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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04428333




Registration number
NCT04428333
Ethics application status
Date submitted
9/06/2020
Date registered
11/06/2020

Titles & IDs
Public title
Study of GSK3359609 With Pembrolizumab and 5-fluorouracil (5-FU)-Platinum Chemotherapy in Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Scientific title
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
Secondary ID [1] 0 0
2019-003981-42
Secondary ID [2] 0 0
209227
Universal Trial Number (UTN)
Trial acronym
INDUCE-4
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms, Head and Neck 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Feladilimab
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Placebo
Treatment: Drugs - Platinum based chemotherapy
Treatment: Drugs - Fluorouracil (5FU)

Experimental: Feladilimab + Pembrolizumab + 5-FU-platinum chemotherapy -

Placebo comparator: Placebo + Pembrolizumab + 5-FU-platinum chemotherapy -


Treatment: Drugs: Feladilimab
Humanized anti-inducible T cell co-stimulatory receptor (ICOS) immunoglobulin G4 (IgG4) monoclonal antibody (mAb)

Treatment: Drugs: Pembrolizumab
Humanized anti- programmed cell death receptor1 (anti-PD-1) IgG4 mAb

Treatment: Drugs: Placebo
Sterile normal saline

Treatment: Drugs: Platinum based chemotherapy
Cisplatin/carboplatin

Treatment: Drugs: Fluorouracil (5FU)
5-fluorouracil
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS) in mITT Population
Timepoint [1] 0 0
Up to approximately 7 months
Primary outcome [2] 0 0
OS in Programmed Death Receptor-ligand 1 (PD-L1) Combined Positive Score (CPS) =1 Population
Timepoint [2] 0 0
Up to approximately 7 months
Primary outcome [3] 0 0
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 in mITT Population
Timepoint [3] 0 0
Up to approximately 7 months
Secondary outcome [1] 0 0
PFS Per RECIST v1.1 in the PD-L1 CPS =1 Population
Timepoint [1] 0 0
Up to approximately 7 months
Secondary outcome [2] 0 0
Milestone OS Rate at 12, 24 and 36 Months in mITT Population
Timepoint [2] 0 0
Months 12, 24 and 36
Secondary outcome [3] 0 0
Milestone OS Rate at 12, 24 and 36 Months in PD-L1 CPS =1 Population
Timepoint [3] 0 0
Months 12, 24 and 36
Secondary outcome [4] 0 0
Overall Response Rate (ORR) Per RECIST v1.1 in mITT Population
Timepoint [4] 0 0
Up to approximately 7 months
Secondary outcome [5] 0 0
ORR Per RECIST v1.1 in PD-L1 CPS =1 Population
Timepoint [5] 0 0
Up to approximately 7 months
Secondary outcome [6] 0 0
Disease Control Rate (DCR) Per RECIST v1.1 in mITT Population
Timepoint [6] 0 0
Up to approximately 7 months
Secondary outcome [7] 0 0
DCR Per RECIST v1.1 in PD-L1 CPS =1 Population
Timepoint [7] 0 0
Up to approximately 7 months
Secondary outcome [8] 0 0
Duration of Response (DoR) Per RECIST v1.1 in mITT Population
Timepoint [8] 0 0
Up to approximately 7 months
Secondary outcome [9] 0 0
DoR Per RECIST v1.1 in PD-L1 CPS =1 Population
Timepoint [9] 0 0
Up to approximately 7 months
Secondary outcome [10] 0 0
Number of Participants With Adverse Events (AEs) in Safety Population
Timepoint [10] 0 0
Up to approximately 7 months
Secondary outcome [11] 0 0
Number of Participants With Serious Adverse Events (SAEs) in Safety Population
Timepoint [11] 0 0
Up to approximately 7 months
Secondary outcome [12] 0 0
Number of Participants With Adverse Events of Special Interest (AESI) in Safety Population
Timepoint [12] 0 0
Up to approximately 7 months
Secondary outcome [13] 0 0
Number of Participants With AEs in PD-L1 CPS =1 Population
Timepoint [13] 0 0
Up to approximately 7 months
Secondary outcome [14] 0 0
Number of Participants With SAEs in PD-L1 CPS =1 Population
Timepoint [14] 0 0
Up to approximately 7 months
Secondary outcome [15] 0 0
Number of Participants With AESIs in PD-L1 CPS =1 Population
Timepoint [15] 0 0
Up to approximately 7 months
Secondary outcome [16] 0 0
Severity of AEs in Safety Population
Timepoint [16] 0 0
Up to approximately 7 months
Secondary outcome [17] 0 0
Severity of SAEs in Safety Population
Timepoint [17] 0 0
Up to approximately 7 months
Secondary outcome [18] 0 0
Severity of AESIs in Safety Population
Timepoint [18] 0 0
Up to approximately 7 months
Secondary outcome [19] 0 0
Severity of AEs in PD-L1 CPS =1 Population
Timepoint [19] 0 0
Up to approximately 7 months
Secondary outcome [20] 0 0
Severity of SAEs in PD-L1 CPS =1 Population
Timepoint [20] 0 0
Up to approximately 7 months
Secondary outcome [21] 0 0
Severity of AESI in PD-L1 CPS =1 Population
Timepoint [21] 0 0
Up to approximately 7 months
Secondary outcome [22] 0 0
Number of Participants With Dose Modifications in Safety Population
Timepoint [22] 0 0
Up to approximately 7 months
Secondary outcome [23] 0 0
Number of Participants With Dose Modifications in PD-L1 CPS =1 Population
Timepoint [23] 0 0
Up to approximately 7 months
Secondary outcome [24] 0 0
Time to Deterioration (TTD) in Pain in mITT Population
Timepoint [24] 0 0
Up to approximately 7 months
Secondary outcome [25] 0 0
TTD in Pain in PD-L1 CPS =1 Population
Timepoint [25] 0 0
Up to approximately 7 months
Secondary outcome [26] 0 0
TTD in Physical Function in mITT Population
Timepoint [26] 0 0
Up to approximately 7 months
Secondary outcome [27] 0 0
TTD in Physical Function in PD-L1 CPS =1 Population
Timepoint [27] 0 0
Up to approximately 7 months

Eligibility
Key inclusion criteria
* Capable of giving signed informed consent
* Male or female, age >=18 years
* HNSCC that was diagnosed as recurrent or metastatic and considered incurable by local therapies.
* Primary tumor location of the oral cavity, oropharynx, hypopharynx or larynx.
* 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).
* Measurable disease per RECIST version 1.1 guidelines
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.
* Adequate organ function.
* Life expectancy of at least 12 weeks.
* Female participants: must not be pregnant, not breastfeeding, and be either not a woman of childbearing potential (WOCBP); or be 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.
* 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 periods.
* 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.
* Have PD-L1 IHC CPS status by central laboratory testing.
* Have results from testing of human papilloma virus (HPV) status for oropharyngeal cancer.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior therapy with an anti-PD-1/L1/L2, anti-Inducible T Cell Co-Stimulatory Receptor (ICOS) directed agent.
* Systemic approved or investigational anticancer therapy within 30 days or 5 half lives 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. - 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)
* Active tumor bleeding - Grade 3 or Grade 4 hypercalcemia.
* Major surgery less than or equal to (<=) 28 days prior to randomization.
* Participants must have also fully recovered from any surgery (major or minor) and/or its complications before randomization
* Toxicity from previous anticancer treatment that includes: a. Grade 3/Grade 4 toxicity considered related to prior immunotherapy and that led to treatment discontinuation and 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).
* Received transfusion of blood products or administration of colony stimulating factors within 14 days prior to randomization.
* 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.
* Invasive malignancy or history of invasive malignancy other than disease under study within the last 3 years with the exception of: a. any other invasive malignancy for which the participant was definitively treated, has been disease-free for <=3 years. b. curatively treated non-melanoma skin cancer or successfully treated in situ carcinoma and/or. c. low-risk early stage prostate cancer defined as: Stage T1c or T2a with a Gleason score <=6 and prostatic-specific antigen less than (<)10 nanograms per milliliter (ng/mL) either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to randomization.
* Autoimmune disease or syndrome that required systemic treatment within the past 2 years.
* Has a diagnosis of immunodeficiency or is receiving systemic steroids (>10 milligram [mg] oral prednisone or equivalent) or other immunosuppressive agents within 7 days prior to randomization.
* Receipt of any live vaccine within 30 days prior randomization.
* Prior allogeneic/autologous bone marrow or solid organ transplantation.
* Has current pneumonitis or history of non-infectious pneumonitis that required steroids or other immunosuppressive agents.
* Recent history (within the past 6 months) of uncontrolled symptomatic ascites, pleural or pericardial effusions.
* Recent history (within the past 6 months) of gastrointestinal obstruction that required surgery, acute diverticulitis, inflammatory bowel disease, or intra-abdominal abscess.
* Recent history of allergen desensitization therapy within 4 weeks of randomization.
* 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.
* 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.
* Active infection requiring systemic therapy.
* Known human immunodeficiency virus (HIV) infection, or positive test for hepatitis B active infection (presence of hepatitis B surface antigen), or hepatitis C active infection.
* History of severe hypersensitivity to monoclonal antibodies or to the chemotherapies under investigation including any ingredient used in the formulation.
* Known history of active tuberculosis.
* Any serious (>=Grade 3) and/or unstable pre-existing medical condition (aside from malignancy).
* Any 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.
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the date of randomization.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/08/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/09/2023
Sample size
Target
Accrual to date
Final
118
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Blacktown
Recruitment hospital [2] 0 0
GSK Investigational Site - Woolloongabba
Recruitment hospital [3] 0 0
GSK Investigational Site - Heidelberg
Recruitment hospital [4] 0 0
GSK Investigational Site - Melbourne
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
Argentina
State/province [2] 0 0
Entre Ríos
Country [3] 0 0
Argentina
State/province [3] 0 0
Santa Fe
Country [4] 0 0
Argentina
State/province [4] 0 0
Tucumán
Country [5] 0 0
Argentina
State/province [5] 0 0
Ciudad Autonoma de Buenos Aires
Country [6] 0 0
Argentina
State/province [6] 0 0
Ciudad Autónoma de Buenos Aires
Country [7] 0 0
Belgium
State/province [7] 0 0
Bruxelles
Country [8] 0 0
Belgium
State/province [8] 0 0
Edegem
Country [9] 0 0
Brazil
State/province [9] 0 0
Espírito Santo
Country [10] 0 0
Brazil
State/province [10] 0 0
Paraná
Country [11] 0 0
Brazil
State/province [11] 0 0
São Paulo
Country [12] 0 0
Canada
State/province [12] 0 0
Alberta
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
Canada
State/province [14] 0 0
Quebec
Country [15] 0 0
Denmark
State/province [15] 0 0
Koebenhavn Oe
Country [16] 0 0
France
State/province [16] 0 0
Bordeaux
Country [17] 0 0
France
State/province [17] 0 0
Lyon cedex 08
Country [18] 0 0
France
State/province [18] 0 0
Paris
Country [19] 0 0
France
State/province [19] 0 0
Poitiers cedex
Country [20] 0 0
France
State/province [20] 0 0
Strasbourg
Country [21] 0 0
Germany
State/province [21] 0 0
Baden-Wuerttemberg
Country [22] 0 0
Germany
State/province [22] 0 0
Niedersachsen
Country [23] 0 0
Germany
State/province [23] 0 0
Sachsen
Country [24] 0 0
Germany
State/province [24] 0 0
Berlin
Country [25] 0 0
Hungary
State/province [25] 0 0
Nyíregyháza
Country [26] 0 0
Ireland
State/province [26] 0 0
Dublin
Country [27] 0 0
Italy
State/province [27] 0 0
Campania
Country [28] 0 0
Italy
State/province [28] 0 0
Lazio
Country [29] 0 0
Italy
State/province [29] 0 0
Liguria
Country [30] 0 0
Italy
State/province [30] 0 0
Lombardia
Country [31] 0 0
Italy
State/province [31] 0 0
Toscana
Country [32] 0 0
Japan
State/province [32] 0 0
Osaka
Country [33] 0 0
Japan
State/province [33] 0 0
Tokyo
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Daegu-si
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Gyeonggi-do
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Hwasun-gun, Jeollanam-do
Country [37] 0 0
Korea, Republic of
State/province [37] 0 0
Seoul
Country [38] 0 0
Poland
State/province [38] 0 0
Bydgoszcz
Country [39] 0 0
Poland
State/province [39] 0 0
Gdynia
Country [40] 0 0
Poland
State/province [40] 0 0
Gliwice
Country [41] 0 0
Poland
State/province [41] 0 0
Lublin
Country [42] 0 0
Poland
State/province [42] 0 0
Tomaszow Mazowiecki
Country [43] 0 0
Poland
State/province [43] 0 0
Warszawa
Country [44] 0 0
Romania
State/province [44] 0 0
Bucuresti
Country [45] 0 0
Romania
State/province [45] 0 0
Cluj Napoca
Country [46] 0 0
Romania
State/province [46] 0 0
Craiova
Country [47] 0 0
Romania
State/province [47] 0 0
Floresti
Country [48] 0 0
Romania
State/province [48] 0 0
Otopeni
Country [49] 0 0
Romania
State/province [49] 0 0
Suceava
Country [50] 0 0
Russian Federation
State/province [50] 0 0
Pushkin
Country [51] 0 0
Spain
State/province [51] 0 0
Barcelona
Country [52] 0 0
Spain
State/province [52] 0 0
Madrid
Country [53] 0 0
Spain
State/province [53] 0 0
Valencia
Country [54] 0 0
Sweden
State/province [54] 0 0
Stockholm
Country [55] 0 0
United Kingdom
State/province [55] 0 0
London
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Nottingham
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
IPD for this study will be made available via the Clinical Study Data Request site.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Available to whom?
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://clinicalstudydatarequest.com


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04428333