Description:
This is a randomized, open-label, multi-center, global, Phase III study to determine the
efficacy and safety of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy
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 locally advanced
or metastatic NSCLC
Phase III Open Label First Line Therapy Study of MEDI 4736 With or Without <span class="go-doc-concept go-doc-intervention">Tremelimumab</span> Versus SOC in Non Small-Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span> (<span class="go-doc-concept go-doc-disease">NSCLC</span>).
Title
Brief Title: Phase III Open Label First Line Therapy Study of MEDI 4736 With or Without Tremelimumab Versus SOC in Non Small-Cell Lung Cancer (NSCLC).
Official Title: A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 in Combination With Tremelimumab Therapy or MEDI4736 Monotherapy 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
NCT ID: NCT02453282
ORG ID: D419AC00001
Trial Conditions
Non-Small-Cell Lung Carcinoma (NSCLC)
Trial Interventions
Drug |
Synonyms |
Arms |
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 |
Trial Purpose
This is a randomized, open-label, multi-center, global, Phase III study to determine the
efficacy and safety of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy
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 1:1:1 ratio to receive treatment with MEDI4736 +
tremelimumab combination therapy, MEDI4736 monotherapy, or Standard of Care (SoC) therapy.
The primary objective of this study is to assess the efficacy of combination or monotherapy
treatment compared with SoC in terms of Progression Free Survival (PFS) in patients.
Trial Arms
Name |
Type |
Description |
Interventions |
Monotherapy |
Experimental |
PD-L1 monoclonal Antibody monotherapy. |
|
Combination Therapy |
Experimental |
PD-L1+Tremelimumab combination therapy |
|
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
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 or not otherwise specified (NSCLC
NOS)
- Brain metastases or spinal cord compression unless asymptomatic, treated and stable
(not requiring steroids)
- Prior exposure to Immunomodulatory therapy (IMT), including, but not limited to,
other anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), anti-programmed cell
death1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti PD-L2 antibodies,
excluding therapeutic anticancer vaccines
- Active or prior documented inflammatory bowel disease (eg, Crohn's disease,
ulcerative colitis)
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both
Primary Outcome Measures
The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of progression-free survival (PFS) in patients with NSCLC
Secondary Outcome Measures
The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of progression-free survival (PFS)
The efficacy of MEDI4736 monotherapy compared to SoC in terms of progression free survival (PFS)
Health related quality of life (HRQoL) in patients treated with MEDI4736 + tremelimumab or MEDI4736 compared to SoC using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 items (EORTC QLQ-C30)
The pharmacokinetics (PK) of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy
The immunogenicity of MEDI4736 and tremelimumab
The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Objective Response Rate (ORR)
The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Duration of Response (DoR)
The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of alive and progression free at 12 months (APF12)
The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of time from randomization to second progression (PFS2)
The efficacy of MEDI4736 + tremelimumab combination therapy compared to SoC in terms of Overall Survival (OS)
The efficacy of MEDI4736 monotherapy compared to SoC in terms of Objective Response Rate (ORR)
The efficacy of MEDI4736 monotherapy compared to SoC in terms of time from randomization to second progression (PFS2)
The efficacy of MEDI4736 monotherapy compared to SoC in terms of Overall Survival (OS)
Disease-related symptoms and HRQoL in patients treated with MEDI4736 + tremelimumab or MEDI4736 compared to SoC using the European Organization for Research and Treatment of Cancer Quality of LifeQuestionnaire - Lung Cancer 13 items (EORTC QLQ-LC13).
Trial Keywords
NSCLC, PD-L1, MEDI4736, Tremelimumab, PFS