Neoplasms, Head and NeckPhase 3INDUCE-4NCT04428333
Study of GSK3359609 With Pembrolizumab and 5-fluorouracil (5-FU)-Platinum Chemotherapy in Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
A Phase 3 study testing Feladilimab, Pembrolizumab and Platinum based chemotherapy in people with Neoplasms, Head and Neck, run by GlaxoSmithKline at 71 sites in 19 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms, Head and Neck
- What is being tested?
- Feladilimab, Pembrolizumab and Platinum based chemotherapy
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 117 participants
- Where
- 71 sitesin 19 countries
- Study dates
- 12 Aug 2020to 19 Sep 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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).
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- 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 locations and contacts
71 sites in 19 countries.
71 sites in 19 countries
Canada6 sites
GSK Investigational Site
Edmonton, Alberta, T6G 1Z2
GSK Investigational Site
Hamilton, Ontario, L8V 5C2
GSK Investigational Site
London, Ontario, N6A 4G5
GSK Investigational Site
Montreal, Quebec, H2X 3E4
GSK Investigational Site
Toronto, Ontario, M4N 3M5
GSK Investigational Site
Toronto, Ontario, M5G 2M9
Italy6 sites
GSK Investigational Site
Brescia, 25123
GSK Investigational Site
Florence, 59100
GSK Investigational Site
Milan, 20132
GSK Investigational Site
Naples, 80131
GSK Investigational Site
Roma, 00144
GSK Investigational Site
Savona, 17100
Poland6 sites
GSK Investigational Site
Bydgoszcz, 85-796
GSK Investigational Site
Gdynia, 81-519
GSK Investigational Site
Gliwice, 44-102
GSK Investigational Site
Lublin, 20-090
GSK Investigational Site
Tomaszów Mazowiecki, 97-200
GSK Investigational Site
Warsaw, 02-781
Romania6 sites
GSK Investigational Site
Bucharest, 021389
GSK Investigational Site
Cluj-Napoca, 400015
GSK Investigational Site
Craiova, 200347
GSK Investigational Site
Floreşti, 407280
GSK Investigational Site
Otopeni, 075100
GSK Investigational Site
Suceava, 720284
South Korea6 sites
GSK Investigational Site
Daegu, 42601
GSK Investigational Site
Gyeonggi-do, 10408
GSK Investigational Site
Hwasun, 58128
GSK Investigational Site
Incheon, 21565
GSK Investigational Site
Seoul, 05505
GSK Investigational Site
Seoul, 137-701
Spain6 sites
GSK Investigational Site
Barcelona, 08035
GSK Investigational Site
Madrid, 28040
GSK Investigational Site
Madrid, 28041
GSK Investigational Site
Madrid, 28046
GSK Investigational Site
Madrid, 28050
GSK Investigational Site
Valencia, 46026
Argentina5 sites
GSK Investigational Site
Buenos Aires, 1012
GSK Investigational Site
Buenos Aires, C1426ABP
GSK Investigational Site
Oro Verde Entre RIos, E3100XAD
GSK Investigational Site
Rosario, S2000DBS
GSK Investigational Site
San Miguel de Tucumán, T4000
France5 sites
GSK Investigational Site
Bordeaux, 33000
GSK Investigational Site
Lyon, 69373
GSK Investigational Site
Paris, 75005
GSK Investigational Site
Poitiers, 86021
GSK Investigational Site
Strasbourg, 67200
Australia4 sites
GSK Investigational Site
Blacktown, 2148
GSK Investigational Site
Heidelberg, 3084
GSK Investigational Site
Melbourne, 3000
GSK Investigational Site
Woolangabba, 4102
Germany4 sites
GSK Investigational Site
Berlin, 12203
GSK Investigational Site
Hanover, 30625
GSK Investigational Site
Leipzig, 04103
GSK Investigational Site
Ulm, 89075
Japan4 sites
GSK Investigational Site
Osaka, 541-8567
GSK Investigational Site
Osaka, 589-8511
GSK Investigational Site
Tokyo, 104-0045
GSK Investigational Site
Tokyo, 135-8550
Brazil3 sites
GSK Investigational Site
Curitiba, 81520-060
GSK Investigational Site
São Paulo, 01246-000
GSK Investigational Site
Vitória, 29043-260
United Kingdom3 sites
GSK Investigational Site
London, SW3 6JJ
GSK Investigational Site
Nottingham, NG5 1PB
GSK Investigational Site
Sutton, SM2 5PT
Belgium2 sites
GSK Investigational Site
Brussels, 1070
GSK Investigational Site
Edegem, 2650
About this study
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
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.
- Conditions
- Neoplasms, Head and Neck
- Being tested
- Feladilimab, Pembrolizumab, Placebo, Platinum based chemotherapy, Fluorouracil (5FU)
- Keywords
- GSK3359609, Pembrolizumab, Programmed cell death receptor 1, Inducible T cell co-stimulatory receptor, Keynote-A02, Phase II/III, Platinum-based chemotherapy, 5FU, Head and neck squamous cell carcinoma
- Medical subject headings
- Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FeladilimabDrug
Humanized anti-inducible T cell co-stimulatory receptor (ICOS) immunoglobulin G4 (IgG4) monoclonal antibody (mAb)
PembrolizumabDrug
Humanized anti- programmed cell death receptor1 (anti-PD-1) IgG4 mAb
PlaceboDrug
Sterile normal saline
Platinum based chemotherapyDrug
Cisplatin/carboplatin
Fluorouracil (5FU)Drug
5-fluorouracil
| Study group | Role | What they receive |
|---|---|---|
| Feladilimab + Pembrolizumab + 5-FU-platinum chemotherapy | Experimental | Not described Receives: Drug: Feladilimab; Drug: Pembrolizumab; Drug: Platinum based chemotherapy; Drug: Fluorouracil (5FU) |
| Placebo + Pembrolizumab + 5-FU-platinum chemotherapy | Placebo comparator | Not described Receives: Drug: Pembrolizumab; Drug: Placebo; Drug: Platinum based chemotherapy; Drug: Fluorouracil (5FU) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS) in mITT Population
OS was defined as the time from the date of randomization to the date of death due to any cause. Kaplan-Meier estimate for the median OS is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.
Measured: Up to approximately 7 months
OS in Programmed Death Receptor-ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Population
OS was defined as the time from the date of randomization until the date of death due to any cause. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells. Kaplan-Meier estimate for the median OS is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.
Measured: Up to approximately 7 months
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 in mITT Population
PFS per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 was defined as the time from the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first. Kaplan-Meier estimate for the median PFS is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.
Measured: Up to approximately 7 months
Secondary outcomes (27)
PFS Per RECIST v1.1 in the PD-L1 CPS ≥1 Population
PFS per RECIST v1.1 was defined as the time from the date of randomization until the date of disease progression or death due to any cause, whichever occurs first. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells. Kaplan-Meier estimate for the median PFS is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.
Measured: Up to approximately 7 months
Milestone OS Rate at 12, 24 and 36 Months in mITT Population
Milestone OS rate at 12, 24, and 36 months was not evaluated.
Measured: Months 12, 24 and 36
Milestone OS Rate at 12, 24 and 36 Months in PD-L1 CPS ≥1 Population
Milestone OS rate at 12, 24, and 36 months was not evaluated. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells.
Measured: Months 12, 24 and 36
Overall Response Rate (ORR) Per RECIST v1.1 in mITT Population
ORR per RECIST v1.1 was 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 based upon investigator assessment. As a randomized double-blind study in which primary endpoints are OS and PFS, the confirmation of CR and PR was not required. Rate and associated 2-sided 95 percent Exact (Clopper-Pearson) Confidence Intervals are provided for each treatment arm which are unadjusted.
Measured: Up to approximately 7 months
ORR Per RECIST v1.1 in PD-L1 CPS ≥1 Population
ORR per RECIST v1.1 was 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 based upon investigator assessment. As a randomized double-blind study in which primary endpoints are OS and PFS, the confirmation of CR and PR was not required. Rate and associated 2-sided 95 percent Exact (Clopper-Pearson) Confidence Intervals are provided for each treatment arm which are unadjusted. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells.
Measured: Up to approximately 7 months
Disease Control Rate (DCR) Per RECIST v1.1 in mITT Population
DCR per RECIST v1.1 based upon investigator assessment, was 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 15 weeks. A status of SD≥15 weeks will be assigned if the follow-up disease assessment has met the SD criteria at least once after the date of randomization at a minimum of 14 weeks (98 days) considering a one-week visit window. Rate and associated 2-sided 95 percent Exact (Clopper-Pearson) Confidence Intervals are provided for each treatment arm which are unadjusted.
Measured: Up to approximately 7 months
DCR Per RECIST v1.1 in PD-L1 CPS ≥1 Population
DCR per RECIST v1.1 based upon investigator assessment, was 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 15 weeks. A status of SD≥15 weeks will be assigned if the follow-up disease assessment has met the SD criteria at least once after the date of randomization at a minimum of 14 weeks (98 days) considering a one-week visit window. Rate and associated 2-sided 95 percent Exact (Clopper-Pearson) Confidence Intervals are provided for each treatment arm which are unadjusted. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells.
Measured: Up to approximately 7 months
Duration of Response (DoR) Per RECIST v1.1 in mITT Population
DoR per RECIST v1.1 is defined as the time from first documented evidence of CR or PR until first documented disease progression per RECIST v1.1 based upon investigator assessment or death due to any cause, whichever occurs first, among participants who demonstrated CR or PR as the best overall response per RECIST v1.1. Kaplan-Meier estimate for the median DoR is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.
Measured: Up to approximately 7 months
DoR Per RECIST v1.1 in PD-L1 CPS ≥1 Population
DoR per RECIST v1.1 is defined as the time from first documented evidence of CR or PR until first documented disease progression per RECIST v1.1 based upon investigator assessment or death due to any cause, whichever occurs first, among participants who demonstrated CR or PR as the best overall response per RECIST v1.1. Kaplan-Meier estimate for the median DoR is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells.
Measured: Up to approximately 7 months
Number of Participants With Adverse Events (AEs) in Safety Population
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention
Measured: Up to approximately 37.2 months
Number of Participants With Serious Adverse Events (SAEs) in Safety Population
SAE was defined as any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and other situations according to medical or scientific judgement.
Measured: Up to approximately 37.2 months
Number of Participants With Adverse Events of Special Interest (AESI) in Safety Population
AESI were defined as events of potential immunologic etiology, including immune-related AEs (irAEs).
Measured: Up to approximately 37.2 months
Number of Participants With AEs in Programmed Death Ligand-1 (PD-L1) Combined Positive Score (CPS ≥1) Population
Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells.
Measured: Up to approximately 37.2 months
Number of Participants With SAEs in PD-L1 CPS ≥1 Population
SAE was defined as any untoward medical occurrence that, at any dose, resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and other situations according to medical or scientific judgement. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells.
Measured: Up to approximately 37.2 months
Number of Participants With AESIs in PD-L1 CPS ≥1 Population
AESI were defined as events of potential immunologic etiology, including immune-related AEs (irAEs). CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells.
Measured: Up to approximately 37.2 months
Severity of AEs in Safety Population
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Severity for each AE was reported during the study and assigned a grade according to the NCI-CTCAE v5.0. from Grade 1 through Grade 5. Grade 1= mild toxicity; Grade 2 = moderate toxicity; Grade 3 = severe toxicity; Grade 4 = life-threatening or disabling toxicity, Grade 5 = death related to toxicity.
Measured: Up to approximately 37.2 months
Severity of SAEs in Safety Population
A SAE was defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, is a congenital anomaly/birth defect, any other situation such as important medical events according to medical or scientific judgement. Severity for each SAE was reported during the study and assigned a grade according to the NCI-CTCAE v5.0. from Grade 1 through Grade 5. Grade 1= mild toxicity; Grade 2 = moderate toxicity; Grade 3 = severe toxicity; Grade 4 = life-threatening or disabling toxicity, Grade 5 = death related to toxicity. Data of participants experiencing SAEs of Grade >= 3 has been presented.
Measured: Up to approximately 37.2 months
Severity of AESIs in Safety Population
AESI were defined as events of potential immunologic etiology, including immune-related AEs (irAEs). Severity of each AESI was reported during the study and was assigned a grade according to the NCI-CTCAE. AESIs severity were graded on a 5-point scale as: 1 = mild; discomfort noticed, but no disruption to daily activity, 2 = moderate; discomfort sufficient to reduce or affect normal daily activity, 3 = severe; inability to work or perform normal daily activity, 4 = life-threatening consequences and 5 = death related to AE. Data of participants experiencing AESIs of Grade >= 3 have been presented.
Measured: Up to approximately 37.2 months
Severity of AEs in PD-L1 CPS ≥1 Population
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Severity for each AE was reported during the study and assigned a grade according to the NCI-CTCAE v5.0. from Grade 1 through Grade 5. Grade 1= mild toxicity; Grade 2 = moderate toxicity; Grade 3 = severe toxicity; Grade 4 = life-threatening or disabling toxicity, Grade 5 = death related to toxicity. Data of participants experiencing AEs of Grade >= 3 have been presented. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells.
Measured: Up to approximately 37.2 months
Severity of SAEs in PD-L1 CPS ≥1 Population
A SAE was defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, is a congenital anomaly/birth defect, any other situation such as important medical events according to medical or scientific judgement. Severity for each SAE was reported during the study and assigned a grade according to the NCI-CTCAE v5.0. from Grade 1 through Grade 5. Grade 1= mild toxicity; Grade 2 = moderate toxicity; Grade 3 = severe toxicity; Grade 4 = life-threatening or disabling toxicity, Grade 5 = death related to toxicity. Data of participants that experienced SAEs of Grade >= 3 have been presented. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells.
Measured: Up to approximately 37.2 months
Severity of AESI in PD-L1 CPS ≥1 Population
AESI were defined as events of potential immunologic etiology, including immune-related AEs (irAEs). Severity of each AESI was reported during the study and was assigned a grade according to the NCI-CTCAE. AESIs severity were graded on a 5-point scale as: 1 = mild; discomfort noticed, but no disruption to daily activity, 2 = moderate; discomfort sufficient to reduce or affect normal daily activity, 3 = severe; inability to work or perform normal daily activity, 4 = life-threatening consequences and 5 = death related to AE. Data of participants that experienced AESIs of Grade >= 3 have been presented.
Measured: Up to approximately 37.2 months
Number of Participants With Dose Modifications in Safety Population
Number of participants with dose modifications (including dose interruptions, dose delays, dose reductions and treatment discontinuations) were reported by each interventional component.
Measured: Up to approximately 7 months
Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population
Number of participants with dose modifications (including dose interruptions, dose delays, dose reductions and treatment discontinuations) were reported by each interventional component. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells.
Measured: Up to approximately 7 months
Time to Deterioration (TTD) in Pain in mITT Population
TTD in pain is defined as the time from randomization to the first definitive meaningful deterioration from baseline in the European Organization for Research and Treatment of Cancer Item Library(EORTC IL51) Questionnaire pain domain, i.e. an increase from baseline of at least 8.33 observed at all subsequent non-missing visits. The EORTC Quality of Life Questionnaire 35-Item Head and Neck Module (QLQ-H\&N35) is a head and neck specific module with multi-item scales. The mouth pain, swallowing, speech problems, opening mouth, coughing, feeding tube, and trouble with social eating domains were administered and referred to as the EORTC IL51. The questionnaire scores for each scale and single-item measure are averaged and transformed linearly to present a score ranging from 0-100. A high score represents a high/healthy level of functioning. Kaplan-Meier estimate for the median TTD is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.
Measured: Up to approximately 7 months
TTD in Pain in PD-L1 CPS ≥1 Population
TTD in pain is defined as the time from randomization to the first definitive meaningful deterioration from baseline in the EORTC IL51 pain domain, i.e. an increase from baseline of at least 8.33 observed at all subsequent non-missing visits. The EORTC QLQ-H\&N35 is a head and neck specific module with multi-item scales. The mouth pain, swallowing, speech problems, opening mouth, coughing, feeding tube, and trouble with social eating domains were administered and referred to as the EORTC IL51. The questionnaire scores for each scale and single-item measure are averaged and transformed linearly to present a score ranging from 0-100. A high score represents a high/healthy level of functioning. Kaplan-Meier estimate for the median TTD is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells to the total number of viable tumor cells.
Measured: Up to approximately 7 months
TTD in Physical Function in mITT Population
TTD in physical function (PF) is defined as the time from randomization to the first definitive meaningful deterioration from baseline in the PF T-score, i.e. a decrease from baseline of at least 2.4 observed at all subsequent non-missing visits, as measured by the Patient-Reported Outcomes Measurement Information System - Physical Function (PROMIS PF 8c).The PROMIS PF 8c is an 8-item fixed length short form derived from the PROMIS Physical Function item bank. It includes a 5-point scale with three sets of response options. Scores on the PROMIS PF 8c are reported on a T score metric (mean = 50 and SD = 10), with higher scores reflecting better physical functioning.
Measured: Up to approximately 7 months
TTD in Physical Function in PD-L1 CPS ≥1 Population
TTD in PF is defined as the time from randomization to the first definitive meaningful deterioration from baseline in the PF T-score, i.e. a decrease from baseline of at least 2.4 observed at all subsequent non-missing visits, as measured by the PROMIS PF 8c.The PROMIS PF 8c is an 8-item fixed length short form derived from the PROMIS Physical Function item bank. It includes a 5-point scale with three sets of response options. Scores on the PROMIS PF 8c are reported on a T score metric (mean = 50 and SD = 10), with higher scores reflecting better physical functioning. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells
Measured: Up to approximately 7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start12 Aug 2020
- Primary completion27 Apr 2021
- Study completion19 Sep 2023
Why it stopped: The trial was stopped by the sponsor based on assessment of the clinical data
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neoplasms, Head and NeckStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This will be a randomized, parallel group treatment study with eligible participants receiving either GSK3359609 in combination with pembrolizumab and 5FU-platinum chemotherapy or placebo in combination with pembrolizumab and 5FU-platinum chemotherapy.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 117 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04428333
- Sponsor's protocol ID
- 209227
- Other IDs
- 2019-003981-42, 2019
- Acronym
- INDUCE-4
- Status last verified
- Sep 2024
- First submitted
- 9 Jun 2020
- Last updated
- 9 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04428333
- Acronym / sponsor ID
- INDUCE-4 / 209227
- Conditions
- Neoplasms, Head and Neck
- Keywords
- GSK3359609, Pembrolizumab, Programmed cell death receptor 1, Inducible T cell co-stimulatory receptor, Keynote-A02, Phase II/III, Platinum-based chemotherapy, 5FU
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The trial was stopped by the sponsor based on assessment of the clinical data
- Enrolment
- 117 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 12 Aug 2020 (actual)
- Primary completion
- 27 Apr 2021 (actual)
- Study completion
- 19 Sep 2023 (actual)
- First posted
- 11 Jun 2020 (actual)
- Results
- Posted 25 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- This will be a randomized, parallel group treatment study with eligible participants receiving either GSK3359609 in combination with pembrolizumab and 5FU-platinum chemotherapy or placebo in combination with pembrolizumab and 5FU-platinum chemotherapy.
| Arm | Type | Receives |
|---|---|---|
| Feladilimab + Pembrolizumab + 5-FU-platinum chemotherapy | Experimental | Drug: Feladilimab, Drug: Pembrolizumab, Drug: Platinum based chemotherapy, Drug: Fluorouracil (5FU) |
| Placebo + Pembrolizumab + 5-FU-platinum chemotherapy | Placebo comparator | Drug: Pembrolizumab, Drug: Placebo, Drug: Platinum based chemotherapy, Drug: Fluorouracil (5FU) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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).
Key exclusion criteria (26 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FeladilimabHumanized anti-inducible T cell co-stimulatory receptor (ICOS) immunoglobulin G4 (IgG4) monoclonal antibody (mAb) | Drug | Feladilimab + Pembrolizumab + 5-FU-platinum chemotherapy |
| PembrolizumabHumanized anti- programmed cell death receptor1 (anti-PD-1) IgG4 mAb | Drug | Feladilimab + Pembrolizumab + 5-FU-platinum chemotherapy, Placebo + Pembrolizumab + 5-FU-platinum chemotherapy |
| PlaceboSterile normal saline | Drug | Placebo + Pembrolizumab + 5-FU-platinum chemotherapy |
| Platinum based chemotherapyCisplatin/carboplatin | Drug | Feladilimab + Pembrolizumab + 5-FU-platinum chemotherapy, Placebo + Pembrolizumab + 5-FU-platinum chemotherapy |
| Fluorouracil (5FU)5-fluorouracil | Drug | Feladilimab + Pembrolizumab + 5-FU-platinum chemotherapy, Placebo + Pembrolizumab + 5-FU-platinum chemotherapy |
Primary outcome
Overall Survival (OS) in mITT Population
Time frame: Up to approximately 7 months
OS was defined as the time from the date of randomization to the date of death due to any cause. Kaplan-Meier estimate for the median OS is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.
OS in Programmed Death Receptor-ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Population
Time frame: Up to approximately 7 months
OS was defined as the time from the date of randomization until the date of death due to any cause. CPS was defined as the ratio of the combined number of PD-L1 expressing tumor cells and immune cells (lymphocytes and macrophages) to the total number of viable tumor cells. Kaplan-Meier estimate for the median OS is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 in mITT Population
Time frame: Up to approximately 7 months
PFS per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 was defined as the time from the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurs first. Kaplan-Meier estimate for the median PFS is presented, along with associated 95% confidence interval, estimated using the Brookmeyer-Crowley method.
27 secondary outcomes
PFS Per RECIST v1.1 in the PD-L1 CPS ≥1 Population
Time frame: Up to approximately 7 months
Milestone OS Rate at 12, 24 and 36 Months in mITT Population
Time frame: Months 12, 24 and 36
Milestone OS Rate at 12, 24 and 36 Months in PD-L1 CPS ≥1 Population
Time frame: Months 12, 24 and 36
Overall Response Rate (ORR) Per RECIST v1.1 in mITT Population
Time frame: Up to approximately 7 months
ORR Per RECIST v1.1 in PD-L1 CPS ≥1 Population
Time frame: Up to approximately 7 months
Disease Control Rate (DCR) Per RECIST v1.1 in mITT Population
Time frame: Up to approximately 7 months
DCR Per RECIST v1.1 in PD-L1 CPS ≥1 Population
Time frame: Up to approximately 7 months
Duration of Response (DoR) Per RECIST v1.1 in mITT Population
Time frame: Up to approximately 7 months
DoR Per RECIST v1.1 in PD-L1 CPS ≥1 Population
Time frame: Up to approximately 7 months
Number of Participants With Adverse Events (AEs) in Safety Population
Time frame: Up to approximately 37.2 months
Number of Participants With Serious Adverse Events (SAEs) in Safety Population
Time frame: Up to approximately 37.2 months
Number of Participants With Adverse Events of Special Interest (AESI) in Safety Population
Time frame: Up to approximately 37.2 months
Number of Participants With AEs in Programmed Death Ligand-1 (PD-L1) Combined Positive Score (CPS ≥1) Population
Time frame: Up to approximately 37.2 months
Number of Participants With SAEs in PD-L1 CPS ≥1 Population
Time frame: Up to approximately 37.2 months
Number of Participants With AESIs in PD-L1 CPS ≥1 Population
Time frame: Up to approximately 37.2 months
Severity of AEs in Safety Population
Time frame: Up to approximately 37.2 months
Severity of SAEs in Safety Population
Time frame: Up to approximately 37.2 months
Severity of AESIs in Safety Population
Time frame: Up to approximately 37.2 months
Severity of AEs in PD-L1 CPS ≥1 Population
Time frame: Up to approximately 37.2 months
Severity of SAEs in PD-L1 CPS ≥1 Population
Time frame: Up to approximately 37.2 months
Severity of AESI in PD-L1 CPS ≥1 Population
Time frame: Up to approximately 37.2 months
Number of Participants With Dose Modifications in Safety Population
Time frame: Up to approximately 7 months
Number of Participants With Dose Modifications in PD-L1 CPS ≥1 Population
Time frame: Up to approximately 7 months
Time to Deterioration (TTD) in Pain in mITT Population
Time frame: Up to approximately 7 months
TTD in Pain in PD-L1 CPS ≥1 Population
Time frame: Up to approximately 7 months
TTD in Physical Function in mITT Population
Time frame: Up to approximately 7 months
TTD in Physical Function in PD-L1 CPS ≥1 Population
Time frame: Up to approximately 7 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
71 sites in 19 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Feladilimab, Pembrolizumab and Platinum based chemotherapy in people with Neoplasms, Head and Neck, run by GlaxoSmithKline at 71 sites in 19 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 71 sites in Canada, Italy, Poland, Romania, South Korea and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS) in mITT Population (time frame: Up to approximately 7 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2024.