Description:
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.
Title
- Brief Title: Study of Durvalumab With Tremelimumab Versus SoC as 1st Line Therapy in Metastatic Non Small-Cell Lung Cancer (NSCLC) (NEPTUNE).
- Official 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)
Clinical Trial IDs
- ORG STUDY ID:
D419AC00003
- NCT ID:
NCT02542293
Conditions
- Non Small Cell Lung Carcinoma NSCLC
Interventions
| Drug | Synonyms | Arms |
|---|
| Durvalumab +Tremelimumab | | Combination Therapy |
| Paclitaxel + carboplatin | Platinum based Standard of Care Chemotherapy | Standard of Care |
| Gemcitabine + cisplatin | Platinum based Standard of Care Chemotherapy | Standard of Care |
| Gemcitabine + carboplatin | Platinum based Standard of Care Chemotherapy | Standard of Care |
| Pemetrexed + cisplatin | Platinum based Standard of Care Chemotherapy | Standard of Care |
| Pemetrexed + carboplatin | Platinum based Standard of Care Chemotherapy | Standard of Care |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Combination Therapy | Experimental | Durvalumab (PD-L1 monoclonal antibody) + Tremelimumab (monoclonal antibody directed against CTLA-4) | |
| Standard of Care | Active Comparator | Standard of Care chemotherapy treatment | - Paclitaxel + carboplatin
- Gemcitabine + cisplatin
- Gemcitabine + carboplatin
- Pemetrexed + cisplatin
- Pemetrexed + carboplatin
|
Eligibility Criteria
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)
| Maximum Eligible Age: | 130 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | 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 |
| Safety Issue: | |
| Description: | Assess the Overall Survival |
Secondary Outcome Measures
| Measure: | 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 |
| Safety Issue: | |
| Description: | Additional bTMB defined populations, PD-L1 negative NSCLC, all patients with NSCLC |
| Measure: | 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 |
| Safety Issue: | |
| Description: | bTMB defined populations, PD-L1 negative NSCLC, all patients with NSCLC |
| Measure: | 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 |
| Safety Issue: | |
| Description: | bTMB defined populations, PD-L1 negative NSCLC, all patients with NSCLC |
| Measure: | 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 |
| Safety Issue: | |
| Description: | bTMB defined populations, PD-L1 negative NSCLC, all patients with NSCLC |
| Measure: | 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 |
| Safety Issue: | |
| Description: | bTMB defined populations, PD-L1 negative NSCLC, all patients with NSCLC |
| Measure: | 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 |
| Safety Issue: | |
| Description: | bTMB defined populations, PD-L1 negative NSCLC, all patients with NSCLC |
| Measure: | 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 |
| Safety Issue: | |
| Description: | bTMB defined populations, PD-L1 negative NSCLC, all patients with NSCLC |
| Measure: | 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 |
| Safety Issue: | |
| Description: | bTMB defined populations, PD-L1 negative NSCLC, all patients with NSCLC |
| Measure: | 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' |
| Safety Issue: | |
| Description: | bTMB defined populations, PD-L1 negative NSCLC, all patients with NSCLC |
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Safety Issue: | |
| Description: | tTMB defined populations |
| Measure: | 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 |
| Safety Issue: | |
| Description: | tTMB defined populations |
| Measure: | 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 |
| Safety Issue: | |
| Description: | tTMB defined populations |
| Measure: | To assess the pharmacokinetics (PK) of MEDI4736 + tremelimumab combination therapy |
| Time Frame: | Up to 4 years 6 months after first patient randomized |
| Safety Issue: | |
| Description: | Serum concentration of MEDI4736 and tremelimumab |
| Measure: | To investigate the immunogenicity of MEDI4736 and tremelimumab |
| Time Frame: | Up to 4 years 6 months after first patient randomized |
| Safety Issue: | |
| Description: | Detection of the presence of anti-drug antibodies for MEDI4736 and tremelimumab |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | AstraZeneca |
Trial Keywords
- NSCLC
- PDL1
- TMB
- MEDI4736
- Durvalumab
- Tremelimumab
- OS
Last Updated
July 7, 2021
