NCT04404595进行中（未招募）1 期
Open-label, Multicenter, Phase 1b/2 Clinical Trial to Evaluate the Safety and Efficacy of Autologous Anti-claudin 18.2 Chimeric Antigen Receptor T-cell Therapy in Subjects with Advanced Gastric, Pancreatic, or Other Specified Digestive System Cancers
CARsgen Therapeutics Co., Ltd.16 个研究点 分布在 2 个国家目标入组 110 人开始时间: 2020年10月23日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 110
- 试验地点
- 16
- 主要终点
- Phase 1b (Cohort A): Evaluate the safety and tolerability of CAR-CLDN18.2 T-cell therapy (CT041) in subjects with specified advanced digestive system cancers (STAD, PAAD, or BTC).
研究概览
简要总结
A Phase 1b/2, open label, multi-center, clinical study of Chimeric Antigen Receptor T Cells (CAR-T) targeting claudin18.2 in patients with advanced gastric, pancreatic or other specified digestive system cancers
详细描述
This is an open label, multi-center, Phase 1b/2 clinical trial to evaluate the safety and efficacy of autologous claudin18.2 chimeric antigen receptor T-cell therapy in patients with advanced gastric, pancreatic or other specified digestive system cancers.
Following consent, patients must have tumor tissue evaluated by CLDN18.2 IHC assay. Patients meeting all eligibility criteria will undergo a leukapheresis procedure to collect autologous mononuclear cells for manufacture of investigational drug product (CT041). Following manufacture of the drug product, subjects will receive preconditioning prior to CT041 infusion. All subjects will be asked to continue to undergo long-term gene safety follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 76 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients are eligible for screening for potential inclusion in the study (* indicates inclusion criteria at Baseline (for subjects to be eligible for preconditioning)):
- •Voluntarily signed the ICF;
- •Age ≥ 18 and < 76 years with pathologically/histologically confirmed diagnosis of adenocarcinoma of the stomach or gastroesophageal junction, referred to collectively as STAD, or pancreatic adenocarcinoma (PAAD);or biliary tract cancers (BTCs, including intrahepatic/extrahepatic cholangiocarcinoma and gallbladder cancer but not ampullary carcinoma);
- •Must have CLDN18.2-positive tumor expression as determined by the CLDN18.2 IHC assay;
- •Estimated life expectancy > 4 months*;
- •Failed or been intolerant of prior lines of systemic therapy:
- •For screening:
- •Leukapheresis can be performed for subjects with STAD who have progressed or were intolerant of at least 1 prior line of systemic therapy, or,
- •Leukapheresis can be performed for subjects with PAAD who are receiving first-line treatment, or,
- •Leukapheresis can be performed for subjects with BTC who are receiving first-line treatment.
- •Baseline*:
- •Subjects with STAD who have progressed or were intolerant of at least 2 prior lines of systemic therapy, or,
- •Subjects with PAAD who have progressed or were intolerant of at least 1 prior line of systemic therapy, or,
- •Subjects with BTC who have progressed or were intolerant of at least 1 prior line of systemic therapy. For subjects with CCA with who has FGFR2 fusions or rearrangements, or IDH1-mutant must have received FDA-approved target therapies.
- •At least 1 measurable lesion per RECIST 1.1*;
- •ECOG performance status of 0 or 1*;
- •Sufficient venous access for leukapheresis collection and no other contraindications to leukapheresis;
- •Patients should have adequate CBC counts, renal and hepatic functions*;
- •Women of childbearing age must undergo a serum pregnancy test with negative results before screening and infusion and be willing to use effective and reliable method of contraception*;
- •Men must be willing to use effective and reliable method of contraception for at least 12-months after T-cell infusion*;
- •Sufficient nutritional status.
- •Exclusion Criteria for screening (* indicates exclusion criteria for baseline as well):
- •Pregnant or lactating women*;
- •HIV, active hepatitis C virus (HCV), active hepatitis B virus (HBV), or active syphilis infection;
- •Any active infection requiring systemic treatment*;
- •AEs from previous treatment that have not recovered*;
- •Patients who have clinically significant thyroid dysfunction;
- •Patients allergic to any drugs of the preconditioning regimen, tocilizumab, dimethyl sulfoxide (DMSO), or CT041 CAR-CLDN18.2 T-cell;
- •Patients who have received:
- •prior cellular therapy such as (CAR T, TCR, tumor-infiltrating lymphocytes) within one year.
- •organ transplantation.
- •previous anti-claudin18.2 CAR T-cell therapy, mRNA-based cancer immunotherapy, or bispecific T cell engager.
- •Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression;
- •Patients with heavy tumor burdens;
- •Unstable/active ulcer, anastomotic recurrence with full-thickness tumor infiltration or tumor involving any major vessels, digestive tract bleeding, or recent digestive surgery that may have increased risk of bleeding*;
- •Patients who have a history of esophageal or gastric resection plus current evidence of locally recurrent tumor that involves any major blood vessels or that has evidence of recent bleeding or perforation*;
- •Patients requiring anticoagulant therapy such as warfarin or heparin;
- •Patients requiring long-term antiplatelet therapy;
- •Use of prednisone >/= 10mg daily or other equivalent steroids within 14 days before leukapheresis or preconditioning*;
- •Anticancer treatment within approximately 2 weeks prior to leukapheresis or preconditioning*;
- •Major surgery less than 1 week prior to leukapheresis or 3 weeks prior to preconditioning*;
- •Patients who have clinically significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients*;
- •Inadequate pulmonary function*;
- •Patients known to have active autoimmune diseases;
- •Patients with second malignancies;
- •Patients have significant neurologic disorders;
- •Patients are unable or unwilling to comply with the requirements of clinical trial.
- •Additional exclusion criteria solely for baseline (prior to conditioning regimen):
- •Fever > 38.0°C;
- •Active illness or existing toxicity that would place the subject at undue risk;
- 另有 10 项未显示
排除标准
- 未提供
研究组 & 干预措施
anti-claudin18.2 chimeric antigen receptor T-cell therapy
Experimental
Phase 1b will include two parts, dose escalation phase (Cohort A) followed by a dose expansion phase (Cohort B). Phase 2 (Cohort C) will evaluate the chosen dose in patients with advanced gastric cancer.
干预措施: CT041 (Biological)
结局指标
主要结局
Phase 1b (Cohort A): Evaluate the safety and tolerability of CAR-CLDN18.2 T-cell therapy (CT041) in subjects with specified advanced digestive system cancers (STAD, PAAD, or BTC).
时间窗: up to year 15
Incidence of adverse events (AEs), AEs of special interest (cytokine release syndrome \[CRS\], neurotoxicity, secondary malignancy), serious adverse events (SAEs).
Phase 1b (Cohort A): Identify the recommended Phase 2 dose (RP2D) of CT041 therapy in subjects with advanced STAD, PAAD, or BTC.
时间窗: day 0 - day 28
Incidence of dose-limiting toxicities (DLTs)
Phase 1b (Cohort A): Identify the maximum tolerated dose (MTD) or maximum administered dose (MAD) of CT041 therapy in subjects with STAD, PAAD, or BTC.
时间窗: day 0 - day 28
The highest dose below the dose where the escalation was stopped when the frequency or severity of DLTs exceeds predefined safety criteria.
Phase 1b (Cohort B): Determine the efficacy of CT041 by ORR in subjects with advanced STAD, PAAD, or BTC.
时间窗: up to year 15
Objective response rate by IRC assessment (RECIST v1.1)
Phase 2 (Cohort C): Determine the efficacy of CT041 by ORR in subjects with advanced STAD treated at the RP2D.
时间窗: up to year 15
Objective response rate by IRC assessment (RECIST v1.1)
次要结局
- Phase 1b/2: Objective Response Rate (ORR) per investigator assessment(up to year 15)
- Phase 1b (Cohort A): Duration of Response(up to year 15)
- Phase 1b (Cohort A): Time to Progression(up to year 15)
- Phase 1b (Cohort A): Disease Control Rate(up to year 15)
- Phase 1b (Cohort A): Progression free survival(up to year 15)
- Phase 1b (Cohort B): Evaluate the safety and tolerability of CAR-CLDN18.2 T-cell therapy (CT041) in subjects with specified advanced digestive system cancers (STAD, PAAD, or BTC).(up to year 15)
- Phase 2 (Cohort C): Evaluate the safety and tolerability of CAR-CLDN18.2 T-cell therapy (CT041) in subjects with advanced STAD.(up to year 15)
- Phase 1b(Cohort B)/2: Duration of Response(up to year 15)
- Phase 1b(Cohort B)/2: Time to Progression(up to year 15)
- Phase 1b(Cohort B)/2: Disease Control Rate(up to year 15)
- Phase 1b(Cohort B)/2: Progression free survival(up to year 15)
- Phase 1b/2: Overall survival(up to year 15)
- Phase 1b/2: Utilization of Hospital Resources(Day 0 to 3 months)
- Phase 1b(Cohort B)/2: PK and bio-distribution of CT041(Baseline - month 18)
- Phase 1b(Cohort B)/2: Health-related Quality of Life (HRQoL) in STAD patients (Cohorts B & C)(Baseline - month 18)
- Phase 1b(Cohort B)/2: CLDN18.2 ICH Assay Performance(Baseline - month 18)
- Phase 1b(Cohort B)/2: Cytokine expression level in blood after CT041 infusion(Baseline - week 20)
- Phase 1b (Cohort B)/2: Anti-CT041 drug antibodies(Baseline - month 12)
- Phase 1b (Cohort B)/2: CT041 product characteristics(Baseline - month 18)
- Phase 1b (Cohort B)/2: Concordance analysis(up to year 15)
研究者
研究点 (16)
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相关资讯
CARsgen's Satri-cel Shows Promise in Phase II Trial for Advanced Gastric and GEJ Cancers- CARsgen Therapeutics' satri-cel significantly improved progression-free survival in patients with advanced gastric/gastroesophageal junction cancers.
- The Phase II trial (CT041-ST-01) evaluated satri-cel in patients with Claudin18.2-positive tumors who had failed at least two prior lines of therapy.
- CARsgen plans to submit a New Drug Application to China's NMPA in the first half of 2025, potentially marking the first CAR-T therapy for solid tumors.
- Satri-cel has received Breakthrough Therapy Designation from China's NMPA and RMAT designation from the U.S. FDA, expediting its development and review.last yearFDA Lifts Clinical Holds on CARsgen's CAR-T Therapies for Multiple Myeloma and Gastric/Pancreatic Cancers- The FDA has removed clinical holds on three of CARsgen's CAR-T cell therapies, including zevorcabtagene autoleucel for multiple myeloma.
- The holds were initially placed due to chemistry, manufacturing, and controls (CMC)-related questions following an inspection of CARsgen’s facility.
- Zevor-cel is already approved in China for relapsed/refractory multiple myeloma after at least three prior lines of therapy.
- The lifted holds allow CARsgen to continue clinical trials evaluating satricabtagene autoleucel for gastric/pancreatic cancers and CT071 for multiple myeloma.last yearFDA Lifts Clinical Holds on CARsgen's CAR-T Therapy Trials- The FDA has lifted clinical holds on CARsgen Therapeutics' trials for zevor-cel, satri-cel, and CT071, allowing the resumption of these studies in the US.
- The holds were initiated due to CMC concerns identified during an inspection of CARsgen's manufacturing facility in Durham, North Carolina.
- Zevor-cel targets BCMA for relapsed/refractory multiple myeloma, satri-cel targets claudin 18.2 in solid tumors, and CT071 targets GPRC5D for RRMM and primary plasma cell leukemia.last year