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).
概览
- 阶段
- 3 期
- 干预措施
- Pemetrexed + carboplatin
- 疾病 / 适应症
- Non Small Cell Lung Carcinoma NSCLC
- 发起方
- AstraZeneca
- 入组人数
- 953
- 试验地点
- 211
- 主要终点
- Overall Survival (OS); Global Cohort: Blood Tumor Mutational Burden (bTMB) ≥20 Mutations Per Megabase (Mut/Mb) Analysis Set
- 状态
- 进行中（未招募）
- 最后更新
- 昨天
概览
简要总结
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.
详细描述
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.
研究者
入排标准
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
Standard of Care
Standard of Care chemotherapy treatment
干预措施: Pemetrexed + carboplatin
Standard of Care
Standard of Care chemotherapy treatment
干预措施: Gemcitabine + cisplatin
Combination Therapy
Durvalumab (PD-L1 monoclonal antibody) + Tremelimumab (monoclonal antibody directed against CTLA-4)
干预措施: Durvalumab +Tremelimumab
Standard of Care
Standard of Care chemotherapy treatment
干预措施: Pemetrexed + cisplatin
Standard of Care
Standard of Care chemotherapy treatment
干预措施: Paclitaxel + carboplatin
Standard of Care
Standard of Care chemotherapy treatment
干预措施: Gemcitabine + carboplatin
结局指标
主要结局
Overall Survival (OS); Global Cohort: Blood Tumor Mutational Burden (bTMB) ≥20 Mutations Per Megabase (Mut/Mb) Analysis Set
时间窗: From baseline (Day 1, Week 0) until death due to any cause, assessed up to the Global cohort DCO date (a maximum of approximately 44 months).
The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique.
OS; China Cohort: China Programmed Cell Death Ligand 1 (PD-L1) Negative NSCLC Analysis Set
时间窗: From baseline (Day 1, Week 0) until death due to any cause, assessed up to the China cohort DCO date (a maximum of approximately 44 months).
The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique.
次要结局
- ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets(Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort.)
- OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets(From baseline (Day 1, Week 0) until death due to any cause, assessed up to the Global cohort DCO date (a maximum of approximately 44 months).)
- OS; Global and China Cohorts: FAS, PD-L1 Tumor Cell (TC) ≥25%, and PD-L1 TC ≥50% Analysis Sets(From baseline (Day 1, Week 0) until death due to any cause, assessed up to the Global or China cohort DCO dates, as applicable (a maximum of approximately 44 months) for each cohort.)
- Alive and Progression-Free at 12 Months (APF12); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets(Tumour scans performed at baseline then every 6 weeks up to 12 months.)
- Objective Response Rate (ORR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets(Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months).)
- OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets(Months 12, 18 and 24)
- OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets(Months 12, 18 and 24)
- Serum Concentrations of Durvalumab(Pre-dose and within 1 hour after end of infusion at Week 0 and 12; pre-dose on Week 24 and at follow-up Month 3)
- Serum Concentrations of Tremelimumab(Pre-dose and within 1 hour after end of infusion at Week 0 and 12, and at follow-up Month 3)
- Progression-Free Survival (PFS); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets(Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months).)
- PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets(Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort.)
- Duration of Response (DoR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets(Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months).)
- DoR; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets(Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort.)
- APF12; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets(Tumour scans performed at baseline then every 6 weeks up to 12 months.)
- Time From Randomization to Second Progression or Death (PFS2); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets(Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months).)
- PFS2; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets(Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort.)
- Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab(At Weeks 0, 12, and 24; 3 and 6 months after last dose of study treatment.)
- Number of Participants With ADA Response to Tremelimumab(At Weeks 0 and 12; 3 and 6 months after last dose of study treatment.)