A Randomized, Open-Label, Phase 2 Study of Nivolumab in Combination With Ipilimumab or Nivolumab Monotherapy in Participants With Advanced or Metastatic Solid Tumors of High Tumor Mutational Burden (TMB-H)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 212
- 试验地点
- 120
- 主要终点
- Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) - Arm A
研究概览
简要总结
The purpose of this study is to demonstrate the clinical activity of nivolumab in combination with ipilimumab in multiple types of tumors based on their Tumor Mutational Burden status.
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
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with a refractory, metastatic, or unresectable histologically or cytologically confirmed solid malignant tumor with high tumor mutational burden (TMB-H) who are refractory to standard local therapies, or for which no standard treatment is available.
- •Must be able to provide tissue and blood TMB-H testing results
- •Must have measurable disease for response assessment
排除标准
- •Participants with melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC) or hematological malignancy as primary site of disease
- •Participants who received prior treatment with an anti-programmed death-1 (anti-PD-1), anti-programmed death ligand 1 (anti-PD-L1), anti-programmed death ligand 2 (anti-PD-L2), anti-CD137, or anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
- •Treatment with any chemotherapy, radiation therapy, biologics for cancer, or investigational therapy within 28 days of first administration of study treatment
- •Other protocol defined inclusion/exclusion criteria apply.
结局指标
主要结局
Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) - Arm A
时间窗: From date of randomization up to 42 months
ORR was defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR) based on Blinded Independent Central Review (BICR) assessment. RECIST Criteria: CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR= ≥ 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. RANO Criteria: CR= Disappearance of all enhancing measurable and nonmeasurable disease; stable or improved nonenhancing T2/FLAIR lesions; off corticosteroids; and stable or improved clinically PR= ≥ 50% decrease compared with baseline in the sum of products of perpendicular diameters of all measurable enhancing lesions; no progression of nonmeasureable disease; no new lesions; stable or improved nonenhancing (T2/FLAIR) lesions on same or lower dose of corticosteroids compared with baseline scan; and stable or improved clinically.
次要结局
- Time to Objective Response (TTR) Per Blinded Independent Central Review (BICR)(From date of randomization to date of first confirmed response (CR or PR) (Up to 57 months))
- Clinical Benefit Rate (CBR) Per Blinded Independent Central Review (BICR)(From date of randomization up to 57 months)
- Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) - Arm B(From date of randomization up to 57 months)
- Objective Response Rate (ORR) Per Investigator(From date of randomization up to 57 months)
- Duration of Response (DoR) Per Investigator(From date of randomization to date of first documented tumor progression, or date of death, whichever occurs first (Up to 57 months))
- Duration of Response (DoR) Per Blinded Independent Central Review (BICR)(From date of randomization to date of first documented tumor progression, or date of death, whichever occurs first (Up to 57 months))
- Time to Objective Response (TTR) Per Investigator(From date of randomization to date of first confirmed response (CR or PR) (Up to 57 months))
- Clinical Benefit Rate (CBR) Per Investigator(From date of randomization up to 57 months)
- Progression Free Survival (PFS) Per Blinded Independent Central Review (BICR)(From date of randomization to date of first documented tumor progression, or date of death, whichever occurs first (Up to 57 months))
- Overall Survival (OS)(From date of randomization to date of death (Up to 57 months))
- Progression Free Survival (PFS) Per Investigator(From date of randomization to date of first documented tumor progression, or date of death, whichever occurs first (Up to 57 months))
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(From first dose to 30 days post last dose (Up to 25 months))
- Number of Participants With On-Treatment Laboratory Parameters(From first dose to 30 days post last dose (Up to 25 months))