Clinical trial NCT03088540: Study of REGN 2810 Compared to Platinum-Based Chemotherapies in Participants With Metastatic Non-Small Cell Lung Cancer (NSCLC)
Official title: A Global, Randomised, Phase 3, Open-label Study of REGN2810 (ANTI-PD 1 Antibody) Versus Platinum Based Chemotherapy in First Line Treatment of Patients With Advanced or Metastatic PD L1+Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma，Non-Small-Cell Lung
Lung Carcinomas, Non-Small-Cell
Non-small-cell Lung Carcinoma
Nonsmall Cell Lung Cancer
Keywords: Previous Smoker
Current Smoker
Stage IIIB
Stage IIIC
Stage IV
PD-L1
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2017-03-23
Enrollment: 712
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The primary objectives of the study are:

* To compare the overall survival (OS) of cemiplimab versus standard-of-care platinum-based chemotherapies in the first-line treatment of patients with advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 in ≥50% of tumor cells
* To compare the progression-free survival (PFS) of cemiplimab versus standard-of-care platinum-based chemotherapies in the first-line treatment of patients with advanced or metastatic NSCLC whose tumors express PD-L1 in ≥50% of tumor cells

The key secondary objective of the study is to compare the objective response rate (ORR) of cemiplimab versus platinum-based chemotherapies

Detailed description: There is option to join genomics sub-study.

Eligibility criteria: Key Inclusion Criteria:

A patient must meet the following criteria to be eligible for inclusion in the study:

1. Patients with histologically or cytologically documented squamous or non squamous NSCLC with stage IIIB or stage IIIC disease who are not candidates for treatment with definitive concurrent chemoradiation or patients with stage IV disease who received no prior systemic treatment for recurrent or metastatic NSCLC
2. Archival or newly obtained formalin-fixed tumor tissue from a metastatic/recurrent site, which has not previously been irradiated
3. Tumor cells expressing PD L1 above a specific percentage of tumor cells by IHC performed by the central laboratory
4. At least 1 radiographically measureable lesion per RECIST 1.1
5. ECOG performance status of ≤1
6. Anticipated life expectancy of at least 3 months
7. Adequate organ and bone marrow function

Key Exclusion Criteria:

A patient who meets any of the following criteria will be excluded from the study:

1. Patients that have never smoked, defined as smoking \<100 cigarettes in a lifetime
2. Active or untreated brain metastases or spinal cord compression
3. Patients with tumors tested positive for EGFR gene mutations, ALK gene translocations, or ROS1 fusions
4. Encephalitis, meningitis, or uncontrolled seizures in the year prior to randomization
5. History of interstitial lung disease (eg, idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis resolved ≥6 months prior to randomization
6. Patients with active, known, or suspected autoimmune disease that has required systemic therapy in the past 2 years
7. Patients with a condition requiring corticosteroid therapy (\>10 mg prednisone/day or equivalent) within 14 days of randomization
8. Another malignancy that is progressing or requires treatment
9. Uncontrolled infection with hepatitis B or hepatitis C or human immunodeficiency virus (HIV) or diagnosis of immunodeficiency
10. Active infection requiring systemic therapy within 14 days prior to randomization
11. Prior therapy with anti-PD 1 or anti-PD L1
12. Treatment-related immune-mediated AEs from immune-modulatory agents
13. Receipt of an investigational drug or device within 30 days
14. Receipt of a live vaccine within 30 days of planned start of study medication
15. Major surgery or significant traumatic injury within 4 weeks prior to first dose
16. Documented allergic or acute hypersensitivity reaction attributed to antibody treatments
17. Known psychiatric or substance abuse disorder that would interfere with participation with the requirements of the study, including current use of any illicit drugs
18. Pregnant or breastfeeding women
19. Women of childbearing potential or men who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose

Note: Other protocol defined Inclusion/Exclusion criteria apply.

Primary outcomes:
measure: Overall survival (OS)
timeFrame: From date of randomization until the date of death, assessed up to 68 months
measure: Progression-free survival (PFS) as assessed by a blinded Independent review committee (IRC) using RECIST 1.1
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 68 months
Secondary outcomes:
measure: Objective response rates (ORR)
timeFrame: From date of randomization to the date of the first objectively documented progression or the date of subsequent anti-cancer therapy, whichever comes first, up to 68 months
measure: Best overall response (BOR)
timeFrame: From date of randomization until the date of first documented progression or the date of subsequent anti-cancer therapy, whichever came first, assessed up to 68 months
measure: Compare the duration of response (DOR) of cemiplimab versus platinum based chemotherapies
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 68 months
measure: Change from baseline in quality of life (QoL) scores as assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
timeFrame: Baseline up to 26 months after treatment
measure: Change from baseline in in lung cancer symptom scores as measured by the EORTC Lung Cancer 13 (EORTC QLQ-LC13)
timeFrame: Baseline up to 26 months after treatment
measure: Incidence of Adverse Events (AEs)
timeFrame: Baseline up to 68 months after treatment
measure: Incidence of serious adverse events (SAEs)
timeFrame: Baseline up to 68 months after treatment
measure: Incidence of deaths
timeFrame: Baseline up to 68 months after treatment
measure: Incidence of laboratory abnormalities
timeFrame: Baseline up to 68 months after treatment
measure: Measure concentrations of cemiplimab in serum
timeFrame: Baseline up to 68 months after treatment
measure: Characterize the pharmacokinetics (PK) of cemiplimab
timeFrame: Baseline up to 68 months after treatment
Other outcomes:
Locations:
city: Albury
country: Australia
facility: Clinical Study Site
state: New South Wales
city: Wollongong
country: Australia
facility: Clinical Study Site
state: New South Wales
city: Fitzroy
country: Australia
facility: Clinical Study Site
city: Minsk
country: Belarus
facility: Clinical Study Site
city: Mogilev
country: Belarus
facility: Clinical Study Site
city: Porto Alegre
country: Brazil
facility: Clinical Study Site 1
state: Rio Grande Do Sul
city: Barretos
country: Brazil
facility: Clinical Study Site
city: Curitiba
country: Brazil
facility: Clinical Study Site
city: Joinville
country: Brazil
facility: Clinical Study Site
city: Lajeado
country: Brazil
facility: Clinical Study Site
city: Mogi Das Cruzes
country: Brazil
facility: Clinical Study Site
city: Passo Fundo
country: Brazil
facility: Clinical Study Site
city: Pelotas
country: Brazil
facility: Clinical Study Site
city: Porto Alegre
country: Brazil
facility: Clinical Study Site 2
city: Porto Alegre
country: Brazil
facility: Clinical Study Site 3
city: Recife
country: Brazil
facility: Clinical Study Site
city: Rio De Janeiro
country: Brazil
facility: Clinical Study Site
city: Salvador
country: Brazil
facility: Clinical Study Site
city: Santa Cecília
country: Brazil
facility: Clinical Study Site
city: Sao Paulo
country: Brazil
facility: Clinical Study Site #4
city: São José Do Rio Preto
country: Brazil
facility: Clinical Study Site
city: São Paulo
country: Brazil
facility: Clinical Study Site #3
city: São Paulo
country: Brazil
facility: Clinical Study Site 1
city: São Paulo
country: Brazil
facility: Clinical Study Site 2
city: Dobrich
country: Bulgaria
facility: Clinical Study Site
city: Gabrovo
country: Bulgaria
facility: Clinical Study Site
city: Recoleta
country: Chile
facility: Clinical Study Site
city: Santiago
country: Chile
facility: Clinical Study Site
city: Temuco
country: Chile
facility: Clinical Study Site
city: Viña Del Mar
country: Chile
facility: Clincial Study Site
city: Lanshan
country: China
facility: Clinical Study Site
state: Shandong
city: Guangdong
country: China
facility: Clinical Study Site
city: Harbin
country: China
facility: Clinical Study Site
city: Linyi
country: China
facility: Clinical Study Site
city: Shanghai
country: China
facility: Clinical Study Site 1
city: Shanghai
country: China
facility: Clinical Study Site 2
city: Tianjin
country: China
facility: Clinical Study Site 1
city: Tianjin
country: China
facility: Clinical Study Site 2
city: Xuzhou
country: China
facility: Clinical Study Site
city: Zhejiang
country: China
facility: Clinical Study Site
city: Barranquilla
country: Colombia
facility: Clinical Study Site
city: Bogotá
country: Colombia
facility: Clinical Study Site
city: Floridablanca
country: Colombia
facility: Clinical Study Site
city: Nový Jičín
country: Czechia
facility: Clinical Study Site
city: Pelhřimov
country: Czechia
facility: Clinical Study Site
city: Prague
country: Czechia
facility: Clinical Study Site
city: Praha
country: Czechia
facility: Clinical Study Site
city: Batumi
country: Georgia
facility: Clinical Study Site
city: Tbilisi
country: Georgia
facility: Clinical Study Site #6
city: Tbilisi
country: Georgia
facility: Clinical Study Site 1
city: Tbilisi
country: Georgia
facility: Clinical Study Site 2
city: Tbilisi
country: Georgia
facility: Clinical Study Site 3
city: Tbilisi
country: Georgia
facility: Clinical Study Site 4
city: Tbilisi
country: Georgia
facility: Clinical Study Site 5
city: Patras
country: Greece
facility: Clinical Study Site
state: Achaia
city: Cholargós
country: Greece
facility: Clinical Study Site
state: Attiki
city: Athens
country: Greece
facility: Clinical Study Site 1
city: Athens
country: Greece
facility: Clinical Study Site 2
city: Athens
country: Greece
facility: Clinical Study Site 3
city: Larissa
country: Greece
facility: Clinical Study Site
city: Pylaía
country: Greece
facility: Clinical Study Site
city: Thessaloníki
country: Greece
facility: Clinical Study Site 1
city: Thessaloníki
country: Greece
facility: Clinical Study Site 2
city: Thessaloníki
country: Greece
facility: Clinical Study Site 3
city: Gyula
country: Hungary
facility: Clinical Study Site
state: Bekes
city: Tatabánya
country: Hungary
facility: Clinical Study Site
state: Komarom-Esztergom
city: Farkasgyepű
country: Hungary
facility: Clinical Study Site
state: Veszprém
city: Budapest
country: Hungary
facility: Clinical Study Site
city: Debrecen
country: Hungary
facility: Clinical Study Site
city: Zalaegerszeg
country: Hungary
facility: Clinical Study Site
city: Amman
country: Jordan
facility: Clinical Study Site
city: Irbid
country: Jordan
facility: Clinical Study Site
city: Bsalîm
country: Lebanon
facility: Clinical Study Site
city: Mazraat Ech Choûf
country: Lebanon
facility: Clinical Study Site
city: Sidon
country: Lebanon
facility: Clinical Study Site
city: Kampung Baharu Nilai
country: Malaysia
facility: Clinical Study Site
city: Kuala Lumpur
country: Malaysia
facility: Clinical Study Site #1
city: Kuala Lumpur
country: Malaysia
facility: Clinical Study Site #2
city: Kuching
country: Malaysia
facility: Clinical Study Site
city: Pulau Pinang
country: Malaysia
facility: Clinical Study Site
city: Tanjong Bungah
country: Malaysia
facility: Clinical Study Site
city: Coahuila
country: Mexico
facility: Clinical Study Site
city: Cuautitlán
country: Mexico
facility: Clinical Study Site
city: Jalisco
country: Mexico
facility: Clinical Study Site
city: León de los Aldama
country: Mexico
facility: Clinical Study Site
city: Monterrey
country: Mexico
facility: Clinical Study Site 1
city: Monterrey
country: Mexico
facility: Clinical Study Site 2
city: Monterrey
country: Mexico
facility: Clinical Study Site 3
city: Oaxaca
country: Mexico
facility: Clinical Study Site
city: San Luis Potosí
country: Mexico
facility: Clinical Study Site
city: Bacolod City
country: Philippines
facility: Clinical Study Site
city: Batangas
country: Philippines
facility: Clinical Study Site
city: Cebu
country: Philippines
facility: Clinical Study Site
city: Davao City
country: Philippines
facility: Clinical Study Site
city: Manila
country: Philippines
facility: Clinical Study Site 1
city: Manila
country: Philippines
facility: Clinical Study Site 2
city: Quezon City
country: Philippines
facility: Clinical Study Site #1
city: Quezon City
country: Philippines
facility: Clinical Study Site #2
city: Taguig
country: Philippines
facility: Clinical Study Site
city: Dąbrowa Górnicza
country: Poland
facility: Clinical Study Site
city: Gdynia
country: Poland
facility: Clinical Study Site
city: Kraków
country: Poland
facility: Clinical Study Site
city: Olsztyn
country: Poland
facility: Clinical Study Site
city: Poznań
country: Poland
facility: Clinical Study Site
city: Prabuty
country: Poland
facility: Clinical Study Site
city: Radom
country: Poland
facility: Clinical Study Site
city: Rzeszów
country: Poland
facility: Clinical Study Site
city: Toruń
country: Poland
facility: Clinical Study Site
city: Warszawa
country: Poland
facility: Clinical Study Site
city: Wodzisław Śląski
country: Poland
facility: Clinical Study Site
city: Łódź
country: Poland
facility: Clinical Study Site
city: Craiova
country: Romania
facility: Clinical Study Site 1
city: Craiova
country: Romania
facility: Clinical Study Site 2
city: Floreşti
country: Romania
facility: Clinical Study Site
city: Ploieşti
country: Romania
facility: Clinical Study Site
city: Timişoara
country: Romania
facility: Clinical Study Site
city: Ufa
country: Russian Federation
facility: Clinical Study Site
state: Republic Bashkortost
city: Pushkin
country: Russian Federation
facility: Clinical Study Site
state: Saint Petersburg
city: Arkhangel'sk
country: Russian Federation
facility: Clinical Study Site
city: Belgorod
country: Russian Federation
facility: Clinical Study Site
city: Chelyabinsk
country: Russian Federation
facility: Clinical Study Site
city: Kaluga
country: Russian Federation
facility: Clinical Study Site
city: Kazan
country: Russian Federation
facility: Clinical Study Site
city: Kemerovo
country: Russian Federation
facility: Clinical Study Site
city: Kislino
country: Russian Federation
facility: Clinical Study Site
city: Kursk
country: Russian Federation
facility: Clinical Study Site
city: Moscow
country: Russian Federation
facility: Clinical Study Site 1
city: Moscow
country: Russian Federation
facility: Clinical Study Site 2
city: Moscow
country: Russian Federation
facility: Clinical Study Site 3
city: Omsk
country: Russian Federation
facility: Clinical Study Site
city: Pyatigorsk
country: Russian Federation
facility: Clinical Study Site
city: Saint Petersburg
country: Russian Federation
facility: Clinical Study Site 1
city: Saint Petersburg
country: Russian Federation
facility: Clinical Study Site 2
city: Saint Petersburg
country: Russian Federation
facility: Clinical Study Site 3
city: Saint Petersburg
country: Russian Federation
facility: Clinical Study Site 4
city: Samara
country: Russian Federation
facility: Clinical Study Site
city: Saransk
country: Russian Federation
facility: Clinical Study Site
city: Sochi
country: Russian Federation
facility: Clinical Study Site
city: Tomsk
country: Russian Federation
facility: Clinical Study Site 1
city: Tomsk
country: Russian Federation
facility: Clinical Study Site 2
city: Yekaterinburg
country: Russian Federation
facility: Clinical Study Site
city: Manresa
country: Spain
facility: Clinical Study Site
state: Barcelona
city: Barcelona
country: Spain
facility: Clinical Study Site
city: Pamplona
country: Spain
facility: Clinical Study Site
city: Chang Hua
country: Taiwan
facility: Clinical Study Site
city: Hualien City
country: Taiwan
facility: Clinical Study Site
city: Kaohsiung
country: Taiwan
facility: Clinical Study Site 1
city: Kaohsiung
country: Taiwan
facility: Clinical Study Site 2
city: New Taipei City
country: Taiwan
facility: Clinical Study Site 1
city: New Taipei
country: Taiwan
facility: Clinical Study Site 2
city: Taichung
country: Taiwan
facility: Clinical Study Site 1
city: Taichung
country: Taiwan
facility: Clinical Study Site 2
city: Taipei
country: Taiwan
facility: Clinical Study Site 1
city: Taipei
country: Taiwan
facility: Clinical Study Site 2
city: Taipei
country: Taiwan
facility: Clinical Study Site 3
city: Lop Buri
country: Thailand
facility: Clinical Study Site
state: Muang
city: Hat Yai
country: Thailand
facility: Clinical Study Site
state: Songkhla
city: Bangkok
country: Thailand
facility: Clinical Study Site #1
city: Bangkok
country: Thailand
facility: Clinical Study Site #2
city: Chiang Rai
country: Thailand
facility: Clinical Study Site
city: Khon Kaen
country: Thailand
facility: Clinical Study Site
city: Lampang
country: Thailand
facility: Clinical Study Site
city: Phitsanulok
country: Thailand
facility: Clinical Study Site
city: Ratchathewi
country: Thailand
facility: Clinical Study Site
city: Udon Thani
country: Thailand
facility: Clinical Study Site
city: Adana
country: Turkey
facility: Clinical Study Site 1
city: Adana
country: Turkey
facility: Clinical Study Site 2
city: Ankara
country: Turkey
facility: Clinical Study Site 1
city: Ankara
country: Turkey
facility: Clinical Study Site 2
city: Ankara
country: Turkey
facility: Clinical Study Site 3
city: Ankara
country: Turkey
facility: Clinical Study Site 4
city: Ankara
country: Turkey
facility: Clinical Study Site 5
city: Edirne
country: Turkey
facility: Clinical Study Site
city: Istanbul
country: Turkey
facility: Clinical Study Site 1
city: Istanbul
country: Turkey
facility: Clinical Study Site 2
city: Istanbul
country: Turkey
facility: Clinical Study Site 3
city: Istanbul
country: Turkey
facility: Clinical Study Site 4
city: İzmir
country: Turkey
facility: Clinical Study Site 1
city: İzmir
country: Turkey
facility: Clinical Study Site 2
city: İzmir
country: Turkey
facility: Clinical Study Site 3
city: Samsun
country: Turkey
facility: Clinical Study Site
city: Dnepropetrovsk
country: Ukraine
facility: Clinical Study Site
city: Ivano-Frankivs'k
country: Ukraine
facility: Clinical Study Site
city: Kharkiv
country: Ukraine
facility: Clinical Study Site
city: Kherson
country: Ukraine
facility: Clinical Study Site
city: Kiev
country: Ukraine
facility: Clinical Study Site 1
city: Kiev
country: Ukraine
facility: Clinical Study Site 2
city: Kirovohrad
country: Ukraine
facility: Clinical Study Site
city: Kyiv
country: Ukraine
facility: Clinical Study Site 1
city: Kyiv
country: Ukraine
facility: Clinical Study Site 2
city: Vinnytsia
country: Ukraine
facility: Clinical Study Site
city: Zaporozhye
country: Ukraine
facility: Clinical Study Site
city: Úzhgorod
country: Ukraine
facility: Clinical Study Site
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: Gumus M, Chen CI, Ivanescu C, Kilickap S, Bondarenko I, Ozguroglu M, Gogishvili M, Turk HM, Cicin I, Harnett J, Mastey V, Naumann U, Reaney M, Konidaris G, Sasane M, Brady KJS, Li S, Gullo G, Rietschel P, Sezer A. Patient-reported outcomes with cemiplimab monotherapy for first-line treatment of advanced non-small cell lung cancer with PD-L1 of >/=50%: The EMPOWER-Lung 1 study. Cancer. 2023 Jan 1;129(1):118-129. doi: 10.1002/cncr.34477. Epub 2022 Oct 29.
citation: Sezer A, Kilickap S, Gumus M, Bondarenko I, Ozguroglu M, Gogishvili M, Turk HM, Cicin I, Bentsion D, Gladkov O, Clingan P, Sriuranpong V, Rizvi N, Gao B, Li S, Lee S, McGuire K, Chen CI, Makharadze T, Paydas S, Nechaeva M, Seebach F, Weinreich DM, Yancopoulos GD, Gullo G, Lowy I, Rietschel P. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet. 2021 Feb 13;397(10274):592-604. doi: 10.1016/S0140-6736(21)00228-2.