Last updated: 04/18/2025 07:00:15
Study of GSK3359609 with pembrolizumab and 5-fluorouracil (5-FU)-platinum chemotherapy in participants with recurrent or metastatic Head and Neck Squamous Cell CarcinomaINDUCE-4
EudraCT ID
EU CT Number
Not applicable
Trial status
Other
Other
Trial overview
Official 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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Overall Survival (OS) in total population
Timeframe: Up to 32 months
OS in programmed death receptor-ligand 1 (PD-L1) combined positive score (CPS) >=1 population
Timeframe: Up to 32 months
Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 in total population
Timeframe: Up to 7.5 months
Secondary outcomes:
PFS per RECIST v1.1 in the PD-L1 CPS >=1 population
Timeframe: Up to 7.5 months
Milestone OS rate at 12, 24 and 36 months in total population
Timeframe: Months 12, 24 and 36
Milestone OS rate at 12, 24 and 36 months in PD-L1 CPS >=1 population
Timeframe: Months 12, 24 and 36
Overall Response Rate (ORR) per RECIST v1.1 in total population
Timeframe: Up to 7.5 months
ORR per RECIST v1.1 in PD-L1 CPS >=1 population
Timeframe: Up to 7.5 months
Disease Control Rate (DCR) per RECIST v1.1 in total population
Timeframe: Up to 7.5 months
DCR per RECIST v1.1 in PD-L1 CPS >=1 population
Timeframe: Up to 7.5 months
Duration of Response (DoR) per RECIST v1.1 in total population
Timeframe: Up to 7.5 months
DoR per RECIST v1.1 in PD-L1 CPS >=1 population
Timeframe: Up to 7.5 months
Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) in total population
Timeframe: Up to 10.5 months
Number of participants with adverse Events of Special Interest (AESI) in total population
Timeframe: Up to 10.5 months
Number of participants with AEs and SAEs in PD-L1 CPS>=1 population
Timeframe: Up to 10.5 months
Number of participants with AESIs in PD-L1 CPS>=1 population
Timeframe: Up to 10.5 months
Severity of AEs and SAEs in total population
Timeframe: Up to 10.5 months
Severity of AESIs in total population
Timeframe: Up to 10.5 months
Severity of AEs and SAEs in PD-L1 CPS>=1 population
Timeframe: Up to 10.5 months
Severity of AESI in PD-L1 CPS>=1 population
Timeframe: Up to 10.5 months
Number of participants with dose modifications in total population
Timeframe: Up to 7.5 months
Number of participants with dose modifications in PD-L1 CPS>=1 population
Timeframe: Up to 7.5 months
Time to deterioration in pain in total populations
Timeframe: Up to 7.5 months
Time to deterioration in pain in PD-L1 CPS >=1 populations
Timeframe: Up to 7.5 months
Time to deterioration in physical function in total population
Timeframe: Up to 7.5 months
Time to deterioration in physical function in PD-L1 CPS >=1 population
Timeframe: Up to 7.5 months
Interventions:
Enrollment:
118
Primary completion date:
2021-27-04
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Neoplasms, Head and Neck
Product
carboplatin
Collaborators
Merck Sharp & Dohme Corp.
Study date(s)
August 2020 to September 2023
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- Capable of giving signed informed consent
- Male or female, age >=18 years
- 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)
Inclusion and exclusion criteria
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.
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.
Trial location(s)
Study documents
Study report synopsis
Available language(s): English
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Other
Actual primary completion date
2021-27-04
Actual study completion date
2023-19-09
Plain language summaries
Summary of results in plain language
Available language(s): English, Danish, French, French (Belgium), French (Canadian), German, Italian, Korean, Polish, Portuguese (Brazil), Romanian, Russian, Spanish (Argentina), Spanish, Swedish, Japanese
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
Additional information
Not applicable
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