E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma |
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E.1.1.1 | Medical condition in easily understood language |
Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065147 |
E.1.2 | Term | Malignant solid tumor |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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
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E.2.2 | Secondary objectives of the trial |
-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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 (except for systemic therapy given as part of multimodal treatment for locally advanced disease)
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 randomization for 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
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E.4 | Principal 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.Major surgery ≤28 days prior to randomization.
4. 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)
5. Received transfusion of blood products or administration of colony stimulating factors within 14 days prior to randomization
6. 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
7.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
8. Autoimmune disease (current or history) or syndrome that required systemic treatment within the past 2 years
9. 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
10. Receipt of any live vaccine within 30 days prior randomization
11. Prior allogeneic/autologous bone marrow or solid organ transplantation
12. Has current pneumonitis or history of non-infectious pneumonitis that required steroids or other immunosuppressive agents
13. Recent history (within the past 6 months) of uncontrolled symptomatic ascites, pleural or pericardial effusions
14. Recent history (within the past 6 months) of gastrointestinal obstruction that required surgery, acute diverticulitis, inflammatory bowel disease, or intra-abdominal abscess
15. Recent history of allergen desensitization therapy within 4 weeks of randomization
16. History or evidence of cardiac abnormalities within the 6 months prior to randomization
17. 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.
18. Active infection requiring systemic therapy
19.Known HIV infection, or positive test for hepatitis B active infection (presence of hepatitis B surface antigen), or hepatitis C active infection
20. History of severe hypersensitivity to monoclonal antibodies or any ingredient used in the study treatment formulations
21. Known history of active tuberculosis
22. Any serious and/or unstable pre-existing medical (aside from malignancy), psychiatric disorder, or other condition that could interfere with participant's safety, obtaining informed consent, or compliance to the study procedures in the opinion of the investigator
23. Is currently participating in (unless in follow-up phase and 4 weeks have elapsed from last dose of prior investigational agent), or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to date of randomization
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E.5 End points |
E.5.1 | 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
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E.5.1.1 | 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 |
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E.5.2 | 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
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E.5.2.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity and Patient Reported Outcomes |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 129 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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 |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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A participant is considered to have completed the study if he/she has completed all phases of the study including follow-up for survival or until follow-up for survival is no longer required (refer to Section 7.1).
The end of the study is defined as the date of the last visit of the last participant in the study.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |