Study of Durvalumab with Tremelimumab Versus standard of care chemotherapy in lung cancer (NEPTUNE Study).

• Register: EUCTR
• Last refreshed on: 6 October 2020
• Main ID: EUCTR2015-002197-21-SE
• Date of registration: 23/11/2015
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: Study of Durvalumab with Tremelimumab Versus standard of care chemotherapy in lung cancer (NEPTUNE Study).
• Scientific title: 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) (NEPTUNE). - NEPTUNE
• Date of first enrolment: 27/11/2015
• Target sample size: 1330
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002197-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: Platinum based doublet chemotherapy Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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 Arab Emirates, United Kingdom, United States

Contacts

• Name: Information Center
• Affiliation: AstraZeneca AB

• Name: Information Center
• Affiliation: AstraZeneca AB

Key inclusion & exclusion criteria

Inclusion criteria:
1. Aged at least 18 years.

2. Documented evidence of Stage IV NSCLC.

3. No activating EGFR mutation or ALK rearrangement.

4. No prior chemotherapy or any other systemic therapy for advanced or metastatic NSCLC.

5. Confirmed tumor PD-L1 status.

6. World Health Organization (WHO) Performance Status of 0 or 1.

7. No Prior exposure to IMT, including, but not limited to, other antiCTLA4, antiPD1, anti PDL1,or anti PDL2 antibodies, excluding therapeutic anticancer vaccines
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 480
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 480

Exclusion criteria:
1. Mixed small cell lung cancer and NSCLC histology, sarcomatoid variant
2. 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.
3. Active or prior documented autoimmune or inflammatory disorders (e.g., Crohn's disease, ulcerative colitis)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) in treatment naive patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild type tumour pathology.
MedDRA version: 20.0 Level: LLT Classification code 10025055 Term: Lung cancer non-small cell stage IV System Organ Class: 100000004864

Intervention(s)

Product Name: MEDI4736
Product Code: MEDI4736
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: durvalumab
CAS Number: 1428935-60-7
Current Sponsor code: MEDI4736
Other descriptive name: MEDI4736
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Product Name: Tremelimumab
Product Code: MEDI1123
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Tremelimumab
CAS Number: 745013-19-6
Current Sponsor code: MEDI1123
Other descriptive name: MEDI1123
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Trade Name: Paclitaxel
Product Name: Paclitaxel
Product Code: NA
Pharmaceutical Form: Concentrate for solution for infusion
CAS Number: 33069-62-4
Other descriptive name: PACLITAXEL
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 6-

Trade Name: Carboplatin
Product Name: Carboplatin
Product Code: NA
Pharmaceutical Form: Solution for infusion
Current Sponsor code: 41575-94-4
Other descriptive name: CARBOPLATIN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Gemcitabine
Product Name: Gemcitabine
Product Code: NA
Pharmaceutical Form: Powder for solution for infusion
CAS Number: 95058-81-4
Other descriptive name: GEMCITABINE
Concentration unit: g gram(s)
Concentration type: range
Concentration number: 0.2-2

Trade Name: Cisplatin
Product Name: Cisplatin
Product Code: NA
Pharmaceutical Form: Concentrate for solution for infusion
Other descriptive name: CISPLATIN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Trade Name: ALIMTA (Pemetrexed)
Product Name: P

Primary Outcome(s)

Main Objective: To assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of OS in patients with bTMB = 20mut/Mb.

Secondary Objective: -To assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of OS.
-To further assess the efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of PFS, ORR, DoR, OS12, OS18, OS24, APF12, and PFS2.
-To assess efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of ORR, PFS and OS in further PD-L1 defined populations.
-To further assess efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of ORR, PFS and OS.
-To assess the pharmacokinetics (PK) of MEDI4736 + tremelimumab combination therapy.
-To investigate the immunogenicity of MEDI4736 and tremelimumab.

Timepoint(s) of evaluation of this end point: From baseline to until death due to any cause

Primary end point(s): To determine the efficacy of MEDI4736 + tremelimumab combination therapy versus SoC in terms of OS in patients with high bTMB, defined as bTMB =20mut/Mb.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: - For OS - from baseline to until death due to any cause.

- For PFS, ORR, DOR, PFS2 - at baseline, then every 6 weeks for the first 48 weeks relative to the date of randomization, and then every 8 weeks until progression.

- PK (durvalumab) 12 and 24 weeks from randomization.

- PK (Tremelimumab) 12 weeks from randomization.

- ADAs 12 and 24 weeks from randomization.

Secondary end point(s): - OS in patients with: bTMB = 16mut/Mb NSCLC, bTMB = 12 mut/Mb NSCLC, PD-L1-negative NSCLC, all patients with NSCLC, bTMB < 20 mut/Mb NSCLC, bTMB non-evaluable population.
- PFS, ORR, DoR and APF12 using Investigator assessments according to RECIST 1.1 in patients with: bTMB = 20mut/Mb NSCLC, bTMB = 16mut/Mb NSCLC, bTMB = 12mut/Mb NSCLC, PD-L1 negative NSCLC, all patients with NSCLC; PFS2 using local standard clinical practice, OS12, OS18 and OS24 in patients with: bTMB = 20mut/Mb NSCLC, bTMB = 16mut/Mb NSCLC, bTMB = 12mut/Mb NSCLC, PD-L1 negative NSCLC, all patients with NSCLC.
- OS in patients with PD-L1 TC = 25% and PD-L1 TC = 50%.
- PFS and ORR using Investigator assessments according to RECIST 1.1 in patients with PD-L1 TC = 25% and PD-L1 TC = 50%.
- OS in patients in analysis sets defined by tTMB cutoffs.
- PFS and ORR using Investigator assessments according to RECIST 1.1 in patients in analysis sets defined by tTMB cutoffs.
- Concentration of MEDI4736 and tremelimumab in blood and non-compartmental PK parameters, such as peak concentration and trough (as data allow; sparse sampling).
- Presence of anti-drug antibodies (ADAs) for MEDI4736 and tremelimumab (confirmatory results: positive and negative; titers).

Secondary ID(s)

2015-002197-21-BG

D419AC00003

NCT02542293

Source(s) of Monetary Support

AstraZeneca AB

Ethics review

Status: Approved
Approval date: 28/10/2015
Contact: