A Multicenter Phase II Randomized Trial Of Immunotherapy Versus Chemotherapy Guided By Circulating Tumor DNA-Based Molecular Response On Patients With Metastatic NSCLC
概览
- 阶段
- 2 期
- 干预措施
- Nivolumab
- 疾病 / 适应症
- Carcinoma, Non-Small-Cell Lung
- 发起方
- Hackensack Meridian Health
- 入组人数
- 108
- 试验地点
- 3
- 主要终点
- Progression Free Survival (PFS)
- 状态
- 招募中
- 最后更新
- 2个月前
概览
简要总结
This clinical trial plans to assess to what extent the on-treatment circulating tumor DNA (ctDNA) can predict the subset of patients with NSCLC who will respond to immunotherapy treatment only and which patients will need both immunotherapy and chemotherapy modalities for their treatment regimen.
详细描述
Subjects will be randomized 2:1 and patients in both arms will begin treatment with nivolumab 360 mg intravenously every 3 weeks and ipilimumab 1 mg/kg intravenously every 6 weeks. At five weeks of treatment, subjects will have ctDNA response evaluation with Guardant360 Response assay. At the next cycle of treatment (+/- 2 days), patients in the larger arm will receive treatment based on the Guardant360 Response assay results, as described below. Subjects will undergo ctDNA evaluation with Guardant360 Response assay 6- week post-randomization and at the time of progression. Response to therapy will be assessed by interval imaging with CT scan of the chest/abdomen/pelvis (and MRI brain if applicable) with response evaluated by irRECIST criteria every 12 weeks until disease progression.
研究者
入排标准
入选标准
- •Eligible patients will have newly diagnosed, previously untreated histologically documented Stage IV NSCLC
- •Eligible patients will be required to have positive PD-L1 expression ≥1% by IHC using Dako 22C3 assay.
- •Patients will require a baseline Guardant360 CDx test prior to enrollment
- •Patients willing to undergo serial ctDNA testing as required by protocol
- •Patients will be over the age of 18
- •Life expectancy ≥12 weeks
- •Measurable (RECIST 1.1) indicator lesion not previously irradiated, with measurable disease determined per the treating investigator.
- •Prior palliative radiotherapy to non-CNS lesions must have been completed at least 2 weeks prior to randomization
- •ECOG Performance Score ≤2
- •Adequate organ function
排除标准
- •Patients under the age of 18
- •Inability to provide informed consent by either the patient or the authorized representative
- •Patients with known EGFR, ALK, ROS1, MET, and RET oncogenic driver alterations that have approved first-line targeted therapies are excluded from the study (All patients must have a tissue or blood-based testing to identify these driver alterations)
- •Patients with no detectable ctDNA or ctDNA VAF ≤ 0.3% on Guardant360 CDx at baseline
- •Subjects with untreated CNS metastases are excluded.
- •Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to randomization. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to randomization.
- •Subjects with carcinomatous meningitis
- •Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before randomization
- •Subjects with previous malignancies (except non-melanoma skin cancers, and in situ cancers such as the following: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to randomization and no additional therapy is required or anticipated to be needed during the study period.
- •Other active malignancy requiring concurrent intervention.
研究组 & 干预措施
Arm A
Arm A - Intervention arm (Immunotherapy and Chemotherapy) Nivolumab 360 mg/kg every 3 weeks Ipilimumab 1 mg/kg every 6 weeks Platinum- doublet Chemotherapy (Histology-based) 4 cycles depending on the investigator's discretion. Carboplatin dosed at AUC 5, and either Paclitaxel 175 mg/m2 for squamous or Pemetrexed 500 mg/m2 for non-squamous
干预措施: Nivolumab
Arm A
Arm A - Intervention arm (Immunotherapy and Chemotherapy) Nivolumab 360 mg/kg every 3 weeks Ipilimumab 1 mg/kg every 6 weeks Platinum- doublet Chemotherapy (Histology-based) 4 cycles depending on the investigator's discretion. Carboplatin dosed at AUC 5, and either Paclitaxel 175 mg/m2 for squamous or Pemetrexed 500 mg/m2 for non-squamous
干预措施: Ipilimumab
Arm A
Arm A - Intervention arm (Immunotherapy and Chemotherapy) Nivolumab 360 mg/kg every 3 weeks Ipilimumab 1 mg/kg every 6 weeks Platinum- doublet Chemotherapy (Histology-based) 4 cycles depending on the investigator's discretion. Carboplatin dosed at AUC 5, and either Paclitaxel 175 mg/m2 for squamous or Pemetrexed 500 mg/m2 for non-squamous
干预措施: Carboplatin
Arm A
Arm A - Intervention arm (Immunotherapy and Chemotherapy) Nivolumab 360 mg/kg every 3 weeks Ipilimumab 1 mg/kg every 6 weeks Platinum- doublet Chemotherapy (Histology-based) 4 cycles depending on the investigator's discretion. Carboplatin dosed at AUC 5, and either Paclitaxel 175 mg/m2 for squamous or Pemetrexed 500 mg/m2 for non-squamous
干预措施: Paclitaxel
Arm A
Arm A - Intervention arm (Immunotherapy and Chemotherapy) Nivolumab 360 mg/kg every 3 weeks Ipilimumab 1 mg/kg every 6 weeks Platinum- doublet Chemotherapy (Histology-based) 4 cycles depending on the investigator's discretion. Carboplatin dosed at AUC 5, and either Paclitaxel 175 mg/m2 for squamous or Pemetrexed 500 mg/m2 for non-squamous
干预措施: Pemetrexed
Arm B
Arm B - control arm (Immunotherapy only) Nivolumab 360 mg/kg every 3 weeks Ipilimumab 1 mg/kg every 6 weeks
干预措施: Nivolumab
Arm B
Arm B - control arm (Immunotherapy only) Nivolumab 360 mg/kg every 3 weeks Ipilimumab 1 mg/kg every 6 weeks
干预措施: Ipilimumab
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Time from randomization to objective disease progression, or death from any cause, whichever first, up to 36 months
To compare progression free survival in patients with on-treatment-ctDNA guided therapy continuation or escalation by addition of platinum-doublet chemotherapy to therapy continuation with Nivolumab-Ipilimumab regardless of on-treatment-ctDNA results.
次要结局
- Progression Free Survival on Subsequent line of therapy (PFS2)(Duration of time from randomization to second objective disease progression, or death from any cause, whichever first, up to 36 months)
- Overall Survival(Duration of time from first treatment to time of death, up to 36 months)
- Safety and Tolerability(All analyses will be conducted using the 30-day safety window)
- Duration of Response(Duration of time between the date of first confirmed response to the date of the first documented tumor progression (per irRECIST), or death due to any cause, whichever occurs first, up to 36 months)
- Objective Response Rate(Duration of time between the date of first treatment and the date of objectively documented progression per irRECIST or the date of initiation of palliative local therapy or the date of subsequent anti-cancer therapy, whichever occurs first, up to 36 mo)