A Phase I/II Study Evaluating the Safety, Tolerability, and Efficacy of GLS-012 and GLS-010 in Patients With Advanced Non-Small Cell Lung Cancer (Triumph-02)
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 152
- 试验地点
- 1
- 主要终点
- DLT/MTD
研究概览
简要总结
This is a multicenter, open Phase I/II study. The trial consists of two parts, Part1 is a dose-escalation/expansion study, Part2 is a combination of GLS-010 and GLS-010+GLS-012 with standard chemotherapy for advanced non-small-cell lung cancer respectively to assess preliminary efficacy at the combination dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Part1 section is a dose-escalation/expansion study in a single-arm setup； Part2 section sets up a control； All processes do not involve blind settings.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects enroll in the study and sign the Informed Consent Form (ICF);
- •Aged ≥18 years and ≤75 years;
- •histologically or cytologically confirmed advanced non-small cell lung cancer without driver genes (diagnostic criteria refer to AJCC 8th edition of squamous or non-squamous non-small cell lung cancer);
- •Subjects with an Eastern Cooperative Oncology Group (ECOG) score of 0 ~1 for physical status;
- •expected survival ≥ 12 weeks;
- •Subjects with measurable lesions (at least 1 extracranial lesion) according to the Solid Tumor Evaluation Criteria (RECIST v1.1).
- •Subjects provide formalin-fixed, paraffin-embedded tumor tissue blocks or unstained tumor specimen sections (at least 6), either archived or freshly obtained within 5 years prior to the first study treatment (freshly obtained is preferred);
- •Organ function meets the following criteria:
- •Adequate bone marrow reserve (not acceptable for corrective therapy with hematologic products or cell growth factors administered within 14 days prior to first study dose): absolute neutrophil count ≥ 1.5 x 109/L, platelet count ≥ 90 x 109/L, and hemoglobin ≥ 9 g/dL;
- •Liver: serum albumin ≥ 3.0 g/dL; total bilirubin ≤ 1.5 times the Upper Limit of Normal (ULN), and ALT and AST ≤ 3 times the ULN (or AST and ALT ≤ 5 × ULN for patients with known liver metastases);
- •Renal: blood creatinine ≤ 1.25 times ULN;
- •Heart: left ventricular ejection fraction (LVEF) ≥ 50%.
- •Subjects of childbearing potential must be using highly effective contraception during the study and for at least 6 months after the last dose; female subjects of childbearing potential must have a negative blood pregnancy test within 3 days prior to study enrollment.
排除标准
- •Severe immunotherapy-related toxicity during prior treatment with anti-ICIs;
- •Prior grade ≥ 3 irAE on immunotherapy and who have not recovered to grade ≤ 1 from the last adverse reaction to antineoplastic therapy;
- •With primary or secondary immunodeficiency；
- •Any active, known or suspected autoimmune disease;
- •Known CNS metastases ;
- •Prior severe allergic reactions to large protein preparations/monoclonal antibodies (CTCAE V5.0 classification ≥ grade 4);
- •Previous treatment with anti-LAG-3 antibodies;
- •Other malignant tumors within 5 years prior to screening, except cured cervical carcinoma in situ and cured basal cell carcinoma of the skin;
- •Have uncontrolled cardiac clinical symptoms or disease；
- •Subjects have received a live attenuated vaccine (except inactivated viral seasonal influenza vaccine and novel coronavirus vaccine) within 4 weeks prior to the first dose and who will not receive intranasally administered live attenuated influenza vaccine;
- •Pregnant or nursing females；
- •Poorly compliant or otherwise unsuitable for participation in this study.
研究组 & 干预措施
Phase I Dose-Escalation Stage：GLS-012+GLS-010
Participants will be treated with escalating doses of GLS-010 + GLS-012 to determine the MTD
干预措施: GLS-012+GLS-010 (Drug)
Phase I Expansion Stage：GLS-012+GLS-010
Participants will be enrolled in the expansion stage to better characterize the safety, tolerability, PK variability, and preliminary efficacy of GLS-012+GLS-010 in Advanced Non-Small Cell Lung Cancer.
干预措施: GLS-012+GLS-010 (Drug)
GLS-012+GLS-010+pemetrexed + carboplatin
Participants will be enrolled in the expansion stage to better characterize the safety, PK variability, and preliminary efficacy of GLS-012+GLS-010+pemetrexed+carboplatin in Advanced Non-Small Cell Lung Cancer.
干预措施: GLS-012+GLS-010+pemetrexed+carboplatin (Drug)
GLS-012+GLS-010+paclitaxel+carboplatin
Participants will be enrolled in the expansion stage to better characterize the safety, PK variability, and preliminary efficacy of GLS-012+GLS-010+paclitaxel+carboplatin in Advanced Non-Small Cell Lung Cancer.
干预措施: GLS-012+GLS-010+paclitaxel+carboplatin (Drug)
结局指标
主要结局
DLT/MTD
时间窗: 24 months
To evaluate GLS-012 in combination with GLS-010 dose-limiting toxicity (DLT)/maximum tolerated dose (MTD) in patients with advanced non-small cell lung cancer
Investigator Assessments of Overall Response Rate(ORR)
时间窗: 24 months
RECIST v1.1 will be used to determine ORR by investigator
次要结局
- PFS (progression-free survival)(24 months)
- Disease Control Rate(DCR)(24 months)