We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04428333
Ethics application status
Date submitted
9/06/2020
Date registered
11/06/2020
Date last updated
7/05/2021

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
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-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 total population - OS in the total population, defined as the time from the date of randomization until the date of death due to any cause.
Timepoint [1] 0 0
Up to 66 months
Primary outcome [2] 0 0
OS in programmed death receptor-ligand 1 (PD-L1) combined positive score (CPS) >=1 population - OS in the PD-L1 CPS >=1 population, defined as the time from the date of randomization until the date of death due to any cause
Timepoint [2] 0 0
Up to 66 months
Primary outcome [3] 0 0
Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 in total population - PFS per RECIST v1.1 in the total population, defined as the time from the date of randomization until the date of disease progression or death due to any cause, whichever occurs first.
Timepoint [3] 0 0
Up to 48 months
Secondary outcome [1] 0 0
PFS per RECIST v1.1 in the PD-L1 CPS >=1 population - PFS per RECIST v1.1 in the PD-L1 CPS >= 1, defined as the time from the date of randomization until the date of disease progression or death due to any cause, whichever comes first
Timepoint [1] 0 0
Up to 48 months
Secondary outcome [2] 0 0
Milestone OS rate at 12, 24 and 36 months in total population - Milestone OS rate at 12, 24, and 36 months will be evaluated from survival curves.
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 - Milestone OS rate at 12, 24, and 36 months will be evaluated from survival curves.
Timepoint [3] 0 0
Months 12, 24 and 36
Secondary outcome [4] 0 0
Overall Response Rate (ORR) per RECIST v1.1 in total population - ORR is defined as the proportion of the participants who have a complete response (CR) or partial response (PR) as the best overall response per RECIST v1.1.
Timepoint [4] 0 0
Up to 66 months
Secondary outcome [5] 0 0
ORR per RECIST v1.1 in PD-L1 CPS >=1 population - ORR is defined as the proportion of the participants who have a CR or PR as the best overall response per RECIST v1.1.
Timepoint [5] 0 0
Up to 66 months
Secondary outcome [6] 0 0
Disease Control Rate (DCR) per RECIST v1.1 in total population - DCR is defined as the percentage of participants with a best overall response of CR or PR at any time plus stable disease (SD) meeting the minimum time of 18 weeks per RECIST v1.1.
Timepoint [6] 0 0
Up to 66 months
Secondary outcome [7] 0 0
DCR per RECIST v1.1 in PD-L1 CPS >=1 population - DCR is defined as the percentage of participants with a best overall response of CR or PR at any time SD meeting the minimum time of 18 weeks per RECIST v1.1.
Timepoint [7] 0 0
Up to 66 months
Secondary outcome [8] 0 0
Duration of Response (DoR) per RECIST v1.1 in total population - DoR is defined as the time from first documented evidence of CR or PR until first documented disease progression per RECIST v1.1, whichever occurs first, among participants who demonstrated CR or PR as the best overall response per RECIST v1.1.
Timepoint [8] 0 0
Up to 66 months
Secondary outcome [9] 0 0
DoR per RECIST v1.1 in PD-L1 CPS >=1 population - DoR is defined as the time from first documented evidence of CR or PR until first documented disease progression per RECIST v1.1, whichever occurs first, among participants who demonstrated CR or PR as the best overall response per RECIST v1.1.
Timepoint [9] 0 0
Up to 66 months
Secondary outcome [10] 0 0
Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) in total population - Number of participants with any AEs and SAEs per International Council on Harmonization (ICH) definitions.
Timepoint [10] 0 0
Up to 66 months
Secondary outcome [11] 0 0
Number of participants with adverse Events of Special Interest (AESI) in total population - AESI are defined as events of potential immunologic etiology, including immune-related (ir) AEs
Timepoint [11] 0 0
Up to 66 months
Secondary outcome [12] 0 0
Number of participants with AEs and SAEs in PD-L1 CPS>=1 population - Number of participants with any AEs and SAEs per ICH definitions.
Timepoint [12] 0 0
Up to 66 months
Secondary outcome [13] 0 0
Number of participants with AESIs in PD-L1 CPS>=1 population - AESI are defined as events of potential immunologic etiology, including irAEs
Timepoint [13] 0 0
Up to 66 months
Secondary outcome [14] 0 0
Severity of AEs and SAEs in total population - Severity for each AE and SAE will be reported during the study and will assign a grade according to the National Cancer Institute - Common Toxicity Criteria for Adverse Events (NCI-CTCAE) v5.0
Timepoint [14] 0 0
Up to 66 months
Secondary outcome [15] 0 0
Severity of AESIs in total population - Severity for each AESIs will be reported during the study and will assign a grade according to the NCI-CTCAE v5.0
Timepoint [15] 0 0
Up to 66 months
Secondary outcome [16] 0 0
Severity of AEs and SAEs in PD-L1 CPS>=1 population - Severity for each AE and SAE will be reported during the study and will assign a grade according to the NCI-CTCAE v5.0
Timepoint [16] 0 0
Up to 66 months
Secondary outcome [17] 0 0
Severity of AESI in PD-L1 CPS>=1 population - Severity for each AESI will be reported during the study and will assign a grade according to the NCI-CTCAE v5.0
Timepoint [17] 0 0
Up to 66 months
Secondary outcome [18] 0 0
Number of participants with dose modifications in total population - Number of participants with dose modifications (i.e. interruptions, discontinuations) in the total populations will be reported
Timepoint [18] 0 0
Up to 66 months
Secondary outcome [19] 0 0
Number of participants with dose modifications in PD-L1 CPS>=1 population - Number of participants with dose modifications (i.e. interruptions, discontinuations) in the PD-L1 CPS>=1 population will be reported.
Timepoint [19] 0 0
Up to 66 months
Secondary outcome [20] 0 0
Time to deterioration in pain in total populations - Time to deterioration in pain is defined as the time from the date of randomization to the date of first definitive meaningful deterioration in score measured by structured participants questionnaire.
Timepoint [20] 0 0
Up to 66 months
Secondary outcome [21] 0 0
Time to deterioration in pain in PD-L1 CPS >=1 populations - Time to deterioration in pain is defined as the time from the date of randomization to the date of first definitive meaningful deterioration in score measured by structured participants questionnaire.
Timepoint [21] 0 0
Up to 66 months
Secondary outcome [22] 0 0
Time to deterioration in physical function in total population - The time to deterioration in physical function will be measured by the participant-reported outcomes measurement.
Timepoint [22] 0 0
Up to 66 months
Secondary outcome [23] 0 0
Time to deterioration in physical function in PD-L1 CPS >=1 population - The time to deterioration in physical function will be measured by the participant-reported outcomes measurement.
Timepoint [23] 0 0
Up to 66 months

Eligibility
Key inclusion criteria
- Histological or cytological documentation of 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.

- 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
Gender
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.

- Has high risk of bleeding.

- Active tumor bleeding

- Grade 3 or Grade 4 hypercalcemia.

- Major surgery <=28 days prior to randomization.

- Toxicity from previous anticancer treatment that includes: a. Grade 3/Grade 4 toxicity
related to prior immunotherapy and that led to treatment discontinuation and 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 any other invasive malignancy for which
the participant was definitively treated, has been disease-free for <=3 years,
curatively treated non-melanoma skin cancer or successfully treated in situ carcinoma
and/or low-risk early stage prostate cancer.

- 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.

- 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 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 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
Argentina
State/province [5] 0 0
Entre Ríos
Country [6] 0 0
Argentina
State/province [6] 0 0
Santa Fe
Country [7] 0 0
Argentina
State/province [7] 0 0
Tucumán
Country [8] 0 0
Argentina
State/province [8] 0 0
Ciudad Autonoma de Buenos Aires
Country [9] 0 0
Argentina
State/province [9] 0 0
Ciudad Autónoma de Buenos Aires
Country [10] 0 0
Belgium
State/province [10] 0 0
Bruxelles
Country [11] 0 0
Belgium
State/province [11] 0 0
Edegem
Country [12] 0 0
Belgium
State/province [12] 0 0
Leuven
Country [13] 0 0
Brazil
State/province [13] 0 0
Espírito Santo
Country [14] 0 0
Brazil
State/province [14] 0 0
Paraná
Country [15] 0 0
Brazil
State/province [15] 0 0
São Paulo
Country [16] 0 0
Brazil
State/province [16] 0 0
Rio de Janeiro
Country [17] 0 0
Canada
State/province [17] 0 0
Alberta
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
China
State/province [20] 0 0
Guizhou
Country [21] 0 0
China
State/province [21] 0 0
Hubei
Country [22] 0 0
China
State/province [22] 0 0
Sichuan
Country [23] 0 0
Denmark
State/province [23] 0 0
Herlev
Country [24] 0 0
Denmark
State/province [24] 0 0
Koebenhavn Oe
Country [25] 0 0
Denmark
State/province [25] 0 0
Odense
Country [26] 0 0
France
State/province [26] 0 0
Avignon Cedex 9
Country [27] 0 0
France
State/province [27] 0 0
Bordeaux
Country [28] 0 0
France
State/province [28] 0 0
Lille
Country [29] 0 0
France
State/province [29] 0 0
Lyon cedex 08
Country [30] 0 0
France
State/province [30] 0 0
Paris
Country [31] 0 0
France
State/province [31] 0 0
Poitiers cedex
Country [32] 0 0
France
State/province [32] 0 0
Strasbourg
Country [33] 0 0
Germany
State/province [33] 0 0
Baden-Wuerttemberg
Country [34] 0 0
Germany
State/province [34] 0 0
Hessen
Country [35] 0 0
Germany
State/province [35] 0 0
Niedersachsen
Country [36] 0 0
Germany
State/province [36] 0 0
Nordrhein-Westfalen
Country [37] 0 0
Germany
State/province [37] 0 0
Sachsen
Country [38] 0 0
Germany
State/province [38] 0 0
Berlin
Country [39] 0 0
Ireland
State/province [39] 0 0
Dublin
Country [40] 0 0
Italy
State/province [40] 0 0
Campania
Country [41] 0 0
Italy
State/province [41] 0 0
Emilia-Romagna
Country [42] 0 0
Italy
State/province [42] 0 0
Lazio
Country [43] 0 0
Italy
State/province [43] 0 0
Liguria
Country [44] 0 0
Italy
State/province [44] 0 0
Lombardia
Country [45] 0 0
Italy
State/province [45] 0 0
Sicilia
Country [46] 0 0
Italy
State/province [46] 0 0
Toscana
Country [47] 0 0
Italy
State/province [47] 0 0
Veneto
Country [48] 0 0
Japan
State/province [48] 0 0
Chiba
Country [49] 0 0
Japan
State/province [49] 0 0
Fukuoka
Country [50] 0 0
Japan
State/province [50] 0 0
Hokkaido
Country [51] 0 0
Japan
State/province [51] 0 0
Hyogo
Country [52] 0 0
Japan
State/province [52] 0 0
Kagawa
Country [53] 0 0
Japan
State/province [53] 0 0
Osaka
Country [54] 0 0
Japan
State/province [54] 0 0
Shizuoka
Country [55] 0 0
Japan
State/province [55] 0 0
Tokyo
Country [56] 0 0
Korea, Republic of
State/province [56] 0 0
Daegu-si
Country [57] 0 0
Korea, Republic of
State/province [57] 0 0
Gyeonggi-do
Country [58] 0 0
Korea, Republic of
State/province [58] 0 0
Hwasun-gun, Jeollanam-do
Country [59] 0 0
Korea, Republic of
State/province [59] 0 0
Incheon
Country [60] 0 0
Korea, Republic of
State/province [60] 0 0
Seoul
Country [61] 0 0
Poland
State/province [61] 0 0
Bydgoszcz
Country [62] 0 0
Poland
State/province [62] 0 0
Gdynia
Country [63] 0 0
Poland
State/province [63] 0 0
Gliwice
Country [64] 0 0
Poland
State/province [64] 0 0
Katowice
Country [65] 0 0
Poland
State/province [65] 0 0
Lublin
Country [66] 0 0
Poland
State/province [66] 0 0
Tomaszow Mazowiecki
Country [67] 0 0
Poland
State/province [67] 0 0
Warszawa
Country [68] 0 0
Romania
State/province [68] 0 0
Bucuresti
Country [69] 0 0
Romania
State/province [69] 0 0
Cluj Napoca
Country [70] 0 0
Romania
State/province [70] 0 0
Craiova
Country [71] 0 0
Romania
State/province [71] 0 0
Floresti
Country [72] 0 0
Romania
State/province [72] 0 0
Iasi
Country [73] 0 0
Romania
State/province [73] 0 0
Otopeni
Country [74] 0 0
Romania
State/province [74] 0 0
Suceava
Country [75] 0 0
Romania
State/province [75] 0 0
Targu Mures
Country [76] 0 0
Russian Federation
State/province [76] 0 0
Poselok Kuzmolovsky
Country [77] 0 0
Russian Federation
State/province [77] 0 0
Pushkin
Country [78] 0 0
Spain
State/province [78] 0 0
Barcelona
Country [79] 0 0
Spain
State/province [79] 0 0
La Laguna-Tenerife
Country [80] 0 0
Spain
State/province [80] 0 0
Madrid
Country [81] 0 0
Spain
State/province [81] 0 0
Sevilla
Country [82] 0 0
Spain
State/province [82] 0 0
Valencia
Country [83] 0 0
Sweden
State/province [83] 0 0
Linköping
Country [84] 0 0
Sweden
State/province [84] 0 0
Stockholm
Country [85] 0 0
Taiwan
State/province [85] 0 0
Taipei
Country [86] 0 0
United Kingdom
State/province [86] 0 0
Lancashire
Country [87] 0 0
United Kingdom
State/province [87] 0 0
London
Country [88] 0 0
United Kingdom
State/province [88] 0 0
Nottingham
Country [89] 0 0
United Kingdom
State/province [89] 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 Corp.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate if the addition of GSK3359609 to pembrolizumab in
combination with 5FU-platinum based chemotherapy improves the efficacy of the pembrolizumab
combination with 5FU-platinum based chemotherapy in participants with recurrent or metastatic
(R/M) head and neck squamous cell carcinoma (HNSCC). This randomized, double-blinded, Phase
II/III study will compare the combination of GSK3359609 with pembrolizumab and 5FU-platinum
chemotherapy to placebo in combination with pembrolizumab and 5FU-platinum chemotherapy in
participants with recurrent or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx
or larynx. Approximately 640 participants will be enrolled in the study.
Trial website
https://clinicaltrials.gov/show/NCT04428333
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
US GSK Clinical Trials Call Center
Address 0 0
Country 0 0
Phone 0 0
877-379-3718
Fax 0 0
Email 0 0
GSKClinicalSupportHD@gsk.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04428333