临床试验/NCT02915432

NCT02915432Unknown1 期

A Multi-Center, Open Label Phase Ib/II Clinical Study to Evaluate JS001 in Patients With Advanced Gastric Adenocarcinoma, Esophageal Squamous Cell Carcinoma, Nasopharyngeal Carcinoma and Head and Neck Squamous Cell Carcinoma

Shanghai Junshi Bioscience Co., Ltd.23 个研究点分布在 1 个国家目标入组 401 人开始时间: 2016年12月1日最近更新: 2021年12月13日

适应症

试验速览

阶段: 1 期
发起方
入组人数: 401
试验地点: 23
主要终点: Objective response rate (ORR) evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验相关资讯

研究概览

简要总结

The purpose of this study is to preliminarily evaluate anti-tumor activity of a Recombinant Humanized Anti-PD-1 Monoclonal Antibody for Infusion (JS001) in treating advanced gastric adenocarcinoma, esophageal squamous cell carcinoma, nasopharyngeal carcinoma and head and neck squamous cell carcinoma and to determine the recommended phase II dose (RP2D)

详细描述

Overall Design:

This is a multicenter, open-label, phase Ib/II clinical study of Toripalimab Injection (JS001) in patients with gastric adenocarcinoma (GC), esophageal squamous cell carcinoma (ESCC), nasopharyngeal carcinoma (NPC), or head and neck squamous cell carcinoma (HNSCC). On the basis of the results of safety and pharmacokinetic data in the phase I study of JS001, 3 mg/kg is determined as the recommended dose of the 2-week monotherapy regimen, and no study on the 10 mg/kg cohorts will be conducted any more. And the corresponding 240 mg and 360 mg are determined as the corresponding exploratory doses of the 3-week combined treatment regimens.

Eligible subjects will be selected based on the inclusion and exclusion criteria: subjects with gastric adenocarcinoma, esophageal squamous cell carcinoma, nasopharyngeal carcinoma, or head and neck squamous cell carcinoma (cohort 1, 2, 3, 4, respectively) will receive treatment at the dose of 3 mg/kg. While subjects with advanced gastric adenocarcinoma, esophageal squamous cell carcinoma, nasopharyngeal carcinoma, or head and neck squamous cell carcinoma (cohort 5, 6, 7, 8, respectively), who have not received any treatment before, will be treated with the corresponding 3-week regimen of standard first-line chemotherapy combined with JS001 240 mg or 360 mg .

Study Treatment:

The study on the 3 mg/kg cohorts is planned to be conducted first in cohort 1, 2, 3, 4 in this trial. After enrollment, the subjects will receive study treatment once every 2 weeks (Q2W) with 4 weeks as a cycle, until absence of further benefits judged by the investigator, disease progression, occurrence of intolerable toxicity, investigator's decision, withdrawal of informed consent by the subject, or death.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Factorial
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

•Subjects may be entered in the study only if they meet all of the following criteria:
•Fully understand the study and signed the Informed Consent Form (ICF) voluntarily;
•Subjects with histologically and/or cytologically confirmed advanced and/or metastatic gastric adenocarcinoma (including adenocarcinoma at esophageal-gastric conjunction), esophageal squamous cell carcinoma, nasopharyngeal carcinoma, or head and neck squamous cell carcinoma, who meet the following conditions (not applicable to cohort 5, 6, 7, and 8):
•Subjects with gastric adenocarcinoma must have received at least one line of anti-tumor treatment for advanced gastric adenocarcinoma and have documented tumor progression or be intolerable to the current available chemotherapy regimen. Subjects who have recurrence or metastasis within 6 months after completion of concomitant adjuvant or neoadjuvant chemotherapy of radical operation are eligible to this study; Subjects with esophageal squamous cell carcinoma must have received at least one line of treatment for advanced esophageal squamous cell carcinoma (including but not limited to anticancer drug treatment or radio-chemotherapy) and have documented tumor progression or be intolerable to the current chemotherapy regimen. Subjects who have recurrence or metastasis within 6 months after completion of concomitant adjuvant or neoadjuvant therapy (including but not limited to chemotherapy or radio-chemotherapy) of radical operation are eligible to this study;
•Subjects with nasopharyngeal carcinoma or head and neck squamous cell carcinoma who have received at least one line of treatment for advanced nasopharyngeal carcinoma or head and neck squamous cell carcinoma (including but not limited to anticancer drug treatment or radio-chemotherapy) and have documented tumor progression or be intolerable to other current chemotherapy regimens. Subjects with recurrence or metastasis within 6 months after completion of concomitant adjuvant or neoadjuvant radio-chemotherapy of radical operation are eligible to this study (only applies for Version 4.1 and the previous ones); while for the working protocol version 5.0, subjects with nasopharyngeal carcinoma can be enrolled only if they meet the following criteria:
•subjects having received at least two lines of treatment for advanced nasopharyngeal carcinoma (including but not limited to anticancer drug treatment and radio-chemotherapy), who are confirmed to have tumor progression or be intolerable to other current chemotherapy regimens; adjuvant or neoadjuvant radio-chemotherapy after radical surgery can be considered as one line of treatment if tumor recurrence or metastasis occurred within 6 months after the end of the radio-chemotherapy.
•At least one measurable lesion (according to RECIST 1.1); Note: Any lesion which received radiotherapy treatment previously cannot be regarded as a target lesion, unless that it has definitely progressed after radiotherapy.
•Agree to provide archived tumor tissue specimens or have biopsy to collect tumor tissues for PD-L1 IHC measurement in the central laboratory;
•Males or females aged between 18 and 75 years old;
•ECOG score of 0-1;
•Life expectancy ≥ 3 months;
•The results of laboratory tests performed within 7 days prior to enrollment must meet the following criteria:
•Neutrophils ≥ 1.5×109/L (not applicable to cohort 5, 6, 7, and 8);
•Platelets ≥ 75×109/L (not applicable to cohort 5, 6, 7, and 8);
•Hemoglobin ≥ 90 g/L (without receiving infusion of concentrated red blood cells within 2 weeks);
•Serum creatinine ≤ 1.5× upper limit of normal (ULN), or creatinine clearance > 50 mL/min (not applicable to cohort 5, 6, 7, and 8);
•Serum total bilirubin ≤ 1.5×ULN (total bilirubin ≤ 3×ULN are acceptable for subjects with Gilbert syndrome);
•Both AST and ALT ≤ 2.5×ULN; ALT and AST ≤ 5×ULN are acceptable for subjects with liver metastasis;
•Serum pregnancy test result must be confirmed as negative for women of childbearing potential within 28 days prior to enrollment and the subjects must agree to take effective contraception measures throughout the study treatment period until 60 days after the end of study treatment. Women of childbearing potential are defined as women with sexual maturity, who meet any of the following conditions: 1) no hysterectomy or bilateral oophorectomy; 2) without natural menopause for a consecutive 24 months (patients with menopause after cancer treatment may also have childbearing potential) (i.e. menstruation occurred at any time during the previous consecutive 24 months) (not applicable to cohort 5, 6, 7, and 8).
•Female partners of childbearing potential of the male subjects should also follow the contraception requirements.
•Other special inclusion criteria for cohort 5, 6, 7, and
•Subjects with histologically and/or cytologically confirmed advanced and/or metastatic gastric adenocarcinoma (including adenocarcinoma at esophageal-gastric conjunction), esophageal squamous cell carcinoma, nasopharyngeal carcinoma, or head and neck squamous cell carcinoma, who meet any of the following conditions:
•Subjects who have not received any systematic treatment.
•Subjects who have received any neoadjuvant chemotherapy, adjuvant chemotherapy for the purpose of curing must experience a period for at least 6 months from the end of the last chemotherapy to tumor progression.
•Subjects with head and neck squamous cell carcinoma must have received radiotherapy for the purpose of curing, and the period from the end of radiotherapy to tumor progression must be at least 1 year.
•For subjects with gastric carcinoma, Her2 negative is required. HER2 positive is defined as IHC 3+ or IHC 2+ combined with ISH+, and ISH positive is defined as the ratio of the number of HER2 gene copies to the number of CEP17 signals ≥ 2.
•Results of laboratory test conducted within 7 days before enrollment must meet the following criteria:
•Neutrophils ≥ 2×109/L; WBC count ≥ 4×109L and < 15×109/L
•Platelets ≥ 100×109/L;
•Hemoglobin ≥ 90 g/L (no infusion of concentrated red blood cells within 2 weeks);
•Creatinine clearance rate > 60 mL/min, based on the predicted value of Cockcroft-Gault glomerular filtration rate:
•(140 - age) × (weight, kg) × (0.85, if females) 72× (serum creatinine, mg/dL) Or: (140 - age) × (weight, kg) × (0.85, if females) 0.818 × (serum creatinine, μmol/L)
•Serum total bilirubin ≤ 1.5 × ULN (total bilirubin ≤ 3 × ULN are acceptable for subjects with Gilbert syndrome);
•INR and aPTT ≤ 1.5 × ULN, applies only to subjects who have not received anticoagulation; and for subjects who are receiving anticoagulation, the dose for anticoagulation must be stable.
•Serum pregnancy test result must be confirmed as negative for women of childbearing potential within 28 days prior to enrollment and the subjects must agree to take effective contraception measures throughout the study treatment period until 6 months after the end of chemotherapy or 60 days after the end of study treatment (whichever comes last). Women of childbearing potential are defined as women with sexual maturities, who meet any of the following conditions: 1) no hysterectomy or bilateral oophorectomy; 2) without natural menopause for a consecutive 24 months (patients with menopause after cancer treatment may also have childbearing potential) (i.e. menstruation occurred at any time during the previous consecutive 24 months) .
•Female partners of childbearing potential of the male subjects should also follow the contraception requirements.
•Subjects fulfilling any of the following conditions cannot be enrolled in the study:
•Known hypersensitivity to citric acid monohydrate, dihydrate sodium citrate, mannitol or polysorbate (components of the investigational drug);
•Anti-tumor treatment with cytotoxic drugs, biological drugs (e.g. monoclonal antibody), immunotherapy (e.g. interleukin 2 or interferon), or other investigational drugs within 4 weeks prior to enrollment;
•Tyrosine kinase inhibitor treatment within 2 weeks prior to enrollment;
•Radiotherapy within 4 weeks prior to enrollment, or radioactive drugs within 8 weeks prior to enrollment. However, patients receiving local palliative radiotherapy for bone metastasis lesions can be included;
•Subjects with any major surgical operation within 4 weeks prior to enrollment or who have not completely recovered from the prior operation (for the definition of major surgical operation, please refer to the Level 3 and Level 4 operations stipulated in the Management of Clinical Application of Medical Technology enforced on May 1, 2009);
•Toxicity due to any previous anticancer treatment has not recovered to CTCAE Grade 0-1, excluding the following conditions:
•Pigmentation;
•Peripheral nerve toxicity recovered to < CTCAE Grade 2 (not applicable to cohort 5, 6, 7, and 8, subjects are not eligible if peripheral neurotoxicity does not restore to normal);
•Long-term toxicity related to radiotherapy, which will not fully recover as judged by the investigator.
•Central nervous system metastasis with clinical symptoms (e.g. brain edema, hormone intervention required, or progression of brain metastasis) and/or carcinomatous meningitis. Subjects with prior treatment for brain or meningeal metastasis can be included if they have remained stable clinically for at least 2 months and systemic hormone treatment (Prednisone at a dose of > 10 mg/day or other equivalent hormone formulations) has been discontinued for more than 4 weeks;
•Subjects with nasopharyngeal carcinoma or head and neck squamous cell carcinoma, who are found to have necrotic lesions by examination within 4 weeks prior to enrollment, for which there is a potential risk of massive hemorrhage as judged by the investigator;
•Previous or other concurrent malignant tumors (expect for effectively controlled non-melanoma skin basal cell carcinoma, breast/cervix carcinoma in situ, and other malignant tumors which were effectively controlled without treatment over the past 5 years);
•Any active autoimmune disease or history of any autoimmune disease (including but are not limited to interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism or hypothyroidism. Patients with vitiligo or asthma (in childhood) which was completely resolved and without need of any intervention in adulthood can be included. However, subjects with asthma which needs bronchodilator for medical intervention cannot be included);
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排除标准

未提供

结局指标

主要结局

Objective response rate (ORR) evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

时间窗: Up to 1.5 approximately years

To preliminarily evaluate the anti-tumor activity of Toripalimab Injection (former name: Recombinant humanized anti-PD-1 monoclonal antibody for injection, JS001) in treating advanced gastric adenocarcinoma, esophageal squamous cell carcinoma, nasopharyngeal carcinoma, and head and neck squamous cell carcinoma.

次要结局

Duration of response (DOR)(Up to 1.5 approximately years)
Disease control rate (DCR)(Up to 1.5 approximately years)
Progression free survival (PFS)(Up to 1.5 approximately years)
Overall survival (OS)(Up to 1.5 approximately years)
afety: incidence and severity of adverse events, and clinically significant laboratory abnormalities(Up to 1.5 approximately years)
The frequencies of positive and negative anti-drug antibody (ADA) test compared with baseline(Up to 1.5 approximately years)
Maximum Plasma Concentration (Cmax) after single dose injection of Anti-PD-1 Monoclonal Antibody (mAb)(Up to 1.5 approximately years)
Peak Time (Tmax) after single dose injection of Anti-PD-1 mAb(Up to 1.5 approximately years)
Area Under the Curve (AUC) after single dose injection of Anti-PD-1 mAb(Up to 1.5 approximately years)
t1/2 after single dose injection of Recombinant Humanized Anti-PD-1 mAb(Up to 1.5 approximately years)
Plasma clearance (CL) after single dose injection of Anti-PD-1 mAb(Up to 1.5 approximately years)
Apparent volume of distribution (V) after single dose injection of Anti-PD-1 mAb(Up to 1.5 approximately years)
Minimum Plasma Concentration (Cmin) of steady state after multiple dose injection of Anti-PD-1 mAb(Up to 1.5 approximately years)
Apparent volume of distribution of steady state (Vss) after multiple dose injection of Anti-PD-1 mAb(Up to 1.5 approximately years)

研究者

发起方

Shanghai Junshi Bioscience Co., Ltd.

申办方类型

Other

责任方

Sponsor

研究点 (23)

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