NCT05020769进行中（未招募）2 期
A Phase II/III Clinical Study to Evaluate the Efficacy and Safety of SI-B001 in Combination With Osimertinib Mesylate Tablets in the Treatment of Recurrent and Metastatic Non- Small Cell Lung Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 14
- 试验地点
- 3
- 主要终点
- ORR
研究概览
简要总结
This multi-center, open label Phase II/III clinical study is performed in patients with locally advanced/metastatic NSCLC progressed on prior EGFR-TKI treatment or with non TKI-sensitizing mutation or patients with EGFR exon20ins mutation. This study is investigating the safety and efficacy of SI-B001 at monotherapy RP2D or lower combined with Osimertinib in patients with locally advanced or metastatic NSCLC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntarily sign the informed consent and follow the requirements of the protocol;
- •Male or female;
- •Age: ≥ 18 years;
- •Expected survival time ≥ 3 months;
- •Patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) confirmed by histopathology and/or cytology, T790M-negative, Exon20ins mutation resistant to the third generation EGFR TKI after the first or second line treatment, or resistance to the first or second generation TKI after the first line treatment;
- •Consent to provide an archived tumor tissue specimen or fresh tissue sample (an FFPE block or approximately 6-12 white slides with a size of 5μm) from the primary or metastatic tumor within 6 months of the date of consent. Participants who were unable to provide tumor tissue samples could be enrolled if they met other inclusion and exclusion criteria after evaluation by investigators.
- •Must have at least one measurable lesion as defined by RECISTv1.1;
- •Performance status score ECOG0 or 1;
- •Toxicity from previous antineochemical therapy has returned to grade 1 or less as defined by NCI-CTCAE v5.0 (asymptomatic laboratory abnormalities such as elevated ALP, hyperuricemia, elevated serum amylase/lipase, and elevated blood glucose were considered by the investigator, and toxicity with no safety risk was judged by the investigator; Except for alopecia, grade 2 peripheral neurotoxicity, and hypothyroidism stable with hormone replacement therapy).
- •No severe cardiac dysfunction, left ventricular score ≥ 50%;
- •The level of organ function must meet the following criteria:
- •Bone marrow function: Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L, platelet count ≥ 80 × 10^9/L, hemoglobin ≥ 90 g/L;
- •Liver function: TBIL ≤ 1.5ULN (total bilirubin ≤ 3ULN for subjects with Gilbert's syndrome, liver cancer or liver metastases); AST and ALT ≤ 2.5ULN for subjects without liver metastases; AST and ALT ≤ 5.0ULN for subjects with liver metastases;
- •Renal function: creatinine (Cr) ≤ 1.5ULN, or creatinine clearance (Ccr) ≥ 50 mL/min (according to CockcroftandGault formula).
- •Coagulation function: international normalized ratio (INR) ≤ 1.5 × ULN, and activated partial thromboplastin time (APTT) ≤ 1.5ULN;
- •Urine protein ≤ 2 + (measured by dipstick) or < 1000 mg/24 h (urine);
- •Premenopausal women of childbearing potential must have a negative serum or urine pregnancy test 7 before starting treatment and must be non-lactating; all patients (male or female) should take adequate barrier contraception measures throughout the treatment cycle and 6 months after the end of treatment.
排除标准
- •Gene sequencing showed that there were MET, ALK, RET, HER2 and other driver gene mutations related to the occurrence and development of tumors.
- •Patients with prior systemic chemotherapy as part of first - or second-line systemic therapy;
- •Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, and major surgery were used within 4 weeks before the first dose, and palliative radiotherapy, targeted therapy (including small molecule tyrosine kinase inhibitors), and other anti-tumor treatments were used within 2 weeks before the first dose.
- •The history of severe heart disease within the past six months was screened, such as symptomatic congestive heart failure (CHF) ≥ grade 2 (CTCAE v5.0), New York Heart Association (NYHA) ≥ grade 2 heart failure, acute coronary syndrome, etc.
- •Prolonged QT interval (QTc > 450 msec in men or QTc > 470 msec in women), complete left bundle branch block, atrioventricular block III degree;
- •Active autoimmune and inflammatory diseases, such as systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory intestinal diseases and Hashimoto's thyroiditis, etc., excluding type I diabetes mellitus, hypothyroidism that can be controlled only by replacement therapy, and skin diseases without systemic treatment (such as vitiligo and psoriasis);
- •Other malignant tumors diagnosed within 5 years before the first dose of treatment, except those with radical basal cell carcinoma, squamous cell carcinoma of the skin, and/or radical resection in situ carcinoma considered by investigators to be eligible;
- •Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg);
- •Pulmonary disease grade ≥3 was defined according to CTCAE v5.0, including dyspnea at rest, or requiring continuous oxygen therapy, or a history of interstitial lung disease (ILD).
- •There were symptoms of active central nervous system metastasis. However, patients with stable parenchymal metastases could be enrolled, and whether they were stable was defined by the investigators.
- •Patients with a history of allergy to the recombinant humanized or human-mouse chimeric antibody or to SI-B001 or any of the excipients of the chemotherapeutic agents used in this trial;
- •A history of autologous or allogeneic stem cell transplantation;
- •The cumulative dose of anthracyclines in previous (new) adjuvant therapy was > 360 mg/m^2;
- •Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number > 10^4) or hepatitis C virus infection (HCV-RNA > the lower limit of detection in the research center);
- •Active infections requiring systemic therapy, such as severe pneumonia, bacteremia, sepsis, etc.;
- •Received other unmarketed investigational drugs or treatments within 4 weeks before study enrollment;
- •Other conditions for trial participation were not considered by the investigator to be appropriate
研究组 & 干预措施
SI-B001 combined with osimertinib_A
Experimental
Patients with locally advanced/metastatic NSCLC progressed on 3rd generation EGFR-TKI treatment.
干预措施: SI-B001 (Drug)
SI-B001 combined with osimertinib_A
Experimental
Patients with locally advanced/metastatic NSCLC progressed on 3rd generation EGFR-TKI treatment.
干预措施: Osimertinib (Drug)
SI-B001 combined with osimertinib_B
Experimental
Patients with locally advanced/metastatic NSCLC progressed on prior EGFR-TKI treatment and with T790M negative mutation.
干预措施: SI-B001 (Drug)
SI-B001 combined with osimertinib_B
Experimental
Patients with locally advanced/metastatic NSCLC progressed on prior EGFR-TKI treatment and with T790M negative mutation.
干预措施: Osimertinib (Drug)
SI-B001 combined with osimertinib_C
Experimental
Patients with locally advanced/metastatic NSCLC and with EGFR exon20ins mutation.
干预措施: SI-B001 (Drug)
SI-B001 combined with osimertinib_C
Experimental
Patients with locally advanced/metastatic NSCLC and with EGFR exon20ins mutation.
干预措施: Osimertinib (Drug)
结局指标
主要结局
ORR
时间窗: Up to approximately 24 months
Objective Response Rate
Optimal combination dose (only Phase IIa)
时间窗: Up to approximately 24 months
Optimal combination dose for SI-B001 and Osimertinib (only IIa)
次要结局
- ADA(Up to approximately 24 months)
- TEAE(Up to approximately 24 months)
- DOR(Up to approximately 24 months)
- PFS(Up to approximately 24 months)
- DCR(Up to approximately 24 months)
- Cmax(Up to approximately 24 months)
- Tmax(Up to approximately 24 months)
- Ctrough(Up to approximately 24 months)
研究者
研究点 (3)
Loading locations...
相似试验
进行中（未招募）
2 期
SI-B001 Combined With Chemotherapy in the Treatment of EGFR/ALK WT Recurrent or Metastatic NSCLC.Non Small Cell Lung CancerNCT05020457Sichuan Baili Pharmaceutical Co., Ltd.69
终止
2 期
SI-B001 as a Single Agent or in Combination With Chemotherapy in the Treatment of Digestive System MalignanciesColorectal CancerNCT05039944Sichuan Baili Pharmaceutical Co., Ltd.7
进行中（未招募）
3 期
A Trial of SHR1701 Plus Chemotherapy in Patients With Gastric or Gastroesophageal CancerGastric or Gastroesophageal Junction CancerNCT04950322Suzhou Suncadia Biopharmaceuticals Co., Ltd.737
进行中（未招募）
2 期
SI-B001 Combined With Irinotecan in the Treatment of Recurrent Metastatic Esophageal Squamous Cell Carcinoma.Esophageal Squamous Cell CarcinomasNCT05022654Sichuan Baili Pharmaceutical Co., Ltd.22
已完成
3 期
A Study of Pertuzumab and Trastuzumab Subcutaneous (SC) Treatment in Combination With a Taxane in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast CancerBreast CancerNCT02019277Hoffmann-La Roche50