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Study of Durvalumab With Tremelimumab Versus SoC as 1st Line Therapy in Metastatic Non Small-Cell Lung Cancer (NSCLC) (NEPTUNE). (NEPTUNE)

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ClinicalTrials.gov Identifier: NCT02542293
Recruitment Status : Active, not recruiting
First Posted : September 7, 2015
Last Update Posted : June 10, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE August 26, 2015
First Posted Date  ICMJE September 7, 2015
Last Update Posted Date June 10, 2019
Actual Study Start Date  ICMJE November 3, 2015
Estimated Primary Completion Date August 22, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 6, 2019)
To assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to Standard of Care (SoC) in terms of Overall Survival (OS) in patients with bTMB ≥ 20mut/Mb [ Time Frame: Up to 4 years 6 months after first patient randomized ]
Assess the Overall Survival
Original Primary Outcome Measures  ICMJE
 (submitted: September 3, 2015)
To assess the efficacy of MEDI4736 + tremelimumab combintion therapy compared to Standard of Care (SoC) in terms of Overall Survival (OS) in patients with Non-small-cell lung cancer (NSCLC) [ Time Frame: Up to 4 years after first patient randomized ]
Assess the Overall Survival
Change History Complete list of historical versions of study NCT02542293 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 6, 2019)
  • To assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of OS [ Time Frame: Up to 4 years 6 months after first patient randomized ]
    Additional bTMB defined populations, PD-L1 negative NSCLC, all patients with NSCLC
  • To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Progression-free survival (PFS) [ Time Frame: Up to 4 years 6 months after first patient randomized ]
    bTMB defined populations, PD-L1 negative NSCLC, all patients with NSCLC
  • To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Objective response rate (ORR) [ Time Frame: Up to 4 years 6 months after first patient randomized ]
    bTMB defined populations, PD-L1 negative NSCLC, all patients with NSCLC
  • To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Duration of response (DoR) [ Time Frame: Up to 4 years 6 months after first patient randomized ]
    bTMB defined populations, PD-L1 negative NSCLC, all patients with NSCLC
  • To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Proportion of patients alive at 12 months (OS12) [ Time Frame: Up to 4 years 6 months after first patient randomized ]
    bTMB defined populations, PD-L1 negative NSCLC, all patients with NSCLC
  • To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of OS18 [ Time Frame: Up to 4 years 6 months after first patient randomized ]
    bTMB defined populations, PD-L1 negative NSCLC, all patients with NSCLC
  • To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of OS24 [ Time Frame: Up to 4 years 6 months after first patient randomized ]
    bTMB defined populations, PD-L1 negative NSCLC, all patients with NSCLC
  • To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Proportion of patients alive and progression free at 12 months (APF12) [ Time Frame: Up to 4 years 6 months after first patient randomized ]
    bTMB defined populations, PD-L1 negative NSCLC, all patients with NSCLC
  • To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Progression-free survival after subsequent anticancer therapy (PFS2) [ Time Frame: Up to 4 years 6 months after first patient randomized' ]
    bTMB defined populations, PD-L1 negative NSCLC, all patients with NSCLC
  • To assess efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of ORR in further PD-L1 defined populations [ Time Frame: Up to 4 years 6 months after first patient randomized ]
  • To assess efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of PFS in further PD-L1 defined populations [ Time Frame: Up to 4 years 6 months after first patient randomized ]
  • To assess efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of OS in further PD-L1 defined populations [ Time Frame: Up to 4 years 6 months after first patient randomized ]
  • To further assess efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of ORR [ Time Frame: Up to 4 years 6 months after first patient randomized ]
    tTMB defined populations
  • To further assess efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of PFS [ Time Frame: Up to 4 years 6 months after first patient randomized ]
    tTMB defined populations
  • To further assess efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of OS [ Time Frame: Up to 4 years 6 months after first patient randomized ]
    tTMB defined populations
  • To assess the pharmacokinetics (PK) of MEDI4736 + tremelimumab combination therapy [ Time Frame: Up to 4 years 6 months after first patient randomized ]
    Serum concentration of MEDI4736 and tremelimumab
  • To investigate the immunogenicity of MEDI4736 and tremelimumab [ Time Frame: Up to 4 years 6 months after first patient randomized ]
    Detection of the presence of anti-drug antibodies for MEDI4736 and tremelimumab
Original Secondary Outcome Measures  ICMJE
 (submitted: September 3, 2015)
  • To assess the efficacy of MEDI4736 +tremelimumab combination therapy compared to SoC in terms of OS in patients with PD-L1-negative NSCLC [ Time Frame: Up to 4 years after first patient randomized ]
  • To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Progression-free survival (PFS). [ Time Frame: Up to 4 years after first patient randomized ]
  • To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Objective response rate (ORR). [ Time Frame: Up to 4 years after first patient randomized ]
  • To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Duration of response (DoR). [ Time Frame: Up to 4 years after first patient randomized ]
  • To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Proportion of patients alive at 18 months (OS18). [ Time Frame: Up to 4 years after first patient randomized ]
  • To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Proportion of patients alive and progression free at 12 months (APF12). [ Time Frame: Up to 4 years after first patient randomized ]
  • To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Progression-free survival after subsequent anticancer therapy (PFS2). [ Time Frame: Up to 4 years after first patient randomized' ]
  • To assess the PK paramenters of MEDI4736 + tremelimumab combination therapy by measuring the concentration in blood and non compartmental PK parameters such as peak concentration and trough [ Time Frame: Up to 4 years after first patient randomized ]
  • To investigate the immunogenicity of MEDI4736 and tremelimumab by measuring the presence of Anti-drug Antibodies (confirmatory results: positive and negative; titers) [ Time Frame: Up to 4 years after first patient randomized ]
Current Other Pre-specified Outcome Measures
 (submitted: June 6, 2019)
To assess the number of Treatment-Related Adverse Events as assessed by CTCAE v4.03 for patients receiving durvalumab + tremelimumab combination therapy or SoC. [ Time Frame: Up to 4 years 6 months after first patient randomized ]
Original Other Pre-specified Outcome Measures
 (submitted: September 3, 2015)
To assess the number of Treatment-Related Adverse Events as assessed by CTCAE v4.03 for patients receiving MEDI4736 + tremelimumab combination therapy or SoC. [ Time Frame: Up to 4 years after first patient randomized ]
 
Descriptive Information
Brief Title  ICMJE Study of Durvalumab With Tremelimumab Versus SoC as 1st Line Therapy in Metastatic Non Small-Cell Lung Cancer (NSCLC) (NEPTUNE).
Official Title  ICMJE A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 in Combination With Tremelimumab Therapy Versus Standard of Care Platinum-Based Chemotherapy in First-Line Treatment of Patients With Advanced or Metastatic Non Small-Cell Lung Cancer (NSCLC)
Brief Summary This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of durvalumab + tremelimumab combination therapy versus platinum-based SoC chemotherapy in the first-line treatment of patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type advanced or metastatic NSCLC.
Detailed Description Patients will be randomized in a 1:1 to receive treatment with durvalumab + tremelimumab combination therapy or SoC therapy. The primary objective of this study is to assess the efficacy of combination treatment compared with SoC in terms of Overall Survival (OS) in patients.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non Small Cell Lung Carcinoma NSCLC
Intervention  ICMJE
  • Biological: Durvalumab +Tremelimumab
  • Drug: Paclitaxel + carboplatin
    Chemotherapy Agents
    Other Name: Platinum based Standard of Care Chemotherapy
  • Drug: Gemcitabine + cisplatin
    Chemotherapy Agents
    Other Name: Platinum based Standard of Care Chemotherapy
  • Drug: Gemcitabine + carboplatin
    Chemotherapy Agents
    Other Name: Platinum based Standard of Care Chemotherapy
  • Drug: Pemetrexed + cisplatin
    Chemotherapy Agent
    Other Name: Platinum based Standard of Care Chemotherapy
  • Drug: Pemetrexed + carboplatin
    Chemotherapy Agent
    Other Name: Platinum based Standard of Care Chemotherapy
Study Arms  ICMJE
  • Experimental: Combination Therapy
    Durvalumab (PD-L1 monoclonal antibody) + Tremelimumab (monoclonal antibody directed against CTLA-4)
    Intervention: Biological: Durvalumab +Tremelimumab
  • Active Comparator: Standard of Care
    Standard of Care chemotherapy treatment
    Interventions:
    • Drug: Paclitaxel + carboplatin
    • Drug: Gemcitabine + cisplatin
    • Drug: Gemcitabine + carboplatin
    • Drug: Pemetrexed + cisplatin
    • Drug: Pemetrexed + carboplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: June 6, 2019)
955
Original Estimated Enrollment  ICMJE
 (submitted: September 3, 2015)
800
Estimated Study Completion Date  ICMJE August 22, 2019
Estimated Primary Completion Date August 22, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

For inclusion in the study, patients should fulfill the following criteria:

  • Aged at least 18 years
  • Documented evidence of Stage IV NSCLC
  • No activating EGFR mutation or ALK rearrangement
  • No prior chemotherapy or any other systemic therapy for recurrent/metastatic NSCLC
  • World Health Organization (WHO) Performance Status of 0 or 1
  • No Prior exposure to Immune Mediated Therapy (IMT), including, but not limited to, other antiCTLA4, antiPD1, anti PDL1,or antiPDL2 antibodies, excluding therapeutic anticancer vaccines

Exclusion Criteria:

Patients should not enter the study if any of the following exclusion criteria are fulfilled:

  • Mixed small cell lung cancer and NSCLC histology, sarcomatoid variant
  • Brain metastases or spinal cord compression unless the patient is stable (asymptomatic; no evidence of new or emerging brain metastases) and off steroids for at least 14 days prior to start of study treatment.
  • Active or prior documented autoimmune or inflammatory disorders (e.g., Crohn's disease, ulcerative colitis)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Brazil,   Bulgaria,   Chile,   China,   Denmark,   Finland,   Greece,   Hong Kong,   India,   Israel,   Japan,   Korea, Republic of,   Malaysia,   Mexico,   Peru,   Philippines,   Poland,   Portugal,   Qatar,   Romania,   Russian Federation,   Saudi Arabia,   Singapore,   Sweden,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries United Arab Emirates
 
Administrative Information
NCT Number  ICMJE NCT02542293
Other Study ID Numbers  ICMJE D419AC00003
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Gilberto de Castro Faculdade de Medicina da Universidade de São Paulo
PRS Account AstraZeneca
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP