Clinical trial NCT04128696: Study of GSK3359609 and Pembrolizumab in Programmed Death Receptor 1-ligand 1 (PD-L1) Positive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Official title: A Randomized, Double-blind, Adaptive, Phase II/III Study of GSK3359609 or Placebo in Combination With Pembrolizumab for First-Line Treatment of PD-L1 Positive Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Neoplasms, Head and Neck
Keywords: GSK3359609
Pembrolizumab
Programmed death receptor 1-ligand 1
Head and neck squamous cell carcinoma/cancer
Inducible T cell co-stimulatory receptor
Keynote-A01
Head & neck
Phase III
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2019-10-16
Enrollment: 315
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This will be a randomized, parallel group treatment study with eligible participants receiving GSK3359609 plus pembrolizumab or placebo plus pembrolizumab.
Primary purpose: TREATMENT

Brief summary: The purpose of study is to evaluate if the addition of GSK3359609 to pembrolizumab as first-line treatment improves the efficacy of pembrolizumab in participants with recurrent or metastatic (R/M) head and neck squamous cell carcinoma/cancer (HNSCC).This is a randomized, double-blind, adaptive Phase II/III study comparing a combination of GSK3359609 inducible T cell co-stimulatory receptor (ICOS) agonist and pembrolizumab to pembrolizumab plus placebo in participants with programmed death receptor 1-ligand 1 (PD-L1) combined positive score (CPS) \>=1 R/M HNSCC.


Eligibility criteria: Inclusion Criteria:

* Capable of giving signed informed consent
* Male or female, age \>=18 years
* Histological or cytological documentation of Head and Neck Squamous Cell Carcinoma (HNSCC) that is 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 (except for systemic therapy given as part of multimodal treatment for locally advanced disease)
* Measurable disease per RECIST version 1.1 guidelines
* ECOG Performance 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 at least one of the following conditions apply:

  1. Not a woman of childbearing potential (WOCBP)
  2. A WOCBP who agrees to use a 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 period
* 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 Immunohistochemistry (IHC) CPS 1 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 and/or anti-ICOS directed agent
* Systemic approved or investigational anticancer therapy within 30 days or 5 half-lives of the drug, whichever is shorter
* Major surgery 28 days prior to randomization
* Has high risk of bleeding
* 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, except as noted below:

  a. Any other invasive malignancy for which the participant was definitively treated, has been disease-free for 3 years and in the opinion of the principal investigator and GSK Medical Monitor will not affect the evaluation of the effects of the study treatment on the currently targeted malignancy, may be included in this clinical study
* Autoimmune disease or syndrome that required systemic treatment within the past 2 years
* Has a diagnosis of immunodeficiency or is receiving systemic steroids (≥10 mg oral prednisone per day 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
* Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice
* Active infection requiring systemic therapy
* Known 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 any ingredient used in the study treatment formulations
* Known history of active tuberculosis
* Any serious and/or unstable pre-existing medical (aside from malignancy), 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 (unless in follow-up phase and 4 weeks have elapsed from last dose of prior investigational agent), or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to date of randomization
* Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study

Primary outcomes:
measure: Overall Survival (OS) in the Programmed Death Receptor-ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Population
timeFrame: Up to approximately 16 months
measure: OS in the PD-L1 Expression High (CPS ≥20) Population
timeFrame: Up to approximately 16 months
measure: Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) in the PD-L1 CPS ≥1 Population
timeFrame: Up to approximately 16 months
Secondary outcomes:
measure: PFS Per Immune-based RECIST (iRECIST) in the PD-L1 CPS ≥1 Population
timeFrame: Up to approximately 16 months
measure: PFS Per RECIST in the PD-L1 CPS ≥20 Population
timeFrame: Up to approximately 16 months
measure: PFS Per iRECIST (iPFS) in the PD-L1 CPS ≥20 Population
timeFrame: Up to approximately 16 months
measure: Milestone OS Rate at 12 Months in the PD-L1 CPS ≥1 Population
timeFrame: 12 months
measure: Milestone OS Rate at 24 Months in the PD-L1 CPS ≥1 Population
timeFrame: 24 months
measure: Milestone OS Rate at 12 Months in the PD-L1 CPS ≥20 Population
timeFrame: 12 months
measure: Milestone OS Rate at 24 Months in the PD-L1 CPS ≥20 Population
timeFrame: 24 months
measure: Overall Response Rate (ORR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population
timeFrame: Up to approximately 16 months
measure: ORR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population
timeFrame: Up to approximately 16 months
measure: Disease Control Rate (DCR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population
timeFrame: Up to approximately 16 months
measure: DCR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population
timeFrame: Up to approximately 16 months
measure: Duration of Response (DoR) Per RECIST v1.1 in the PD-L1 CPS ≥1 Population
timeFrame: Up to approximately 16 months
measure: DoR Per RECIST v1.1 in the PD-L1 CPS ≥20 Population
timeFrame: Up to approximately 16 months
measure: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to approximately 43 months
measure: Number of Participants With AEs by Severity
timeFrame: Up to approximately 43 months
measure: Number of Participants With SAEs by Severity
timeFrame: Up to approximately 43 months
measure: Number of Participants With Adverse Events of Special Interest (AESI)
timeFrame: Up to approximately 43 months
measure: Number of Participants With AESI by Severity
timeFrame: Up to approximately 43 months
measure: Number of Participants With Dose Modifications
timeFrame: Up to approximately 16 months
measure: Time to Deterioration (TTD) in Pain in the PD-L1 CPS ≥1 Population
timeFrame: Up to approximately 16 months
measure: TTD in Pain in the PD-L1 CPS ≥20 Population
timeFrame: Up to approximately 16 months
measure: TTD in Physical Function in the PD-L1 CPS ≥1 Population
timeFrame: Up to approximately 16 months
measure: TTD in Physical Function in the PD-L1 CPS ≥20 Population
timeFrame: Up to approximately 16 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: GSK Investigational Site
state: California
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Saint Petersburg
country: United States
facility: GSK Investigational Site
state: Florida
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Charlotte
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Chattanooga
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: La Plata
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: San Juan
country: Argentina
facility: GSK Investigational Site
city: Blacktown
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: St Leonards
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Herston
country: Australia
facility: GSK Investigational Site
state: Queensland
city: Heidelberg
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Melbourne
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Nedlands
country: Australia
facility: GSK Investigational Site
state: Western Australia
city: Darlinghurst
country: Australia
facility: GSK Investigational Site
city: Vitória
country: Brazil
facility: GSK Investigational Site
state: Espírito Santo
city: Florianopolis
country: Brazil
facility: GSK Investigational Site
state: Santa Catarina
city: Barretos
country: Brazil
facility: GSK Investigational Site
state: São Paulo
city: Sao Jose do Rio Preto
country: Brazil
facility: GSK Investigational Site
state: São Paulo
city: Belo Horizonte, Minas Gerais
country: Brazil
facility: GSK Investigational Site
city: São Paulo
country: Brazil
facility: GSK Investigational Site
city: São Paulo
country: Brazil
facility: GSK Investigational Site
city: Calgary
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Edmonton
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Vancouver
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Hamilton
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Quebec City
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Rimouski
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Guangzhou
country: China
facility: GSK Investigational Site
state: Guangdong
city: Guangzhou
country: China
facility: GSK Investigational Site
state: Guangdong
city: Nanning
country: China
facility: GSK Investigational Site
state: Guangxi
city: Guiyang
country: China
facility: GSK Investigational Site
state: Guizhou
city: Wuhan
country: China
facility: GSK Investigational Site
state: Hubei
city: Nanchang
country: China
facility: GSK Investigational Site
state: Jiangxi
city: Chengdu
country: China
facility: GSK Investigational Site
state: Sichuan
city: Chengdu
country: China
facility: GSK Investigational Site
state: Sichuan
city: Bengbu
country: China
facility: GSK Investigational Site
city: Harbin
country: China
facility: GSK Investigational Site
city: Hefei
country: China
facility: GSK Investigational Site
city: Shnghai
country: China
facility: GSK Investigational Site
city: Copenhagen
country: Denmark
facility: GSK Investigational Site
city: Bordeaux
country: France
facility: GSK Investigational Site
city: Epagny Metz-Tessy
country: France
facility: GSK Investigational Site
city: Le Mans
country: France
facility: GSK Investigational Site
city: Lille
country: France
facility: GSK Investigational Site
city: Lyon cedex 08
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Saint Herblain cedex
country: France
facility: GSK Investigational Site
city: Strasbourg
country: France
facility: GSK Investigational Site
city: Toulouse Cedex 9
country: France
facility: GSK Investigational Site
city: Valenciennes Cedex
country: France
facility: GSK Investigational Site
city: Ulm
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Aachen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Heraklion,Crete
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Dublin
country: Ireland
facility: GSK Investigational Site
city: Dublin
country: Ireland
facility: GSK Investigational Site
city: Jerusalem
country: Israel
facility: GSK Investigational Site
city: Petah Tikva
country: Israel
facility: GSK Investigational Site
city: Ramat Gan
country: Israel
facility: GSK Investigational Site
city: Meldola (FC)
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Brescia
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Candiolo
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Legnago (VR)
country: Italy
facility: GSK Investigational Site
state: Veneto
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Ehime
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Iwate
country: Japan
facility: GSK Investigational Site
city: Kagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Miyagi
country: Japan
facility: GSK Investigational Site
city: Niigata
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Shizuoka
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Busan
country: Korea, Republic of
facility: GSK Investigational Site
city: Hwasun,Jeollanam-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Incheon
country: Korea, Republic of
facility: GSK Investigational Site
city: Seongnam-si, Gyeonggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul,
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Saltillo
country: Mexico
facility: GSK Investigational Site
state: Coahuila
city: Guadalajara
country: Mexico
facility: GSK Investigational Site
state: Jalisco
city: Maastricht
country: Netherlands
facility: GSK Investigational Site
city: Rotterdam
country: Netherlands
facility: GSK Investigational Site
city: Bergen
country: Norway
facility: GSK Investigational Site
city: Oslo
country: Norway
facility: GSK Investigational Site
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Gdynia
country: Poland
facility: GSK Investigational Site
city: Gliwice
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Olsztyn
country: Poland
facility: GSK Investigational Site
city: Tomaszow Mazowiecki
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Coimbra
country: Portugal
facility: GSK Investigational Site
city: Lisboa
country: Portugal
facility: GSK Investigational Site
city: Matosinhos
country: Portugal
facility: GSK Investigational Site
city: Porto
country: Portugal
facility: GSK Investigational Site
city: Porto
country: Portugal
facility: GSK Investigational Site
city: Brasov
country: Romania
facility: GSK Investigational Site
city: Bucuresti
country: Romania
facility: GSK Investigational Site
city: Cluj Napoca
country: Romania
facility: GSK Investigational Site
city: Cluj-Napoca
country: Romania
facility: GSK Investigational Site
city: Constanta
country: Romania
facility: GSK Investigational Site
city: Craiova
country: Romania
facility: GSK Investigational Site
city: Floresti
country: Romania
facility: GSK Investigational Site
city: Iasi
country: Romania
facility: GSK Investigational Site
city: Oradea
country: Romania
facility: GSK Investigational Site
city: Otopeni
country: Romania
facility: GSK Investigational Site
city: Satu Mare
country: Romania
facility: GSK Investigational Site
city: Suceava
country: Romania
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Poselok Kuzmolovsky
country: Russian Federation
facility: GSK Investigational Site
city: Pushkin
country: Russian Federation
facility: GSK Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Yaroslavl
country: Russian Federation
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Málaga
country: Spain
facility: GSK Investigational Site
city: Pozuelo De Alarcón/Madrid
country: Spain
facility: GSK Investigational Site
city: Santiago de Compostela
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Zaragoza
country: Spain
facility: GSK Investigational Site
city: St Gallen
country: Switzerland
facility: GSK Investigational Site
city: Zuerich
country: Switzerland
facility: GSK Investigational Site
city: Changhua
country: Taiwan
facility: GSK Investigational Site
city: Kaohsiung City
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taoyuan City
country: Taiwan
facility: GSK Investigational Site
city: Manchester
country: United Kingdom
facility: GSK Investigational Site
state: Lancashire
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Nottingham
country: United Kingdom
facility: GSK Investigational Site
city: Sutton
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: