Clinical trial NCT05221840: A Global Study to Assess the Effects of Durvalumab With Oleclumab or Durvalumab With Monalizumab Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer
Official title: A Phase III, Double-blind, Placebo-controlled, Randomised, Multicentre, International Study of Durvalumab Plus Oleclumab and Durvalumab Plus Monalizumab in Patients With Locally Advanced (Stage III), Unresectable Non-small Cell Lung Cancer (NSCLC) Who Have Not Progressed Following Definitive, Platinum-Based Concurrent Chemoradiation Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Non-Small Cell Lung Cancer
Keywords: Non-Small Cell Lung Cancer
Locally Advanced NSCLC
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2022-02-03
Enrollment: 999
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 Phase III, randomised, double-blind, multicentre, international study assessing the efficacy and safety of durvalumab (MEDI4736) in combination with oleclumab (MEDI9447) or durvalumab (MEDI4736) with monalizumab (IPH2201) in adults with locally advanced (Stage III), unresectable NSCLC, who have not progressed following platinum-based cCRT.


Eligibility criteria: INCLUSION CRITERIA:

* Participant must be ≥ 18 years at the time of screening.
* Histologically- or cytologically-documented NSCLC and have been treated with concurrent CRT for locally advanced, unresectable (Stage III) disease
* Provision of a tumour tissue sample obtained prior to CRT
* Documented tumour PD-L1 status by central lab
* Documented EGFR and ALK wild-type status (local or central).
* Patients must not have progressed following definitive, platinum based, concurrent chemoradiotherapy
* Participants must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy
* Participants must have received a total dose of radiation of 60 Gy ±10% (54 Gy to 66 Gy) as part of the chemoradiation therapy, to be randomised. Radiation therapy should be administered by intensity modulated RT (preferred) or 3D-conforming technique.
* WHO performance status of 0 or 1 at randomization
* Adequate organ and marrow function

EXCLUSION CRITERIA:

* History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥5 years before the first dose of study intervention and of low potential risk for recurrence, adequately resected non-melanoma skin cancer and curatively treated in situ disease, or adequately treated carcinoma in situ or Ta tumours without evidence of disease.
* Mixed small cell and non-small cell lung cancer histology.
* Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC.
* Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT.
* Any unresolved toxicity CTCAE \>Grade 2 from the prior chemoradiation therapy (excluding alopecia).
* Participants with ≥grade 2 pneumonitis from prior chemoradiation therapy.
* History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, or idiopathic pneumonitis - regardless of time of onset prior to randomisation. Evidence of active non-CRT induced pneumonitis (≥ Grade 2), active pneumonia, active ILD, active or recently treated pleural effusion, or current pulmonary fibrosis - diagnosed in the past 6 months prior to randomization.
* Active or prior documented autoimmune or inflammatory disorders (with exceptions)
* Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.

Primary outcomes:
measure: Progression Free Surival (PFS)
timeFrame: Up to 5 years after first patient randomized.
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to 9 years after first patient randomized
measure: Objective response rate (ORR)
timeFrame: Up to 5 years after first patient randomized
measure: Overall survival (OS) at 24 months
timeFrame: Up to 9 years after first patient randomized
measure: Duration of response (DoR)
timeFrame: Up to 5 years after first patient randomized
measure: Progression free survival (PFS) at 6, 12, 18, and 24 months
timeFrame: From date of randomization until 24 months
measure: Time from randomization to second progression (PFS2)
timeFrame: Up to 5 years after first patient randomized
measure: Time from randomization to first date of distant metastasis or death (TTDM)
timeFrame: Up to 5 years after first patient randomized
measure: Time from randomization to start date of first subsequent therapy (TFST)
timeFrame: Up to 9 years after first patient randomized
measure: Progression free survival (PFS) as assessed by Investigator
timeFrame: Up to 5 years after first patient randomized
measure: IHC analysis of PD-L1 TC expression
timeFrame: Up to 5 years after first patient randomized
measure: Concentration of Durvalumab
timeFrame: From date of randomization until 3 months after date of last IP dose
measure: Anti-drug antibodies (ADAs)
timeFrame: From date of randomization until 3 months after date of last IP dose
measure: Time to deterioration in pulmonary symptoms (TTFCD)
timeFrame: Up to 5 years after last patient randomized
measure: Concentration of Oleclumab
timeFrame: From date of randomization until 3 months after last dose of IP
measure: Concentration of Monalizumab
timeFrame: From date of randomization until 3 months after last dose of IP
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Research Site
state: California
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Stuart
country: United States
facility: Research Site
state: Florida
city: Urbana
country: United States
facility: Research Site
state: Illinois
city: New Albany
country: United States
facility: Research Site
state: Indiana
city: Waterloo
country: United States
facility: Research Site
state: Iowa
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Scarborough
country: United States
facility: Research Site
state: Maine
city: Annapolis
country: United States
facility: Research Site
state: Maryland
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Bethesda
country: United States
facility: Research Site
state: Maryland
city: Grand Rapids
country: United States
facility: Research Site
state: Michigan
city: Duluth
country: United States
facility: Research Site
state: Minnesota
city: Duluth
country: United States
facility: Research Site
state: Minnesota
city: Southaven
country: United States
facility: Research Site
state: Mississippi
city: Billings
country: United States
facility: Research Site
state: Montana
city: Ridgewood
country: United States
facility: Research Site
state: New Jersey
city: Ithaca
country: United States
facility: Research Site
state: New York
city: Middletown
country: United States
facility: Research Site
state: New York
city: Greensboro
country: United States
facility: Research Site
state: North Carolina
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
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state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Independence
country: United States
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state: Ohio
city: Maumee
country: United States
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state: Ohio
city: Portland
country: United States
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state: Oregon
city: Philadelphia
country: United States
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state: Pennsylvania
city: York
country: United States
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state: Pennsylvania
city: Sioux Falls
country: United States
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state: South Dakota
city: Houston
country: United States
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state: Texas
city: Charlottesville
country: United States
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state: Virginia
city: Fairfax
country: United States
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state: Virginia
city: Fredericksburg
country: United States
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state: Virginia
city: Richmond
country: United States
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state: Virginia
city: Richland
country: United States
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state: Washington
city: Spokane
country: United States
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state: Washington
city: Tacoma
country: United States
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state: Washington
city: Milwaukee
country: United States
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state: Wisconsin
city: Box Hill
country: Australia
facility: Research Site
city: East Melbourne
country: Australia
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city: Elizabeth Vale
country: Australia
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city: Gosford
country: Australia
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city: Heidelberg
country: Australia
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city: Kogarah
country: Australia
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city: South Brisbane
country: Australia
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city: St Albans
country: Australia
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city: St. Leonards
country: Australia
facility: Research Site
city: Westmead
country: Australia
facility: Research Site
city: Barretos
country: Brazil
facility: Research Site
city: Belo Horizonte
country: Brazil
facility: Research Site
city: Florianópolis
country: Brazil
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city: Fortaleza
country: Brazil
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city: Jaú
country: Brazil
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city: Natal
country: Brazil
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city: Porto Alegre
country: Brazil
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city: Porto Alegre
country: Brazil
facility: Research Site
city: Recife
country: Brazil
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city: Sao Paulo
country: Brazil
facility: Research Site
city: Uberlândia
country: Brazil
facility: Research Site
city: Vitoria
country: Brazil
facility: Research Site
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Barrie
country: Canada
facility: Research Site
state: Ontario
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: Kingston
country: Canada
facility: Research Site
state: Ontario
city: London
country: Canada
facility: Research Site
state: Ontario
city: Mississauga
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
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state: Ontario
city: Rimouski
country: Canada
facility: Research Site
state: Quebec
city: Anyang
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Jieyang
country: China
facility: Research Site
city: Kunming
country: China
facility: Research Site
city: Linhai
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Nanning
country: China
facility: Research Site
city: Nantong
country: China
facility: Research Site
city: Neijiang
country: China
facility: Research Site
city: Ningbo
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shaoguan
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Zhanjiang
country: China
facility: Research Site
city: Zhengzhou City
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Zhongshan
country: China
facility: Research Site
city: Zhuhai
country: China
facility: Research Site
city: Barranquilla
country: Colombia
facility: Research Site
city: Barranquilla
country: Colombia
facility: Research Site
city: Bogota D.C.
country: Colombia
facility: Research Site
city: Bogotá
country: Colombia
facility: Research Site
city: Medellin
country: Colombia
facility: Research Site
city: Valledupar
country: Colombia
facility: Research Site
city: Avignon Cedex 9
country: France
facility: Research Site
city: Besançon Cedex
country: France
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Clermont-Ferrand
country: France
facility: Research Site
city: Creteil Cedex
country: France
facility: Research Site
city: Lorient cedex
country: France
facility: Research Site
city: Marseille Cedex 20
country: France
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Paris Cedex 5
country: France
facility: Research Site
city: Rennes
country: France
facility: Research Site
city: Rouen
country: France
facility: Research Site
city: Toulouse CEDEX 09
country: France
facility: Research Site
city: Villejuif Cedex
country: France
facility: Research Site
city: Erfurt
country: Germany
facility: Research Site
city: Erlangen
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Esslingen
country: Germany
facility: Research Site
city: Georgsmarienhuette
country: Germany
facility: Research Site
city: Guetersloh
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Oldenburg
country: Germany
facility: Research Site
city: Würzburg
country: Germany
facility: Research Site
city: Brescia
country: Italy
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Lucca
country: Italy
facility: Research Site
city: Meldola
country: Italy
facility: Research Site
city: Orbassano
country: Italy
facility: Research Site
city: Parma
country: Italy
facility: Research Site
city: Pavia
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Himeji-shi
country: Japan
facility: Research Site
city: Hiroshima-shi
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Kurume-shi
country: Japan
facility: Research Site
city: Natori-shi
country: Japan
facility: Research Site
city: Niigata-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Sendai-shi
country: Japan
facility: Research Site
city: Tokushima-shi
country: Japan
facility: Research Site
city: Toon-shi
country: Japan
facility: Research Site
city: Wakayama-shi
country: Japan
facility: Research Site
city: Changwon-si
country: Korea, Republic of
facility: Research Site
city: Cheongju-si
country: Korea, Republic of
facility: Research Site
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon-si
country: Korea, Republic of
facility: Research Site
city: Suwon
country: Korea, Republic of
facility: Research Site
city: Arequipa
country: Peru
facility: Research Site
city: Concepción
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
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city: Lima
country: Peru
facility: Research Site
city: Lima
country: Peru
facility: Research Site
city: Trujillo
country: Peru
facility: Research Site
city: Brzozów
country: Poland
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Gdańsk
country: Poland
facility: Research Site
city: Koszalin
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Siedlce
country: Poland
facility: Research Site
city: Tomaszów Mazowiecki
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Alcabideche
country: Portugal
facility: Research Site
city: Coimbra
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Loures
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Yekaterinburg
country: Russian Federation
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Granada
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Santiago de Compostela
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Hsinchu
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taipei 112
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan City
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Hat Yai
country: Thailand
facility: Research Site
city: Khon Kaen
country: Thailand
facility: Research Site
city: Khon Kaen
country: Thailand
facility: Research Site
city: Lampang
country: Thailand
facility: Research Site
city: Muang
country: Thailand
facility: Research Site
city: Muang
country: Thailand
facility: Research Site
city: Mueang
country: Thailand
facility: Research Site
city: Naimuang
country: Thailand
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Diyarbakir
country: Turkey
facility: Research Site
city: Goztepe Istanbul
country: Turkey
facility: Research Site
city: Karsiyaka
country: Turkey
facility: Research Site
city: Chernihiv
country: Ukraine
facility: Research Site
city: Kharkiv Region
country: Ukraine
facility: Research Site
city: Kropyvnytskyi
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Uzhgorod
country: Ukraine
facility: Research Site
city: Zaporizhzhia
country: Ukraine
facility: Research Site
city: Belfast
country: United Kingdom
facility: Research Site
city: Bristol
country: United Kingdom
facility: Research Site
city: Dundee
country: United Kingdom
facility: Research Site
city: Edinburgh
country: United Kingdom
facility: Research Site
city: Hampshire
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Middlesborough
country: United Kingdom
facility: Research Site
city: Poole
country: United Kingdom
facility: Research Site
city: Rhyl
country: United Kingdom
facility: Research Site
city: Torquay
country: United Kingdom
facility: Research Site
city: Truro
country: United Kingdom
facility: Research Site
city: Wolverhampton
country: United Kingdom
facility: Research Site
city: Hai Phong
country: Vietnam
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh city
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
name: Fabrice Barlesi, MD
role: PRINCIPAL_INVESTIGATOR
References: