Phase II Clinical Study of JS207 (PD-1/VEGF Bispecific Antibody) Combination Therapies in Patients With Driver Gene-Positive, Advanced Non-Small Cell Lung Cancer After Failure of TKI Therapy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- Investigator-assessed objective response rate (ORR)
研究概览
简要总结
This study targets patients with advanced NSCLC driven with positive driver genes who have failed TKI treatment, enrolling 66-78 participants. Cohort1 ：Patients will receive JS207 (10 or 15 mg/kg, IV, d1) + pemetrexed (500 mg/m², IV, d1) + platinum-based chemotherapy (carboplatin Area Under the Curve(AUC)5 or cisplatin 75 mg/m², d1) every 3 weeks for 4 cycles. Afterward, JS207 and pemetrexed will continue as maintenance therapy until discontinuation criteria are met. Cohort2 ：The treatment received was JS207 (10mg/kg, intravenous, on day 1) + JS212 (4.2mg/kg or another SMC-selected dose, intravenous, on day 1), every 3 weeks, until the termination criteria were met. The study aims to assess the safety, tolerability, and preliminary efficacy of JS207 combination therapy.
详细描述
This study enrolls patients with advanced non-small cell lung cancer (NSCLC) who have positive driver genes and have failed TKI treatment.
Approximately 66-78 patients are expected to be enrolled and receive treatment. Cohort1 ：JS207 (10 mg/kg or 15 mg/kg, IV, d1) + pemetrexed (500 mg/m², IV, d1) + platinum-based chemotherapy (carboplatin: AUC5, d1 or cisplatin 75 mg/m², d1) every 3 weeks (Q3W) for a total of 4 cycles.After the 4 cycles, patients will continue receiving JS207 (10 mg/kg or 15 mg/kg, IV, d1) + pemetrexed (500 mg/m², IV, d1) every 3 weeks (Q3W) until they meet the criteria for treatment discontinuation. Cohort2 ：The treatment received was JS207 (10mg/kg, intravenous, on day 1) + JS212 (4.2mg/kg or another SMC-selected dose, intravenous, on day 1), every 3 weeks, until the termination criteria were met.
The study aims to assess the safety, tolerability, and preliminary efficacy of JS207 combination therapy.
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
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
- •Age between 18 and 75 years old (both 18 and 75 years old included) at the time of signing the informed consent form, applicable to both males and females.
- •Locally advanced (stage IIIB/IIIC), metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC) confirmed by histology or cytology, which is not eligible for radical surgery or radical chemoradiotherapy.
- •Positive for driver genes, including but not limited to any of the following: EGFR sensitive mutations (18 exon G719X mutation, 19 exon deletion mutation, 20 exon S768I or T790M mutation, 21 exon L858R or L861Q mutation), ALK fusion, ROS1 fusion, BRAF V600E mutation, NTRK fusion, MET14 exon skipping mutation, RET fusion, KRAS G12C mutation, HER-2 mutation, EGFR 20 exon insertion mutation.
- •Previous targeted therapy failed and there is currently no standard targeted treatment available.
- •Cohort1: PD-L1 positive (TPS ≥ 1%) confirmed by the central laboratory or the research center. Cohort2:: Organized samples must be provided for the central laboratory to conduct retrospective biomarker testing (which may include PD-L1, EGFR and HER3 expression).
- •Being able to provide a qualified test report for positive driver gene, or agreeing to provide a qualified sample for driver gene testing.
- •According to the RECIST v1.1 criteria, the subject has at least 1 measurable lesion.
- •Performance status score of 0-1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
- •Expected survival period ≥ 12 weeks.
- •The function of important organs meets the requirements of the protocol.
- •For female subjects with reproductive capacity who have sexual relations with unsterilized male partners, they must agree to have no pregnancy plans and to take effective contraceptive measures during the period from signing the ICF to 7 months after the last administration of JS212, or 6 months after the last administration of JS207 or chemotherapy drugs (whichever is the longer period of contraceptive requirement). For unsterilized male subjects who maintain sexual relations with female partners with reproductive capacity, they must agree to take effective contraceptive measures during the period from signing the ICF to 4 months after the last administration of JS212, or 6 months after the last administration of JS207 or chemotherapy drugs (whichever is the longer period of contraceptive requirement) (Appendix 4). For female patients with reproductive capacity, the HCG test in the 7 days prior to study enrollment must be negative and they must be non-lactating.
- •Voluntarily joining this study, signing the informed consent form, having good compliance, and cooperating with the follow-up.
排除标准
- •Diseases accompanied by those listed in the protocol, including those with histopathological or cytopathological confirmation of the tumor combined with neuroendocrine tumor (including small cell lung cancer, large cell neuroendocrine carcinoma, etc.) components, or with the squamous cell carcinoma component exceeding 10%; known meningeal metastasis; symptomatic brain metastasis; the tumor encircling important blood vessels or with obvious necrosis and cavities, and the investigator deems that it may pose a risk of bleeding, etc.
- •Received the treatments listed in the plan, including immune-mediated treatments; systemic chemotherapy, anti-VEGF pathway target drugs, anti-EGFR and/or HER3 target drugs, and ADC drugs containing topoisomerase inhibitors (only applicable to cohort 2).
- •Having an obvious bleeding tendency or a history of severe coagulation dysfunction.
- •Gastrointestinal perforation, intra-abdominal fistula or intra-abdominal abscess occurred within 6 months before the first administration, or currently having high-risk factors for perforation/fistula formation of the hollow viscus as judged by the investigator.
- •Having a serious, unhealed or ruptured wound, active ulcer or untreated fracture.
- •Having uncontrolled hypertension, or a history of hypertensive crisis or hypertensive encephalopathy.
- •Expected that the toxicity of previous anti-tumor treatment has not recovered to ≤ grade 1 according to the Common Terminology Criteria for Adverse Events (CTCAE).
- •Known allergy to the investigational drug or its excipients, pemetrexed, platinum drugs (carboplatin/cisplatin), or known history of ≥ grade 3 allergy to antibody drugs in the past.
- •Having an active autoimmune disease or a history of autoimmune disease.
- •Having a history of immunodeficiency.
- •Having a severe infection within 4 weeks before the first use of the investigational drug.
- •History of confirmed or suspected interstitial lung disease, idiopathic pulmonary fibrosis, drug-induced pneumonia, idiopathic pneumonia, or other moderate to severe lung diseases that seriously affect lung function.
- •Active pulmonary tuberculosis infection detected by medical history or CT examination.
- •Having active tuberculosis, hepatitis B, or hepatitis C.
- •Having been diagnosed with any other malignant tumor within 5 years before the first use of the investigational drug.
- •Uncontrolled concurrent diseases listed in the protocol.
- •As judged by the investigator, having other severe, acute or chronic medical diseases, mental diseases or laboratory abnormalities that may increase the risk associated with participating in the study, or may interfere with the interpretation of the study results. "
研究组 & 干预措施
JS207 + pemetrexed+ platinum-based chemotherapy
干预措施: JS207 (Drug)
JS207 + pemetrexed+ platinum-based chemotherapy
干预措施: Carboplatin or cisplatin (Drug)
JS207 + pemetrexed+ platinum-based chemotherapy
干预措施: Pemetrexed (Drug)
结局指标
主要结局
Investigator-assessed objective response rate (ORR)
时间窗: Up to approximately 25 months
Evaluate the investigator-assessed objective response rate (ORR) of JS207 combined with pemetrexed and platinum-based chemotherapy in the treatment of advanced non-squamous non-small cell lung cancer (NSCLC) patients with positive driver genes and who have failed tyrosine kinase inhibitor (TKI) therapy.The ORR is defined as the proportion of subjects who have a partial response (PR) or a complete response (CR) in the Best Overall Response
次要结局
- Investigator-assessed objective response rate (DCR)(Up to approximately 25 months)
- Investigator-assessed Duration of Response (DoR)(Up to approximately 25 months)
- Investigator-assessed Progression-Free Survival (PFS)(Up to approximately 25months)
- Investigator-assessed overall survival (OS)(Up to approximately 25 months)
- Adverse Event(Up to approximately 25 months)
- Number of participants with Laboratory examination indices(Up to approximately 25 months)