NCT03910127Unknown1 期
A Phase Ib, Multicenter, Randomized Study to Evaluate the Pharmacokinetics, Efficacy and Safety of TQB2450 Combined With or Without Anlotinib in Patients With Advanced Non-small Cell Lung Cancer（NSCLC）
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 入组人数
- 90
- 试验地点
- 3
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
TQB2450 is a humanized monoclonal antibody targeting programmed death ligand-1 (PD-L1), which prevents PD-L1 from binding to PD-1 and B7.1 receptors on T cell surface, restores T cell activity, thus enhancing immune response and has potential to treat various types of tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •1.18 years and older; Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; Life expectancy ≥ 3 months.
- •Histologically or cytologically confirmed Epidermal Growth Factor Receptor (EGFR)/ Anaplastic Lymphoma Kinase (ALK) wild type non-small cell lung cancer.
- •Advanced patients who had received at least first-line of standard chemotherapy but failed or intolerable , with at least one measurable lesion based on RECIST 1.
- •PD-L1-positive tumor status (TPS≥1%) as determined by an immunohistochemistry (IHC) assay based on PD-L1 expression on tumor infiltrating immune cells and/or tumor cells performed by a central laboratory.
- •5.The main organs function are normally, the following criteria are met:
- •routine blood tests：hemoglobin (Hb)≥90g/L (no blood transfusion and blood products within 14 days); absolute neutrophil count (ANC) ≥1.5×109/L; platelets (PLT) ≥80×109/L;
- •Blood biochemical examination: alanine transaminase (ALT) and aspartate aminotransferase (AST)≤ 2.5×ULN (when the liver is invaded，≤ 5×ULN);total bilirubin (TBIL)≤1.5×ULN (Gilbert syndrome patients，≤ 3×ULN)；serum creatinine (Cr) ≤1.5×ULN，or calculated creatinine clearance (CrCl) ≥50ml/min； calculated creatinine clearance formula：Ccr=(140-age)×weight(kg)/72×Scr(mg/dl) Ccr=[(140-age)×weight(kg)]/[0.818×Scr(umol/L) (According to the calculation results , female Patients ×0.85；1 mg/dL = 88.41 umol/ L)
- •Coagulation function: activated partial thromboplastin time (aPTT) ,international normalized ratio (INR) ,prothrombin time (PT) ≤1.5×ULN；
- •left ventricular ejection fraction (LVEF) measured by the Cardiac echocardiography ≥ 50%.
- •Male or female subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study (such as intrauterine devices , contraceptives or condoms) ；No pregnant or breastfeeding women, and a negative pregnancy test are received within 7 days before the randomization.
- •Understood and signed an informed consent form.
排除标准
- •Prior therapy with Anlotinib, anti-programmed cell death (PD)-1, anti-PD-L1 or other immunotherapy against PD-1/PD-L
- •Severe hypersensitivity occurs after administration of other monoclonal antibodies.
- •Diagnosed and/or treated additional malignancy within 5 years prior to randomization with the exception of cured basal cell carcinoma of skin and carcinoma in situ of cervix.
- •Has any active autoimmune disease or history of autoimmune disease, such as autoimmune hepatitis, interstitial pneumonia, enteritis, vasculitis, nephritis, asthma patients who need bronchiectasis for medical intervention; Subjects with the vitiligo without systemic treatment, psoriasis, alopecia, well-controlled type I diabetes mellitus, hypothyroidism stable on hormone replacement will not be excluded from this study.
- •Immunosuppressive therapy with immunosuppressive agents or systemic or absorbable local hormones (dosage > 10 mg/day prednisone or other therapeutic hormones) is required for the purpose of immunosuppression.
- •Has multiple factors affecting oral medication, such as inability to swallow, post-gastrointestinal resection, chronic diarrhea and intestinal obstruction, etc.
- •Has uncontrollable pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
- •Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary with blood vessels is unclear.
- •Has any bleeding or bleeding events ≥ grade 3 or with unhealed wounds, ulcerative , or fractures within 4 weeks prior to the first administration.
- •Has uncontrollable symptoms of brain metastases, spinal cord compression, cancerous meningitis within 8 weeks before the first-dosing, or brain or leptomeningeal disease found by CT or MRI during screening.
- •Has received chemotherapy, surgery, radiotherapy, the last treatment from the first dose less than 4 weeks, or oral targeted drugs for less than 5 half-lives, or oral fluorouracil pyridine drugs for less than 14 days, mitomycin C and nitrosourea for less than 6 weeks. Patients whose adverse events (except alopecia) caused by previous treatment did not recover to ≤ grade
- •Patients with any serious and/or uncontrollable disease, including :
- •Has poor blood pressure control, systolic blood pressure ≥ 150 mmHg, diastolic blood pressure ≥ 90 mmHg;
- •Thrombotic events, ischemic attacks, myocardial infarction, grade 2 congestive heart failure or arrhythmias requiring treatment including QTc ≥ 480ms occurred within 6 months of first administration;
- •Severe active or uncontrolled infections ≥ grade 2;
- •Has known clinical history of liver diseases, including viral hepatitis, known carriers of hepatitis B virus (HBV) must exclude active HBV infection, that is, HBV DNA positive > 1 *104 copies/mL or > 2000 IU/mL, known hepatitis C virus infection (HCV) and HCV RNA positive > 1 *103 copies/mL, or other decompensated hepatitis and chronic hepatitis, which require antiviral treatment;
- •HIV positive;
- •Poor control of diabetes mellitus, fasting blood-glucose ≥ grade 2;
- •Has vaccinated with vaccines or attenuated vaccines within 4 weeks prior to first administration.
- •According to the judgement of the researchers, there are other factors that may lead to the termination of the study.
研究组 & 干预措施
TQB2450 + Anlotinib (10 mg)
Experimental
TQB2450 1200 mg administered intravenously (IV) on Day 1 of each 21-day cycle plus Anlotinib capsules 10 mg given orally in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21)
干预措施: TQB2450 (Drug)
TQB2450 + Anlotinib (10 mg)
Experimental
TQB2450 1200 mg administered intravenously (IV) on Day 1 of each 21-day cycle plus Anlotinib capsules 10 mg given orally in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21)
干预措施: Anlotinib (Drug)
TQB2450 + Anlotinib (12 mg)
Experimental
TQB2450 1200 mg administered IV on Day 1 of each 21-day cycle plus Anlotinib capsules 12 mg given orally in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21)
干预措施: TQB2450 (Drug)
TQB2450 + Anlotinib (12 mg)
Experimental
TQB2450 1200 mg administered IV on Day 1 of each 21-day cycle plus Anlotinib capsules 12 mg given orally in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21)
干预措施: Anlotinib (Drug)
TQB2450 + Placebo
Placebo Comparator
TQB2450 1200 mg administered IV on Day 1 of each 21-day cycle plus Placebo for Anlotinib capsules given orally in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21)
干预措施: TQB2450 (Drug)
TQB2450 + Placebo
Placebo Comparator
TQB2450 1200 mg administered IV on Day 1 of each 21-day cycle plus Placebo for Anlotinib capsules given orally in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21)
干预措施: Anlotinib (Drug)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: up to approximately 18 months
PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause.
次要结局
- Adverse Event （AE）: Drug dose adjustment(up to approximately 18 months)
- Overall response rate （ORR）(up to approximately 18 months)
- Disease control rate（DCR）(up to approximately 18 months)
- Overall survival (OS)(up to approximately 24 months)
- Pharmacokinetics (PK): Maximum Concentration (Cmax)(Hour 0 (before infusion), 30 minutes after start of infusion, 0, 2, 6, 10, 24, 72, 168, 336, 504 hours after end of infusion on cycle 1 and cycle 6 (each cycle is 21 days).)
- Pharmacokinetics (PK): Area Under the Serum Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])(Hour 0 (before infusion), 30 minutes after start of infusion, 0, 2, 6, 10, 24, 72, 168, 336, 504 hours after end of infusion on cycle 1 and cycle 6 (each cycle is 21 days).)
- Pharmacokinetics (PK): t1/2(Hour 0 (before infusion), 30 minutes after start of infusion, 0, 2, 6, 10, 24, 72, 168, 336, 504 hours after end of infusion on cycle 1 and cycle 6 (each cycle is 21 days).)
研究者
研究点 (3)
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