy of at least 12 weeks
10. Female participants: must not be pregnant (as confirmed by a negative serum beta-human chorionic gonadotrophin [ß-hCG] test in females of reproductive potential; for further details refer to Section 10.4 of the protocol), not breastfeeding, and at least one of the following conditions apply:
a) Not a woman of childbearing potential (WOCBP) as defined in Section 10.4.1. of the protocol
b) A WOCBP who agrees to use a highly effective method of birth control from 30 days prior to randomization and for at least 120 days after the last dose of study treatment. Refer to Section 10.4.2 for permitted contraceptive methods
c) The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy
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. Refer to Section 10.4.2 for permitted contraceptive methods; contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
12. Provide tumor tissue from excisional or core biopsy (fine needle aspirates and bone biopsies are not acceptable) acquired within 2 years prior to randomization for PD-L1 immunohistochemistry (IHC) testing by central laboratory. A fresh tumor biopsy, using a procedure that is safe for the participant on a lesion not previously irradiated (unless lesion progressed) will be required if previously acquired tumor tissue (i.e., archival tumor tissue) was acquired > 2 years or is unavailable//unsuitable for PD-L1 testing.
13. Have PD-L1 IHC CPS status by central laboratory testing (refer to Section 5.4 for definition of screen failure based on PD-L1 CPS restrictions); refer to Section8.8.3 for details on PD-L1 IHC assay. Participants in countries governed under the European Commission are required to have PD-L1 CPS = 1 status.
a) A specific PD-L1 CPS status may be required to fulfill eligibility (refer to Section 9.2 for details on estimated number of participants by PD-L1 CPS status) if a PD-L1 CPS status cap is implemented (study population proportion by PD-L1 CPS status will not exceed 5% of the planned proportions of the PD-L1 CPS subgroups (CPS =
1. Prior therapy with an anti-PD-1/L1/L2, anti-ICOS directed agent
2. Systemic approved or investigational anticancer therapy within 30 days or 5 halflives of the drug, whichever is shorter.
3. Has high risk of bleeding (to tumors encasing or infiltrating a major vessel, i.e., carotid, jugular, bronchial artery, and/or exhibits other high-risk features such as a fistula, significant cavitary lesions, prior history of hemorrhage [=60 days])
4. Active tumor bleeding
5. Grade 3 or Grade 4 hypercalcemia
6. Major surgery =28 days prior to randomization. Participants must have also fully
recovered from any surgery (major or minor) and/or its complications before randomization
7. Toxicity from previous anticancer treatment that includes:
a. Grade 3/Grade 4 toxicity considered related to prior immunotherapy and that led to treatment discontinuation.b. 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 (including platelets or red blood cells) or
administration of colony stimulating factors within 14 days prior to randomization
9. Central nervous system (CNS) metastases, (see protocol for further information)
10. Invasive malignancy or history of invasive malignancy other than disease under study within the last 3 years (see protocol for further information)
11. Autoimmune disease (current or history; refer to Table 19) 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 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 intraabdominal 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 which include:
a. Serious, uncontrolled cardiac arrhythmia or clinically significant electrocardiogram abnormalities including second degree (Type II) or third-degree atrioventricular block b. Cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting or
bypass grafting c. Congestive heart failure (Class II, III, or IV) as defined by the New York Heart Association functional classification system d. Symptomatic pericarditis
20. Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis
21. Active infection requiring systemic therapy
22. Known HIV infection, or positive test for hepatitis B or C
23. History of severe hypersensitivity to monoclonal antibodies or to the chemotherapies under investigation including any ingredient used in the
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method