A Global Study to Assess the Effects of MEDI4736 (Durvalumab) in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer (ATLANTIC)

• ClinicalTrials.gov Identifier: NCT02087423
• Recruitment Status: Active, not recruiting
• First Posted: March 14, 2014
• Results First Posted: January 3, 2018
• Last Update Posted: May 1, 2024
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: March 4, 2014
• First Posted Date: March 14, 2014
• Results First Submitted Date: June 3, 2017
• Results First Posted Date: January 3, 2018
• Last Update Posted Date: May 1, 2024
• Actual Study Start Date: February 25, 2014
• Actual Primary Completion Date: June 3, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 20, 2018)

Objective Response Rate (ORR) [ Time Frame: Responses recorded during initial 12 month treatment period (up to primary analysis DCO) ]

Patients commenced treatment with durvalumab on Day 1 and continued on a Q2W schedule for a maximum of 12 months. Tumor assessments using computed tomography / magnetic resonance imaging were performed every 8 weeks. Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) measurements as given by the Independent Central Review (ICR) were used to derive the primary variable of ORR .

• Original Primary Outcome Measures (submitted: March 13, 2014): Objective response rate (ORR) using Independent Central Review assessments according to RECIST 1.1 [ Time Frame: Screening up to 2 years ]

Current Secondary Outcome Measures (submitted: December 20, 2018)

• Time to Response (TTR) [ Time Frame: Responses recorded during initial 12 month treatment period (up to primary analysis DCO) ]
  TTR (per RECIST 1.1 as assessed by the ICR) is defined as the time from the date of first dose until the date of first documented response (which is subsequently confirmed). TTR was only analyzed for Cohort 2.
• Duration of Response (DoR) [ Time Frame: Time from response to progression, death, or last assessment (up to approximately 2 years 3 months for the primary analysis DCO) ]
  DoR (per RECIST 1.1 as assessed by the ICR) was defined as the time from the date of first documented response (which was subsequently confirmed) until the first date of documented progression or death in the absence of disease progression (ie, date of PFS event or censoring - date of first response + 1). DoR was only analyzed for Cohort 2. Cohort 2: Median DoR was 12.3 months in the PD-L1 high (TC>=25%) group at DCO (Q3 was NR). Of the 7 evaluable patients, the median DoR was not reached in the PD-L1 low/neg group (TC <25%); therefore the DoR "number of participants analyzed" field has been entered as "0" and the DoR results field has been left blank.
• Overall Survival (OS) [ Time Frame: From date of first treatment until final DCO (up to approximately 3 years 8 months) ]
  OS was defined as the time from the date of first dose until death due to any cause (ie, date of death or censoring - date of first dose + 1). Results are reported as median OS, calculated using the Kaplan-Meier methodology.

Original Secondary Outcome Measures (submitted: March 13, 2014)

• Duration of response (DoR) using Independent Central Review assessments according to RECIST 1.1 [ Time Frame: Screening up to 2 years ]
• Progression Free survival (PFS) using Independent Central Review assessments according to RECIST 1.1 [ Time Frame: Screening up to 2 years ]
• Disease control rate (DCR) using Independent Central Review assessments according to RECIST 1.1 [ Time Frame: Screening up to 2 years ]
• Overall Survival (OS, death due to any cause) [ Time Frame: Screening up to 2 years ]
• Deep sustained response (DSR) using Independent Central Review assessments according to RECIST 1.1 [ Time Frame: Screening up to 2 years ]
• Levels of Anti-Drug Antibody (ADA) in patients treated with MEDI4736 [ Time Frame: Day 1 up to 2 years ]
• Levels of tumoural expression of PD-L1 [ Time Frame: Screening up to 2 years ]
• Adverse Events [ Time Frame: Screening up to 2 years ]
• Vital signs (blood pressure and pulse) [ Time Frame: Screening up to 2 years ]
• Electrocardiograms [ Time Frame: Screening up to 2 years ]
• Physical examinations [ Time Frame: Screening up to 2 years ]
• Laboratory findings (clinical chemistry, haematology) [ Time Frame: Screening up to 2 years ]
• Laboratory findings (urinalysis) [ Time Frame: Screening up to 2 years ]
• Concentration of MEDI4736 in blood and non compartmental PK parameters (peak) [ Time Frame: Day 1 up to 2 years ]
• Concentration of MEDI4736 in blood and non compartmental PK parameters (trough) [ Time Frame: Day 1 up to 2 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer

Intervention

Drug: MEDI4736

MEDI4736 (durvalumab) by intravenous infusion every two weeks. Treatment from Day 1 for a maximum of 12 months or study drug withdrawal if this occurs earlier. Patients who achieve CR, PR or SD through the end of the initial 12-month treatment period can restart treatment with MEDI4736 (durvalumab) when they eventually do progress. This retreatment period can continue for as long as the investigator considers to patient to be receiving clinical benefit.

Study Arms

Experimental: MEDI4736

see below

Intervention: Drug: MEDI4736

Publications *

• 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.
• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 4, 2017): 446
• Original Estimated Enrollment (submitted: March 13, 2014): 210
• Estimated Study Completion Date: June 28, 2024
• Actual Primary Completion Date: June 3, 2016 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 130 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, Canada, Czechia, France, Germany, Hungary, Italy, Japan, Korea, Republic of, Philippines, Poland, Singapore, Spain, Taiwan, Thailand, United Kingdom, United States
• Removed Location Countries: Czech Republic, Malaysia

Administrative Information

• NCT Number: NCT02087423
• Other Study ID Numbers: D4191C00003; 2013-005427-16 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Current Responsible Party: AstraZeneca
• Original Responsible Party: Same as current
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Phillip Dennis, MD, PhD; AstraZeneca

• PRS Account: AstraZeneca
• Verification Date: April 2024