A Phase Ib/II Platform Trial of Newly Emerging Immunotherapy for Pancreatic Cancer Treatment
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 117
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR) (phase II)
研究概览
简要总结
This is a Phase Ib/II platform clinical study to evaluate the initial efficacy and safety of different novel immunotherapies in patients with advanced pancreatic cancer.
详细描述
The cohort A/B/C included patients with unresectable locally advanced or metastatic pancreatic cancer who had previously failed at least first line gemcitabine-based system therapy.The cohort D/E/F included patients with previously untreated systemic pancreatic cancer with unresectable locally advanced or metastatic pancreatic cancer.This study plans to first explore A/B/C cohort, and then start the D/E/F cohort after determining the safety.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Voluntary participation, written informed consent, complied well and cooperated with the follow-up visits;
- •Age ≥ 18 years old, female or male individuals;
- •Eastern Cooperative Oncology Group (ECOG) Performance status score of 0 or 1, the expected survival is more than 3 months;
- •Patients with locally advanced unresectable or metastatic pancreatic cancer confirmed by histopathology or cytopathology (islet cell tumor is not eligible for inclusion) who meet the following requirements:
- •For the A/B/C/ cohort: Had failed of at least first-line systemic therapy; disease recurrence or progression within 6 months of the last treatment of neoadjuvant or adjuvant chemotherapy was also allowed to be enrolled;
- •For the D/E/F cohort: No prior systemic treatment; patients with recurrence or progression of disease more than 6 months after the last treatment of neoadjuvant or adjuvant chemotherapy were also allowed to be enrolled;
- •Had at least one measurable lesion according to RECIST v1.
- •Patients had adequate major organs function;
- •Women of childbearing potential must undergo serum pregnancy test within 7 days prior to the first dose and the result must be negative. Female subjects of childbearing potential and male subjects whose partners are women of childbearing potential must agree to use highly effective contraceptive methods during the study period and within 180 days after the last dose of study drug.
排除标准
- •Previously received drugs with the same target as the planned investigational therapy;
- •radiotherapy (except for palliative reasons), endocrine therapy, chemotherapy, immunotherapy, or molecular targeted therapy within 4 weeks prior to initial administration, except for bisphosphonates (which can be used for bone metastasis);
- •Uncontrolled central nervous system metastases (meaning symptoms or the use of glucocorticoids or mannitol to control symptoms);
- •A history of clinically significant or uncontrolled heart disease, including congestive heart failure, angina pectoris, myocardial infarction, or ventricular arrhythmia, in the 6 months prior to initial dosing;
- •Patients with Grade 1 and above adverse reactions caused by previous treatment, including Grade 1 peripheral neurotoxicity; hair loss is not included and the investigator should clearly record the reasons;
- •Malignant tumors within 5 years prior to the first dose (except for cured skin basal cell carcinoma and cervical carcinoma in situ);
- •Active autoimmune disease requiring systemic treatment within 2 years prior to first administration, except for vitiligo, type I diabetes, residual hypothyroidism due to autoimmune thyroiditis requiring hormone replacement therapy only;
- •History of rapid allergic reaction, eczema or asthma that cannot be controlled by topical corticosteroids;
- •Patients who have lung disease, such as drug-induced interstitial lung disease or pneumonia, obstructive pulmonary disease that severely affects lung function, and symptomatic bronchospasm;
- •Serious infections requiring antibiotic treatment within 14 days prior to initial administration (>CTCAE grade 2), such as severe pneumonia, bacteremia, comorbidifications, etc., resulting in the need for hospitalization;
- •Vaccination of live vaccine within 4 weeks before the first dose or during the study period;
- •Known human immunodeficiency virus (HIV) infection, allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
- •History of prior allergy to any component or excipient of the investigational drug to be received;
- •Other conditions assessed by the investigator as unsuitable for participation in the trial.
研究组 & 干预措施
Cohort1: JS004+JS001+Irinotecan Liposome Injection+5-fluorouracil (5-FU)/leucovorin (LV)
Participants with unresectable locally advanced or metastatic pancreatic cancer who had previously failed at least first line gemcitabine-based system therapy will receive JS004 and JS001 combined with chemotherapy (irinotecan liposome injection+5-FU/LV) until the treatment termination event specified in the protocol occurs.
干预措施: JS001 (Drug)
Cohort1: JS004+JS001+Irinotecan Liposome Injection+5-fluorouracil (5-FU)/leucovorin (LV)
Participants with unresectable locally advanced or metastatic pancreatic cancer who had previously failed at least first line gemcitabine-based system therapy will receive JS004 and JS001 combined with chemotherapy (irinotecan liposome injection+5-FU/LV) until the treatment termination event specified in the protocol occurs.
干预措施: JS004 (Drug)
Cohort1: JS004+JS001+Irinotecan Liposome Injection+5-fluorouracil (5-FU)/leucovorin (LV)
Participants with unresectable locally advanced or metastatic pancreatic cancer who had previously failed at least first line gemcitabine-based system therapy will receive JS004 and JS001 combined with chemotherapy (irinotecan liposome injection+5-FU/LV) until the treatment termination event specified in the protocol occurs.
干预措施: Irinotecan Liposome Injection (Drug)
Cohort1: JS004+JS001+Irinotecan Liposome Injection+5-fluorouracil (5-FU)/leucovorin (LV)
Participants with unresectable locally advanced or metastatic pancreatic cancer who had previously failed at least first line gemcitabine-based system therapy will receive JS004 and JS001 combined with chemotherapy (irinotecan liposome injection+5-FU/LV) until the treatment termination event specified in the protocol occurs.
干预措施: 5-Fluorouracil (5-FU) (Drug)
Cohort1: JS004+JS001+Irinotecan Liposome Injection+5-fluorouracil (5-FU)/leucovorin (LV)
Participants with unresectable locally advanced or metastatic pancreatic cancer who had previously failed at least first line gemcitabine-based system therapy will receive JS004 and JS001 combined with chemotherapy (irinotecan liposome injection+5-FU/LV) until the treatment termination event specified in the protocol occurs.
干预措施: Leucovorin (LV) (Drug)
Cohort2: JS007+JS001+Irinotecan Liposome Injection+5-FU/LV
Participants with unresectable locally advanced or metastatic pancreatic cancer who had previously failed at least first line gemcitabine-based system therapy will receive JS007 and JS001 combined with chemotherapy (irinotecan liposome injection+5-FU/LV) until the treatment termination event specified in the protocol occurs.
干预措施: JS001 (Drug)
Cohort2: JS007+JS001+Irinotecan Liposome Injection+5-FU/LV
Participants with unresectable locally advanced or metastatic pancreatic cancer who had previously failed at least first line gemcitabine-based system therapy will receive JS007 and JS001 combined with chemotherapy (irinotecan liposome injection+5-FU/LV) until the treatment termination event specified in the protocol occurs.
干预措施: JS007 (Drug)
Cohort2: JS007+JS001+Irinotecan Liposome Injection+5-FU/LV
Participants with unresectable locally advanced or metastatic pancreatic cancer who had previously failed at least first line gemcitabine-based system therapy will receive JS007 and JS001 combined with chemotherapy (irinotecan liposome injection+5-FU/LV) until the treatment termination event specified in the protocol occurs.
干预措施: Irinotecan Liposome Injection (Drug)
Cohort2: JS007+JS001+Irinotecan Liposome Injection+5-FU/LV
Participants with unresectable locally advanced or metastatic pancreatic cancer who had previously failed at least first line gemcitabine-based system therapy will receive JS007 and JS001 combined with chemotherapy (irinotecan liposome injection+5-FU/LV) until the treatment termination event specified in the protocol occurs.
干预措施: 5-Fluorouracil (5-FU) (Drug)
Cohort2: JS007+JS001+Irinotecan Liposome Injection+5-FU/LV
Participants with unresectable locally advanced or metastatic pancreatic cancer who had previously failed at least first line gemcitabine-based system therapy will receive JS007 and JS001 combined with chemotherapy (irinotecan liposome injection+5-FU/LV) until the treatment termination event specified in the protocol occurs.
干预措施: Leucovorin (LV) (Drug)
Cohort3: JS015+JS001+Irinotecan Liposome Injection+5-FU/LV
Participants with unresectable locally advanced or metastatic pancreatic cancer who had previously failed at least first line gemcitabine-based system therapy will receive JS015 and JS001 combined with chemotherapy (irinotecan liposome injection+5-FU/LV) until the treatment termination event specified in the protocol occurs.
干预措施: JS001 (Drug)
Cohort3: JS015+JS001+Irinotecan Liposome Injection+5-FU/LV
Participants with unresectable locally advanced or metastatic pancreatic cancer who had previously failed at least first line gemcitabine-based system therapy will receive JS015 and JS001 combined with chemotherapy (irinotecan liposome injection+5-FU/LV) until the treatment termination event specified in the protocol occurs.
干预措施: JS015 (Drug)
Cohort3: JS015+JS001+Irinotecan Liposome Injection+5-FU/LV
Participants with unresectable locally advanced or metastatic pancreatic cancer who had previously failed at least first line gemcitabine-based system therapy will receive JS015 and JS001 combined with chemotherapy (irinotecan liposome injection+5-FU/LV) until the treatment termination event specified in the protocol occurs.
干预措施: Irinotecan Liposome Injection (Drug)
Cohort3: JS015+JS001+Irinotecan Liposome Injection+5-FU/LV
Participants with unresectable locally advanced or metastatic pancreatic cancer who had previously failed at least first line gemcitabine-based system therapy will receive JS015 and JS001 combined with chemotherapy (irinotecan liposome injection+5-FU/LV) until the treatment termination event specified in the protocol occurs.
干预措施: 5-Fluorouracil (5-FU) (Drug)
Cohort3: JS015+JS001+Irinotecan Liposome Injection+5-FU/LV
Participants with unresectable locally advanced or metastatic pancreatic cancer who had previously failed at least first line gemcitabine-based system therapy will receive JS015 and JS001 combined with chemotherapy (irinotecan liposome injection+5-FU/LV) until the treatment termination event specified in the protocol occurs.
干预措施: Leucovorin (LV) (Drug)
Cohort4: JS004+JS001+Nab-Paclitaxel+Gemcitabine
Participants with previously untreated systemic pancreatic cancer with unresectable locally advanced or metastatic pancreatic cancer will receive JS004 and JS001 combined with chemotherapy (nab-paclitaxel+gemcitabine) until the treatment termination event specified in the protocol occurs.
干预措施: JS001 (Drug)
Cohort4: JS004+JS001+Nab-Paclitaxel+Gemcitabine
Participants with previously untreated systemic pancreatic cancer with unresectable locally advanced or metastatic pancreatic cancer will receive JS004 and JS001 combined with chemotherapy (nab-paclitaxel+gemcitabine) until the treatment termination event specified in the protocol occurs.
干预措施: JS004 (Drug)
Cohort4: JS004+JS001+Nab-Paclitaxel+Gemcitabine
Participants with previously untreated systemic pancreatic cancer with unresectable locally advanced or metastatic pancreatic cancer will receive JS004 and JS001 combined with chemotherapy (nab-paclitaxel+gemcitabine) until the treatment termination event specified in the protocol occurs.
干预措施: Nab paclitaxel (Drug)
Cohort4: JS004+JS001+Nab-Paclitaxel+Gemcitabine
Participants with previously untreated systemic pancreatic cancer with unresectable locally advanced or metastatic pancreatic cancer will receive JS004 and JS001 combined with chemotherapy (nab-paclitaxel+gemcitabine) until the treatment termination event specified in the protocol occurs.
干预措施: Gemcitabine (Drug)
Cohort5: JS007+JS001+Nab-Paclitaxel+Gemcitabine
Participants with previously untreated systemic pancreatic cancer with unresectable locally advanced or metastatic pancreatic cancer will receive JS007 and JS001 combined with chemotherapy (nab-paclitaxel+gemcitabine) until the treatment termination event specified in the protocol occurs.
干预措施: JS001 (Drug)
Cohort5: JS007+JS001+Nab-Paclitaxel+Gemcitabine
Participants with previously untreated systemic pancreatic cancer with unresectable locally advanced or metastatic pancreatic cancer will receive JS007 and JS001 combined with chemotherapy (nab-paclitaxel+gemcitabine) until the treatment termination event specified in the protocol occurs.
干预措施: JS007 (Drug)
Cohort5: JS007+JS001+Nab-Paclitaxel+Gemcitabine
Participants with previously untreated systemic pancreatic cancer with unresectable locally advanced or metastatic pancreatic cancer will receive JS007 and JS001 combined with chemotherapy (nab-paclitaxel+gemcitabine) until the treatment termination event specified in the protocol occurs.
干预措施: Nab paclitaxel (Drug)
Cohort5: JS007+JS001+Nab-Paclitaxel+Gemcitabine
Participants with previously untreated systemic pancreatic cancer with unresectable locally advanced or metastatic pancreatic cancer will receive JS007 and JS001 combined with chemotherapy (nab-paclitaxel+gemcitabine) until the treatment termination event specified in the protocol occurs.
干预措施: Gemcitabine (Drug)
Cohort6: JS015+JS001+ Nab-Paclitaxel+Gemcitabine
Participants with previously untreated systemic pancreatic cancer with unresectable locally advanced or metastatic pancreatic cancer will receive JS015 and JS001 combined with chemotherapy (nab-paclitaxel+gemcitabine) until the treatment termination event specified in the protocol occurs.
干预措施: JS001 (Drug)
Cohort6: JS015+JS001+ Nab-Paclitaxel+Gemcitabine
Participants with previously untreated systemic pancreatic cancer with unresectable locally advanced or metastatic pancreatic cancer will receive JS015 and JS001 combined with chemotherapy (nab-paclitaxel+gemcitabine) until the treatment termination event specified in the protocol occurs.
干预措施: JS015 (Drug)
Cohort6: JS015+JS001+ Nab-Paclitaxel+Gemcitabine
Participants with previously untreated systemic pancreatic cancer with unresectable locally advanced or metastatic pancreatic cancer will receive JS015 and JS001 combined with chemotherapy (nab-paclitaxel+gemcitabine) until the treatment termination event specified in the protocol occurs.
干预措施: Nab paclitaxel (Drug)
Cohort6: JS015+JS001+ Nab-Paclitaxel+Gemcitabine
Participants with previously untreated systemic pancreatic cancer with unresectable locally advanced or metastatic pancreatic cancer will receive JS015 and JS001 combined with chemotherapy (nab-paclitaxel+gemcitabine) until the treatment termination event specified in the protocol occurs.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Objective Response Rate (ORR) (phase II)
时间窗: Up to 1 year
ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) based on RECIST 1.1.
Incidence of dose-limiting toxicity (DLT) (phase IB)
时间窗: 21 days after the first dose was administered to each subject
If less than 2 participants developed DLT during the safety observation period (one cycle after the first dose), follow-up first-line D/E/F cohort exploration should be considered. Otherwise, it is up to the investigator to decide the next research plan.
次要结局
- Objective Response Rate (ORR) (phase IB)(Up to 1 year)
- Disease control rate (DCR)(Up to 1 year)
- Duration of Response (DOR)(Up to 1 year)
- Progression free survival (PFS)(Up to 2 years)
- Overall Survival (OS)(Up to 2 years)
- Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment(90 days after the last administration)