A Randomized, Double Blind, Phase 3 Study of Platinum-Based Chemotherapy With or Without INCMGA00012 in First-Line Metastatic Squamous and Nonsquamous Non-Small Cell Lung Cancer (POD1UM-304)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 583
- 试验地点
- 200
- 主要终点
- Overall Survival
研究概览
简要总结
The purpose of this study is to assess the efficacy and safety of platinum-based chemotherapy with or without INCMGA00012 in participants with metastatic squamous and nonsquamous non-small cell lung cancer (NSCLC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed NSCLC (either nonsquamous or squamous) that is Stage IV (AJCC v8).
- •No prior systemic treatment for the advanced/metastatic NSCLC
- •Able to provide a formalin-fixed archival tumor tissue sample during screening, or a fresh tumor biopsy
- •Measurable disease per RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy of at least 3 months.
- •Willingness to avoid pregnancy or fathering children.
- •Adequate organ function as indicated by protocol-specified laboratory values. - Has been fully vaccinated against SARS-CoV-2 or is willing and able to be fully vaccinated against SARS-CoV-2 during the study by starting the vaccination process during screening.
排除标准
- •Clinically significant cardiac disease within 6 months of start of study treatment.
- •Any major surgery within 3 weeks of the first dose of study treatment.
- •Thoracic radiation therapy of > 30 Gy within 6 months of the first dose of study treatment.
- •History of peripheral neuropathy ≥ Grade 2 CTCAE v5 for participants who may receive cisplatin, paclitaxel, or nab-paclitaxel.
- •Untreated central nervous system metastases and/or carcinomatous meningitis.
- •Evidence or history of interstitial lung disease or noninfectious pneumonitis that required systemic steroids.
- •Active infection requiring systemic therapy or active tuberculosis. Note: If required by country or local regulations to be tested for COVID-19 during screening, a participant should be excluded if they have a positive test result for SARS CoV-2 infection until both the retesting result is negative and clinical recovery is obtained.
- •Superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers.
- •Has contraindications to chemotherapy agents used in the study.
- •Has an active autoimmune disease that has required systemic treatment in past 2 years.
- •Is receiving systemic antibiotics or steroid therapy ≤ 7 days prior to the first dose of study treatment.
- •Has received a live vaccine within 30 days before the first dose of study treatment (and until 90 days after last dose of study drug).
- •Note: While based on approved SARS-CoV-2 vaccines available worldwide, many vaccines are not live (mRNA and adenovirus vaccines do not contain live virus), if a live vaccine against SARS-CoV-2 is the only available option, prior consultation with the medical monitor should be obtained.
- •Has known active HBV or HCV (testing must be performed to determine eligibility)
研究组 & 干预措施
Placebo + chemotherapy (nonsquamous NSCLC)
Placebo with pemetrexed + cisplatin OR carboplatin followed by placebo plus pemetrexed until progression. Participants assigned to placebo + chemotherapy will have the option of receiving open-label monotherapy INCMGA00012 in a crossover period after documentation of progressive disease.
干预措施: Pemetrexed (Drug)
INCMGA00012 + chemotherapy (squamous NSCLC)
INCMGA00012 with carboplatin + paclitaxel OR nab-paclitaxel followed by INCMGA00012 until progression.
干预措施: Retifanlimab (Drug)
Placebo + chemotherapy (squamous NSCLC)
Placebo with carboplatin + paclitaxel OR nab-paclitaxel followed by placebo until progression. Participants assigned to placebo + chemotherapy will have the option of receiving open-label monotherapy INCMGA00012 in a crossover period after documentation of progressive disease.
干预措施: Carboplatin (Drug)
Placebo + chemotherapy (squamous NSCLC)
Placebo with carboplatin + paclitaxel OR nab-paclitaxel followed by placebo until progression. Participants assigned to placebo + chemotherapy will have the option of receiving open-label monotherapy INCMGA00012 in a crossover period after documentation of progressive disease.
干预措施: Paclitaxel (Drug)
Placebo + chemotherapy (squamous NSCLC)
Placebo with carboplatin + paclitaxel OR nab-paclitaxel followed by placebo until progression. Participants assigned to placebo + chemotherapy will have the option of receiving open-label monotherapy INCMGA00012 in a crossover period after documentation of progressive disease.
干预措施: nab-Paclitaxel (Drug)
Placebo + chemotherapy (nonsquamous NSCLC)
Placebo with pemetrexed + cisplatin OR carboplatin followed by placebo plus pemetrexed until progression. Participants assigned to placebo + chemotherapy will have the option of receiving open-label monotherapy INCMGA00012 in a crossover period after documentation of progressive disease.
干预措施: Placebo (Drug)
Placebo + chemotherapy (squamous NSCLC)
Placebo with carboplatin + paclitaxel OR nab-paclitaxel followed by placebo until progression. Participants assigned to placebo + chemotherapy will have the option of receiving open-label monotherapy INCMGA00012 in a crossover period after documentation of progressive disease.
干预措施: Placebo (Drug)
INCMGA00012 + chemotherapy (squamous NSCLC)
INCMGA00012 with carboplatin + paclitaxel OR nab-paclitaxel followed by INCMGA00012 until progression.
干预措施: nab-Paclitaxel (Drug)
Placebo + chemotherapy (nonsquamous NSCLC)
Placebo with pemetrexed + cisplatin OR carboplatin followed by placebo plus pemetrexed until progression. Participants assigned to placebo + chemotherapy will have the option of receiving open-label monotherapy INCMGA00012 in a crossover period after documentation of progressive disease.
干预措施: Cisplatin (Drug)
INCMGA00012 + chemotherapy (nonsquamous NSCLC)
INCMGA00012 with pemetrexed + cisplatin OR carboplatin followed by INCMGA00012 plus pemetrexed until progression.
干预措施: Cisplatin (Drug)
INCMGA00012 + chemotherapy (nonsquamous NSCLC)
INCMGA00012 with pemetrexed + cisplatin OR carboplatin followed by INCMGA00012 plus pemetrexed until progression.
干预措施: Carboplatin (Drug)
INCMGA00012 + chemotherapy (nonsquamous NSCLC)
INCMGA00012 with pemetrexed + cisplatin OR carboplatin followed by INCMGA00012 plus pemetrexed until progression.
干预措施: Retifanlimab (Drug)
INCMGA00012 + chemotherapy (nonsquamous NSCLC)
INCMGA00012 with pemetrexed + cisplatin OR carboplatin followed by INCMGA00012 plus pemetrexed until progression.
干预措施: Pemetrexed (Drug)
Placebo + chemotherapy (nonsquamous NSCLC)
Placebo with pemetrexed + cisplatin OR carboplatin followed by placebo plus pemetrexed until progression. Participants assigned to placebo + chemotherapy will have the option of receiving open-label monotherapy INCMGA00012 in a crossover period after documentation of progressive disease.
干预措施: Carboplatin (Drug)
INCMGA00012 + chemotherapy (squamous NSCLC)
INCMGA00012 with carboplatin + paclitaxel OR nab-paclitaxel followed by INCMGA00012 until progression.
干预措施: Carboplatin (Drug)
INCMGA00012 + chemotherapy (squamous NSCLC)
INCMGA00012 with carboplatin + paclitaxel OR nab-paclitaxel followed by INCMGA00012 until progression.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Overall Survival
时间窗: up to 39.1 months
Overall survival was defined as the time between the date of randomization and the date of death due to any cause.
次要结局
- Duration of Response(up to 34.3 months)
- Number of Participants With Any Treatment-emergent Adverse Event (TEAE) in the Randomized Treatment Period(up to approximately 39 months)
- Number of Participants Who Discontinued Study Drug Due to TEAEs in the Randomized Treatment Period(up to approximately 39 months)
- Number of Participants With Any TEAE in the Monotherapy Treatment Period(up to approximately 27 months)
- Number of Participants Who Discontinued Study Drug Due to TEAEs in the Monotherapy Treatment Period(up to approximately 27 months)
- Duration of Response(up to 34.3 months)
- Number of Participants With Any Treatment-emergent Adverse Event (TEAE) in the Randomized Treatment Period(up to approximately 39 months)
- Number of Participants Who Discontinued Study Drug Due to TEAEs in the Monotherapy Treatment Period(up to approximately 27 months)
- Cmax1 of Retifanlimab When Administered With Chemotherapy(Cycle 1 Day 1: pre-infusion and immediately after infusion)
- Number of Participants Who Discontinued Study Drug Due to TEAEs in the Randomized Treatment Period(up to approximately 39 months)
- Number of Participants With Any TEAE in the Monotherapy Treatment Period(up to approximately 27 months)
- Cmaxss of Retifanlimab When Administered With Chemotherapy(Cycle 1 Day 1 (C1D1): pre-infusion and immediately after infusion (IAI). C2D1: pre-infusion. C4D1: pre-infusion and IAI. C6D11: pre-infusion. C8D1, and every 4 cycles thereafter: pre-infusion. End of treatment visit and 30-day safety follow-up visit.)
- AUC1 of Retifanlimab When Administered With Chemotherapy(Cycle 1 Day 1: pre-infusion and immediately after infusion)
- AUCss of Retifanlimab When Administered With Chemotherapy(Cycle 1 Day 1 (C1D1): pre-infusion and immediately after infusion (IAI). C2D1: pre-infusion. C4D1: pre-infusion and IAI. C6D11: pre-infusion. C8D1, and every 4 cycles thereafter: pre-infusion. End of treatment visit and 30-day safety follow-up visit.)
- Progression-free Survival (PFS)(up to 35.8 months)
- Objective Response Rate(up to 35.78 months)