| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma |
|
| 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 |
|
| 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 and 5FU-platinum chemotherapy compared with placebo in combination with pembrolizumab and platinum-based chemotherapy in the total (PD-L1 CPS all) population and in the PD-L1 positive (PD-L1 CPS ≥ 1) population. |
|
| E.2.2 | Secondary objectives of the trial |
Further compare the efficacy of GSK3359609 in combination with pembrolizumab and 5FU-platinum chemotherapy compared with placebo in combination with pembrolizumab and 5FU-platinum chemotherapy
Evaluate the safety and tolerability of GSK3359609 in combination with pembrolizumab and 5FU-platinum chemotherapy compared with placebo in combination with pembrolizumab and 5FU-platinum chemotherapy
Evaluate and compare disease and treatment related symptoms and impact on function and
HRQoL of GSK3359609 in combination with pembrolizumab and 5FU-platinum chemotherapy versus placebo in combination with pembrolizumab and 5FU-platinum chemotherapy |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
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 (minimum age requirement per local regulatory requirements)
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 guidelines
7. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1
8. Adequate organ function as defined in Table 3 of the study the 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 [β-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 (Note: duration of contraceptive use after last dose of chemotherapy must be consistent with local requirements; however, the minimum duration is 180 days after last dose of chemotherapy). 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.
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 (Note: duration of contraceptive use after last dose of chemotherapy must be consistent with local requirements; however, the minimum duration is 180 days after last dose of chemotherapy). 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 ≥ 20, 1≤ CPS <20 and CPS <1)
14. Have results from testing of HPV status for oropharyngeal cancer (refer to Section 8 and Table 1 for details on testing requirements)
A full list of inclusion criteria can be found in the study protocol Section 5.1 |
|
| E.4 | Principal exclusion criteria |
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. At least 14 days must have elapsed between the last dose of prior anticancer agent and the date of randomization
3. Has high risk of bleeding (examples include but are 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 a fistula, significant cavitary lesions, prior history of hemorrhage [≤60 days])
NOTE: following principal investigator consultation with the GSK Medical Monitor, certain cases may be approved by the GSK Medical Monitor upon review of the case (this review may include a requirement to provide images)
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 (including granulocyte colonystimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor, recombinant erythropoietin) 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
Note: Participants with carcinomatous meningitis or leptomeningeal spread are excluded regardless of clinical stability
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 cancer or successfully treated in situ carcinoma
c. Low-risk early stage prostate cancer defined as follows: Stage T1c or T2a
with a Gleason score ≤ 6 and prostatic-specific antigen (PSA) <10 ng/mL either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to randomization
11. Autoimmune disease (current or history; refer to Table 19) or syndrome that required systemic treatment within the past 2 years
Note: Replacement therapies which include physiological doses of corticosteroids for treatment of endocrinopathies (for example, adrenal insufficiency) are not considered systemic treatments.
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
Note:
a) Physiologic doses of corticosteroids for treatment of endocrinopathies or steroids with minimal systemic absorption, including topical, inhaled, or intranasal corticosteroids may be continued if the participant is on a stable dose
b) Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication) are permitted
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
Note: post-radiation changes in the lung related to prior radiotherapy and/or asymptomatic radiation-induced pneumonitis not requiring treatment (Grade 1) may be permitted if agreed upon by the investigator and Medical Monitor
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
For a full list of exclusion criteria please refer to the study protocol 5.2 Exclusion Criteria |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| OS in the total and the PD L1 CPS≥1 populations; PFS per RECIST v1.1 by Investigator assessment in the total population |
|
| 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 or death due to any cause per RECISTv1.1 guideline |
|
| E.5.2 | Secondary end point(s) |
| PFS (CPS ≥1 population), Milestone OS, Overall response rate, Disease control rate, and Duration of response per RECIST v1.1 by Investigator assessment in the CPS ≥1 and total population; safety and tolerability; time to deterioration in pain and physical function |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| PFS: date of randomization to date of progression per RECISTv1.1 guidelines; Milestone survival: 12, 24 and 36 months |
|
| 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 |
|
| 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 | 300 |
| 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 |
| Brazil |
| Canada |
| Chile |
| China |
| Hong Kong |
| Israel |
| Japan |
| Korea, Republic of |
| Mexico |
| Taiwan |
| United States |
| France |
| Poland |
| Sweden |
| Romania |
| Spain |
| Germany |
| Italy |
| Belgium |
| Denmark |
| Hungary |
| Ireland |
| Russian Federation |
| United Kingdom |
|
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| 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 | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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