Clinical trial NCT02087423: A Global Study to Assess the Effects of MEDI4736 (Durvalumab) in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer
Official title: A Phase II,Non-comparative,Open Label, Multi-centre, International Study of MEDI4736, in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer (Stage IIIB-IV) Who Have Received at Least 2 Prior Systemic Treatment Regimens Including 1 Platinum-based Chemotherapy Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: Locally advanced, metastatic, Non-Small Cell Lung Cancer, MEDI4736, Durvalumab, PD-L1
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2014-03-14
Enrollment: 446
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A study to assess the Effects of MEDI4736 (Durvalumab) in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer in terms of efficacy, safety and tolerability

Detailed description: This study is designed to investigate the efficacy, safety, tolerability of a new drug, MEDI4736 (Durvalumab), in patients with Locally Advanced or Metastatic Non Small Cell Lung Cancer. MEDI4736 will be investigated in patients who have received at least two prior treatment regimens including one platinum-based chemotherapy

Eligibility criteria: Inclusion Criteria:

* Aged at least 18 years.
* Documented evidence of NSCLC (stage IIIB/IV disease)
* Disease progression or recurrence after both a platinum-based chemotherapy and at least 1 additional regimen for treatment of NSCLC
* World Health Organisation (WHO) Performance Status of 0 or 1
* Estimated life expectancy of more than 12 weeks
* Patient's tumour sample must be PD-L1 positive (≥25%of tumour cells with membrane staining (Cohort 1 and 2) or PD-L1 positive with ≥90% of tumour cells with membrane staining (Cohort 3))

Exclusion Criteria:

* Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
* Brain metastases or spinal cord compression or unless asymptomatic, treated and stable (not requiring steroids).
* Active or prior autoimmune disease or history of immunodeficiency
* Evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses or active infections including hepatitis B, C and HIV.
* Evidence of uncontrolled illness such as symptomatic congestive heart failure, uncontrolled hypertension or unstable angina pectoris.
* Any unresolved toxicity CTCAE \>Grade 2 from previous anti-cancer therapy.
* Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \>Grade 1
* Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Responses recorded during initial 12 month treatment period (up to primary analysis DCO)
Secondary outcomes:
measure: Time to Response (TTR)
timeFrame: Responses recorded during initial 12 month treatment period (up to primary analysis DCO)
measure: Duration of Response (DoR)
timeFrame: Time from response to progression, death, or last assessment (up to approximately 2 years 3 months for the primary analysis DCO)
measure: Overall Survival (OS)
timeFrame: From date of first treatment until final DCO (up to approximately 3 years 8 months)
Other outcomes:
Locations:
city: Goodyear
country: United States
facility: Research Site
state: Arizona
city: Santa Rosa
country: United States
facility: Research Site
state: California
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Port Saint Lucie
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Lawrenceville
country: United States
facility: Research Site
state: Georgia
city: Waterloo
country: United States
facility: Research Site
state: Iowa
city: Topeka
country: United States
facility: Research Site
state: Kansas
city: Bethesda
country: United States
facility: Research Site
state: Maryland
city: Burlington
country: United States
facility: Research Site
state: Massachusetts
city: Worcester
country: United States
facility: Research Site
state: Massachusetts
city: Saint Louis Park
country: United States
facility: Research Site
state: Minnesota
city: Bronx
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Huntersville
country: United States
facility: Research Site
state: North Carolina
city: Bismarck
country: United States
facility: Research Site
state: North Dakota
city: Fargo
country: United States
facility: Research Site
state: North Dakota
city: Blue Ash
country: United States
facility: Research Site
state: Ohio
city: Canton
country: United States
facility: Research Site
state: Ohio
city: Middletown
country: United States
facility: Research Site
state: Ohio
city: Chattanooga
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Fort Worth
country: United States
facility: Research Site
state: Texas
city: Spokane
country: United States
facility: Research Site
state: Washington
city: Wenatchee
country: United States
facility: Research Site
state: Washington
city: Wien
country: Austria
facility: Research Site
city: Brussel
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: Gilly
country: Belgium
facility: Research Site
city: Kortrijk
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Liège
country: Belgium
facility: Research Site
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: London
country: Canada
facility: Research Site
state: Ontario
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Regina
country: Canada
facility: Research Site
state: Saskatchewan
city: Brno
country: Czechia
facility: Research Site
city: Praha 5
country: Czechia
facility: Research Site
city: Praha 8
country: Czechia
facility: Research Site
city: Praha
country: Czechia
facility: Research Site
city: Bordeaux Cedex
country: France
facility: Research Site
city: Brest Cedex
country: France
facility: Research Site
city: Creteil
country: France
facility: Research Site
city: Dijon
country: France
facility: Research Site
city: Le Mans Cedex 02
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Pessac
country: France
facility: Research Site
city: Rennes Cedex 09
country: France
facility: Research Site
city: Saint Herblain Cedex
country: France
facility: Research Site
city: Toulouse Cedex 9
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Borstel
country: Germany
facility: Research Site
city: Dortmund
country: Germany
facility: Research Site
city: Frankfurt am Main
country: Germany
facility: Research Site
city: Freiburg
country: Germany
facility: Research Site
city: Grosshansdorf
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Győr
country: Hungary
facility: Research Site
city: Szolnok
country: Hungary
facility: Research Site
city: Tatabánya
country: Hungary
facility: Research Site
city: Törökbálint
country: Hungary
facility: Research Site
city: Candiolo
country: Italy
facility: Research Site
city: Catania
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Monza
country: Italy
facility: Research Site
city: Orbassano
country: Italy
facility: Research Site
city: Perugia
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Rozzano
country: Italy
facility: Research Site
city: Akashi-shi
country: Japan
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Habikino-shi
country: Japan
facility: Research Site
city: Hidaka-shi
country: Japan
facility: Research Site
city: Hirakata-shi
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Kitaadachi-gun
country: Japan
facility: Research Site
city: Kobe-shi
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Kurume-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Natori-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Osakasayama
country: Japan
facility: Research Site
city: Sakai-shi
country: Japan
facility: Research Site
city: Sendai-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Sunto-gun
country: Japan
facility: Research Site
city: Ube-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Hwasun-gun
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: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Cebu City
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Gdańsk
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Gerona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Hat Yai
country: Thailand
facility: Research Site
city: Muang
country: Thailand
facility: Research Site
city: Edinburgh
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Stoke-on-Trent
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Phillip Dennis, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Gavrilov S, Zhudenkov K, Helmlinger G, Dunyak J, Peskov K, Aksenov S. Longitudinal Tumor Size and Neutrophil-to-Lymphocyte Ratio Are Prognostic Biomarkers for Overall Survival in Patients With Advanced Non-Small Cell Lung Cancer Treated With Durvalumab. CPT Pharmacometrics Syst Pharmacol. 2021 Jan;10(1):67-74. doi: 10.1002/psp4.12578. Epub 2020 Dec 21.
citation: Zhang Q, Luo J, Wu S, Si H, Gao C, Xu W, Abdullah SE, Higgs BW, Dennis PA, van der Heijden MS, Segal NH, Chaft JE, Hembrough T, Barrett JC, Hellmann MD. Prognostic and Predictive Impact of Circulating Tumor DNA in Patients with Advanced Cancers Treated with Immune Checkpoint Blockade. Cancer Discov. 2020 Dec;10(12):1842-1853. doi: 10.1158/2159-8290.CD-20-0047. Epub 2020 Aug 14.
citation: Garassino MC, Cho BC, Kim JH, Mazieres J, Vansteenkiste J, Lena H, Jaime JC, Gray JE, Powderly J, Chouaid C, Bidoli P, Wheatley-Price P, Park K, Soo RA, Poole L, Wadsworth C, Dennis PA, Rizvi NA. Final overall survival and safety update for durvalumab in third- or later-line advanced NSCLC: The phase II ATLANTIC study. Lung Cancer. 2020 Sep;147:137-142. doi: 10.1016/j.lungcan.2020.06.032. Epub 2020 Jun 30.
citation: Ouwens MJNM, Mukhopadhyay P, Zhang Y, Huang M, Latimer N, Briggs A. Estimating Lifetime Benefits Associated with Immuno-Oncology Therapies: Challenges and Approaches for Overall Survival Extrapolations. Pharmacoeconomics. 2019 Sep;37(9):1129-1138. doi: 10.1007/s40273-019-00806-4.
citation: Garassino MC, Cho BC, Kim JH, Mazieres J, Vansteenkiste J, Lena H, Corral Jaime J, Gray JE, Powderly J, Chouaid C, Bidoli P, Wheatley-Price P, Park K, Soo RA, Huang Y, Wadsworth C, Dennis PA, Rizvi NA; ATLANTIC Investigators. Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study. Lancet Oncol. 2018 Apr;19(4):521-536. doi: 10.1016/S1470-2045(18)30144-X. Epub 2018 Mar 12.