A Phase II Clinical Trial of Tiragolumab in Combination With Atezolizumab in Patients With Non-small Cell Lung Cancer (NSCLC) and Untreated Brain Metastases.
概览
- 阶段
- 2 期
- 干预措施
- Tiragolumab
- 疾病 / 适应症
- Non-small Cell Lung Cancer
- 发起方
- Liza Villaruz, MD
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Rate of Initiation of Salvage Radiation Therapy to Central Nervous System (CNS)
- 状态
- 终止
- 最后更新
- 3个月前
概览
简要总结
This clinical trial is aimed at the evaluation of the safety and clinical activity of tiragolumab in combination with atezolizumab with or without chemotherapy in the first line treatment of metastatic non-squamous NSCLC patients with asymptomatic untreated brain metastases.
详细描述
This is a phase II clinical trial aimed at the evaluation of the safety and clinical activity of tiragolumab in combination with atezolizumab with or without chemotherapy in the first line treatment of metastatic non-squamous NSCLC patients with asymptomatic untreated brain metastases. Patients with at least one untreated evaluable brain metastasis of 5 mm or more will be enrolled. Lesions previously treated with SRS may not be used as target lesions. Patients will be required to undergo an on-treatment brain MRI at three weeks for safety purposes. Additional restaging will occur at nine-week intervals. PD-L1 tumor proportion score (TPS) will be determined utilizing an FDA-approved test by local testing.
研究者
Liza Villaruz, MD
Associate Professor of Medicine
University of Pittsburgh
入排标准
入选标准
- •Patients must have histologically or cytologically confirmed non-squamous NSCLC.
- •In patients treated with the combination of tiragolumab and atezolizumab, patients must have PDL1 TPS \>50%, as determined by an FDA-approved test.
- •Patients must have asymptomatic brain metastases with at least one untreated evaluable (per RANO-BM) brain metastasis of 5 mm or more. A growing lesion previously treated with whole brain radiotherapy is acceptable given the lower incidence of radiation necrosis. Lesions previously treated with SRS may not be used as target lesions.
- •o Patients are not required to have measurable disease outside the CNS per RECIST 1.
- •Prior chemotherapy, immunotherapy or radiation given with curative intent in early stage or locoregionally advanced NSCLC is permitted, if completed more than 12 months prior to initiation of study treatment.
- •Prior radiation with palliative intent in the metastatic setting to non-CNS lesions is permitted (no wash-out period).
- •Age ≥18 years.
- •ECOG performance status ≤
- •Life expectancy ≥12 weeks.
- •Patients must have normal organ and marrow function as defined below:
排除标准
- •Symptoms related to brain metastases requiring CNS radiation ≤ 2 weeks of treatment initiation are exclusionary. Steroids greater than prednisone 10 mg/d or equivalent, or anti-epileptic therapy ≤ 2 weeks of treatment initiation are exclusionary.
- •Prior systemic therapy for metastatic disease is not allowed.
- •Patients whose tumors harbor oncogenic drivers with an approved 1st line therapy (e.g. EGFR, ALK, and ROS1 alterations) are excluded.
- •Patients who are receiving any other investigational agents.
- •Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
- •Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study.
- •Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
- •Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
- •Rash must cover \< 10% of body surface area
- •Disease is well controlled at baseline and requires only topical corticosteroids
研究组 & 干预措施
Single Treatment Arm
Tiragolumab in combination with atezolizumab, pemetrexed, and carboplatin.
干预措施: Tiragolumab
Single Treatment Arm
Tiragolumab in combination with atezolizumab, pemetrexed, and carboplatin.
干预措施: Atezolizumab
Single Treatment Arm
Tiragolumab in combination with atezolizumab, pemetrexed, and carboplatin.
干预措施: Pemetrexed
Single Treatment Arm
Tiragolumab in combination with atezolizumab, pemetrexed, and carboplatin.
干预措施: Carboplatin
结局指标
主要结局
Rate of Initiation of Salvage Radiation Therapy to Central Nervous System (CNS)
时间窗: Up to 18 weeks
The proportion of patients that require salvage radiation therapy to the CNS (within 18 weeks from study initiation). Salvage radiation therapy is radiation treatment given for suspected recurrent malignant disease.
次要结局
- Objective Response Rate (ORR)(Up to 26 months)
- Progression-free Survival (PFS)(Up to 5 years)
- Progression-free Survival after initiation of salvage XRT (PFS2)(Up to 5 years)
- Adverse Events Related to Treatment(Up to 26 months)
- Brain Metastasis Response Rate (BMRR)(Up to 26 months)
- Overall Survival (OS)(Up to 5 years)
- PD-L1 Tumor Proportion Score (TPS)(Up to 26 months)