Clinical trial NCT04655976: Efficacy Comparison of Cobolimab + Dostarlimab + Docetaxel to Dostarlimab + Docetaxel to Docetaxel Alone in Participants With Advanced Non-small Cell Lung Cancer Who Have Progressed on Prior Anti-PD-(L)1 Therapy and Chemotherapy
Official title: A Randomized, Open Label Phase 2/3 Study Comparing Cobolimab + Dostarlimab + Docetaxel To Dostarlimab + Docetaxel To Docetaxel Alone In Participants With Advanced Non-small Cell Lung Cancer Who Have Progressed On Prior Anti-PD-(L)1 Therapy And Chemotherapy (COSTAR Lung)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Lung Cancer, Non-Small Cell
Keywords: GSK4069889A
GSK4057190A
Cobolimab
Dostarlimab
Docetaxel
Chemotherapy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2020-12-07
Enrollment: 758
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-center, parallel group treatment, Phase 2/3 open label study evaluating cobolimab in combination with dostarlimab and docetaxel in participants with advanced non-small cell Lung Cancer (NSCLC) who have progressed on prior anti-PD-(L)1 therapy and chemotherapy.


Eligibility criteria: Inclusion Criteria:

* Participant has histologically or cytologically proven advanced or metastatic NSCLC and only squamous or non-squamous cell carcinoma.
* Participant has received no more than 2 prior lines of therapy for advanced or metastatic disease, which must only include a platinum based (e.g., cisplatin, carboplatin) doublet chemotherapy regimen and an anti-PD-1 or an anti-PD-(L)1 antibody.
* Participant has measurable disease.
* Participant has documented radiographic disease progression on prior platinum based chemotherapy and on or after prior anti-PD-(L)1 therapy.
* Participant agrees to submit an archival formalin-fixed paraffin-embedded (FFPE) tumor tissue specimen that was collected on or after diagnosis of metastatic disease. If archival tissue is not available, the participant must undergo biopsy prior to study entry.
* Participant has an ECOG performance status score of 0 or 1.
* Participant has a life expectancy of at least 3 months.
* Participant has adequate Baseline organ function.
* Participant has recovered from any prior treatment related toxicities.
* Participant agrees to use contraception.

Exclusion Criteria:

* Participant has been previously treated with an anti-PD-\[L\]1 or anti-programmed death-ligand 2 (anti-PD-\[L\]2) agent that resulted in permanent discontinuation due to an AE.
* Participant has been previously treated with an anti-T cell immunoglobulin and mucin domain containing 3 (anti-TIM-3) or anti-cytotoxic T lymphocyte associated protein 4 (CTLA 4) agent or docetaxel.
* Participant has a documented sensitizing epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or c-ros oncogene 1 (ROS-1) mutation. Participants whose tumors have not been tested for these driver mutations and therefore who have unknown driver mutation status are not eligible. Participants with squamous histology do not need to be tested for these driver mutations.
* Participant had radiological or clinical disease progression (i.e., worsening performance status, clinical symptoms, and laboratory data) \<=8 weeks after initiation of prior anti-programmed cell death protein 1 (anti-PD-1) or anti-PD-L1 antibody. The clinical disease progression should have been confirmed by a subsequent radiological scan.
* Participant has received radiation to the lung that is \>30 gray (Gy) within 6 months prior to the first dose of study treatment.
* Participant has completed palliative radiotherapy within 7 days prior to the first dose of study treatment.
* Participant is ineligible if any of the following hepatic characteristics are present: a. Alanine aminotransferase (ALT) \>2.5 times upper limit normal (ULN) b. ALT and/or aspartate aminotransferase (AST) \>1.5 times ULN concomitant with alkaline phosphatase (ALP) \>2.5 times ULN; c. Bilirubin \>1 times ULN; d. Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease per the Investigator's assessment).
* Participant has known new or progressive brain metastases and/or leptomeningeal metastases. Participants who have received prior therapy for their brain metastases and have radiographically stable central nervous system disease may participate, provided they are neurologically stable for at least 4 weeks before study entry and are off corticosteroids within 3 days prior to the first dose of study treatment.
* Participant has tested positive for the following at Screening or within 3 months before the first dose of study treatment: a. Presence of hepatitis B surface antigen. b. Presence of hepatitis C antibody in the absence of a ribonucleic acid (RNA) test for hepatitis C virus. If a confirmatory RNA test is available, a positive test result will exclude a participant, while a negative test result (indicating absence of active infection) will allow the participant to enter into the study.
* Participant has known human immunodeficiency virus (HIV) (positive for HIV 1 or HIV 2 antibodies).
* Participant has active autoimmune disease that required systemic treatment in the past 2 years, is immunocompromised in the opinion of the Investigator, or is receiving systemic immunosuppressive treatment.
* Participant has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment of these conditions (including therapeutic thoracentesis or paracentesis) is eligible.
* Participant has current interstitial lung disease, current pneumonitis, or a history of pneumonitis that required the use of glucocorticoids to assist with management.
* Participant has pre-existing peripheral neuropathy that is Grade \>=2 by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 criteria.
* Participant has received a live vaccine within 30 days of the first dose of study treatment. Seasonal flu vaccines that do not contain live virus and Coronavirus Disease 2019 (COVID-19) vaccines.
* Participant is unable to interrupt aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) for undergoing a biopsy procedure (in cases when a participant does not have an archival biopsy), other than an aspirin dose \<=1.3 grams (g) per day, for a 5-day period (8-day) period for long-acting agents, such as piroxicam).

Primary outcomes:
measure: Overall survival (OS) in participants receiving cobolimab + dostarlimab + docetaxel relative to participants receiving docetaxel alone
timeFrame: Up to approximately 52 months
measure: OS in participants receiving dostarlimab + docetaxel relative to participants receiving docetaxel alone
timeFrame: Up to approximately 52 months
Secondary outcomes:
measure: OS in participants receiving cobolimab + dostarlimab + docetaxel relative to participants receiving dostarlimab + docetaxel
timeFrame: Up to approximately 52 months
measure: Objective response rate (ORR)
timeFrame: Up to approximately 52 months
measure: Progression free survival (PFS)
timeFrame: Up to approximately 52 months
measure: Duration of response (DOR)
timeFrame: Up to approximately 52 months
measure: Time to deterioration (TTD)
timeFrame: Up to approximately 52 months
measure: Change from Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 item Core Module (EORTC QLQ-C30) assessment
timeFrame: Baseline (Day 1) and up to approximately 52 months
measure: Change from Baseline in the EORTC QLQ LC13 assessment
timeFrame: Baseline (Day 1) and up to approximately 52 months
measure: Number of participants with serious adverse events (SAEs)
timeFrame: From consent signature (Day -28) until the 90 day post last dose follow-up
measure: Number of participants with treatment-emergent adverse events (TEAEs) and immune related adverse event (irAEs)
timeFrame: From consent signature (Day -28) until the 30 day post last dose follow-up
measure: Number of participants with TEAEs leading to death
timeFrame: From consent signature (Day -28) until the 90 day post last dose follow-up
measure: Number of participants with adverse events (AEs) leading to discontinuation
timeFrame: From consent signature (Day -28) until the 30 day post last dose follow-up
measure: Number of participants with clinically significant changes in hematology, clinical chemistry, thyroid function and urinalysis lab parameters
timeFrame: From consent signature (Day -28) until the 90 day post last dose follow-up
measure: Number of participants with clinically significant changes in vital signs and Electrocardiogram (ECG) Parameters
timeFrame: From consent signature (Day -28) until the 90 day post last dose follow-up
measure: Number of participants with indicated Eastern Cooperative Oncology Group (ECOG) performance status
timeFrame: From consent signature (Day -28) until the 90 day post last dose follow-up
measure: Number of participants with usage of concomitant medications
timeFrame: From consent signature (Day -28) until the 90 day post last dose follow-up
measure: Number of participants with abnormal physical examinations
timeFrame: From consent signature (Day -28) until the 90 day post last dose follow-up
Other outcomes:
Locations:
city: Fountain Valley
country: United States
facility: GSK Investigational Site
state: California
city: Walnut Creek
country: United States
facility: GSK Investigational Site
state: California
city: Norwich
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Honolulu
country: United States
facility: GSK Investigational Site
state: Hawaii
city: Iowa City
country: United States
facility: GSK Investigational Site
state: Iowa
city: Edgewood
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Mineola
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: White Plains
country: United States
facility: GSK Investigational Site
state: New York
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Sioux Falls
country: United States
facility: GSK Investigational Site
state: South Dakota
city: Houston
country: United States
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state: Texas
city: Fredericksburg
country: United States
facility: GSK Investigational Site
state: Virginia
city: Tacoma
country: United States
facility: GSK Investigational Site
state: Washington
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Cipoletti Rio Negro
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: GSK Investigational Site
city: Florida
country: Argentina
facility: GSK Investigational Site
city: La Rioja
country: Argentina
facility: GSK Investigational Site
city: Pergamino
country: Argentina
facility: GSK Investigational Site
city: Rosario
country: Argentina
facility: GSK Investigational Site
city: Viedma
country: Argentina
facility: GSK Investigational Site
city: South Brisbane
country: Australia
facility: GSK Investigational Site
state: Queensland
city: Ashford
country: Australia
facility: GSK Investigational Site
state: South Australia
city: Hobart
country: Australia
facility: GSK Investigational Site
state: Tasmania
city: Ballarat
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Melbourne
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Mount Waverley
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Aalst
country: Belgium
facility: GSK Investigational Site
city: Hasselt
country: Belgium
facility: GSK Investigational Site
city: Kortrijk
country: Belgium
facility: GSK Investigational Site
city: Blumenau
country: Brazil
facility: GSK Investigational Site
city: Fortaleza
country: Brazil
facility: GSK Investigational Site
city: Porto Alegre
country: Brazil
facility: GSK Investigational Site
city: Rio de Janeiro
country: Brazil
facility: GSK Investigational Site
city: Rio de Janeiro
country: Brazil
facility: GSK Investigational Site
city: Salvador
country: Brazil
facility: GSK Investigational Site
city: SAo Paulo
country: Brazil
facility: GSK Investigational Site
city: Kingston
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Oshawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Sudbury
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Greenfield Park
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Kuopio
country: Finland
facility: GSK Investigational Site
city: CrEteil cedex
country: France
facility: GSK Investigational Site
city: Grenoble cedex 9
country: France
facility: GSK Investigational Site
city: Marseille
country: France
facility: GSK Investigational Site
city: Nice Cedex 2
country: France
facility: GSK Investigational Site
city: Quimper cedex
country: France
facility: GSK Investigational Site
city: Rennes
country: France
facility: GSK Investigational Site
city: Tours cedex 9
country: France
facility: GSK Investigational Site
city: Augsburg
country: Germany
facility: GSK Investigational Site
city: Bad Berka
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
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city: Bonn
country: Germany
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city: Dresden
country: Germany
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city: Essen
country: Germany
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city: Frankfurt
country: Germany
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city: Frankfurt
country: Germany
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city: Halle
country: Germany
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city: Heidelberg
country: Germany
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city: Karlsruhe
country: Germany
facility: GSK Investigational Site
city: Koeln
country: Germany
facility: GSK Investigational Site
city: Muenchen
country: Germany
facility: GSK Investigational Site
city: MUnchen
country: Germany
facility: GSK Investigational Site
city: Oldenburg
country: Germany
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Athens
country: Greece
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city: Athens
country: Greece
facility: GSK Investigational Site
city: Larissa
country: Greece
facility: GSK Investigational Site
city: Pylaia Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Rio Patras
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Ancona
country: Italy
facility: GSK Investigational Site
city: Avellino
country: Italy
facility: GSK Investigational Site
city: Firenze
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
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city: Milano
country: Italy
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city: Monza
country: Italy
facility: GSK Investigational Site
city: Napoli
country: Italy
facility: GSK Investigational Site
city: Orbassano TO
country: Italy
facility: GSK Investigational Site
city: Perugia
country: Italy
facility: GSK Investigational Site
city: Siena
country: Italy
facility: GSK Investigational Site
city: Kyoto
country: Japan
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city: Miyagi
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Yamaguchi
country: Japan
facility: GSK Investigational Site
city: Cheongju Chungcheongbuk-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Daegu
country: Korea, Republic of
facility: GSK Investigational Site
city: Gyeonggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Pusan
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: Suwon Kyunggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Guadalajara
country: Mexico
facility: GSK Investigational Site
city: Mexico City
country: Mexico
facility: GSK Investigational Site
city: Mexico City
country: Mexico
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city: Mexico City
country: Mexico
facility: GSK Investigational Site
city: Mexico City
country: Mexico
facility: GSK Investigational Site
city: Monterrey
country: Mexico
facility: GSK Investigational Site
city: Puebla Puebla
country: Mexico
facility: GSK Investigational Site
city: Amersfoort
country: Netherlands
facility: GSK Investigational Site
city: Enschede
country: Netherlands
facility: GSK Investigational Site
city: Groningen
country: Netherlands
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city: Harderwijk
country: Netherlands
facility: GSK Investigational Site
city: Nijmegen
country: Netherlands
facility: GSK Investigational Site
city: Utrecht
country: Netherlands
facility: GSK Investigational Site
city: Zwolle
country: Netherlands
facility: GSK Investigational Site
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Gdynia
country: Poland
facility: GSK Investigational Site
city: Lodz
country: Poland
facility: GSK Investigational Site
city: Olsztyn
country: Poland
facility: GSK Investigational Site
city: Pila
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
city: Bucuresti
country: Romania
facility: GSK Investigational Site
city: Craiova Dolj
country: Romania
facility: GSK Investigational Site
city: Craiova
country: Romania
facility: GSK Investigational Site
city: Otopeni
country: Romania
facility: GSK Investigational Site
city: Timisoara
country: Romania
facility: GSK Investigational Site
city: Chelyabinsk
country: Russian Federation
facility: GSK Investigational Site
city: Moscow Region
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: A CoruNa
country: Spain
facility: GSK Investigational Site
city: Badalona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Burgos
country: Spain
facility: GSK Investigational Site
city: Cordoba
country: Spain
facility: GSK Investigational Site
city: Las Palmas De Gran Canar
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Malaga
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Gavle
country: Sweden
facility: GSK Investigational Site
city: Stockholm
country: Sweden
facility: GSK Investigational Site
city: Uppsala
country: Sweden
facility: GSK Investigational Site
city: HsinChu
country: Taiwan
facility: GSK Investigational Site
city: Taichung
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Bangkok
country: Thailand
facility: GSK Investigational Site
city: Dusit
country: Thailand
facility: GSK Investigational Site
city: Kho Hong Hat Yai
country: Thailand
facility: GSK Investigational Site
city: Khon Kaen
country: Thailand
facility: GSK Investigational Site
city: Pathumthani
country: Thailand
facility: GSK Investigational Site
city: Adana
country: Turkey
facility: GSK Investigational Site
city: Antalya
country: Turkey
facility: GSK Investigational Site
city: Izmir
country: Turkey
facility: GSK Investigational Site
city: Cardiff
country: United Kingdom
facility: GSK Investigational Site
city: Edinburgh
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Manchester
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: