A Phase I/II Open-label Study of DJI136, a DLL3-targeted CAR-T Therapy, in Adult Patients With ES-SCLC
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 6
- 主要终点
- All study parts: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
研究概览
简要总结
This is a Phase I/II, open-label, non-randomized, multi-center study in patients with extensive-stage small cell lung cancer (ES-SCLC) to determine the recommended dose(s) (RD) and to evaluate the safety, tolerability and preliminary efficacy of DJI136.
详细描述
This is a first in human (FIH) Phase I/II, multicenter, open-label study of DJI136 (a CAR-T therapy). The study will start with a Phase I dose escalation with two parts: Part A where patients with ES-SCLC that experience disease progression after one or more chemotherapy regimens according to the standard of care (SOC) will be treated with DJI136. The second part is an optional exploratory component.
The Phase II may follow with two groups. In Group A, ES-SCLC patients who have disease progression after one standard chemotherapy regimen according to the SOC may receive the dose of DJI136 identified in Phase I to assess the preliminary anti-tumor activity of DJI136. The second group is an optional exploratory component.
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
- •Phase I: Patients with ES-SCLC and disease progression after one or more chemotherapy regimens (that included a platinum-based doublet chemotherapy in combination with a PD-L1 inhibitor) according to the local SOC (2L+), unless the patient was ineligible to receive such therapies or was not a candidate for any available standard therapy, according to the investigator's judgement. Prior DLL3 (Delta-like ligand 3) targeted therapy is allowed.
- •Phase II: Patients with ES-SCLC who have received a platinum-based doublet chemotherapy in combination with a PD-L1 inhibitor according to local standard of care, unless the patient was ineligible to receive such therapies or was not a candidate for any available standard therapy, as determined by the investigator's judgment. Prior DLL-3 targeted therapy is not allowed.
- •Male or female patients must be ≥ 18 years of age.
- •Histologically or cytologically confirmed small cell lung cancer (SCLC).
- •At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Patients must have an archival tumor tissue available, collected within 6 months prior to screening. If an archival tumor sample, collected within 6 months prior to screening, is not available, patients must be willing to undergo a new tumor biopsy at screening; , however this specimen need not be collected prior to scheduling leukapheresis. If a new biopsy is not medically feasible, exceptions may be considered after documented discussion with the Novartis medical monitor.
- •Patient must be deemed suitable by the investigator to undergo the lymphodepletion (LD) regimen.
- •Patient must have an apheresis product of non-mobilized cells accepted for manufacturing.
排除标准
- •Prior administration of a genetically modified cellular product, including prior DLL3-targeted CAR-T cell therapy.
- •Unstable or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. Stable brain metastases may participate provided they meet the specific criteria.
- •Uncontrolled seizure disorder.
- •Clinically significant active infections, including Hepatitis B/C and Human Immunodeficiency Virus (HIV).
- •Has a known additional malignancy that is progressing or requires active treatment, with specific exceptions as defined in the study protocol.
- •History of prior solid organ transplant or allogenic hematopoietic cell transplant
- •Other significant pulmonary, cardiac, hepatic, renal or neurologic disease, parameters for which are defined in the study protocol.
- •Pregnant or nursing women.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Phase I
Dose escalation with DJI136
干预措施: DJI136 (Drug)
Phase II
Treatment at the recommended dose(s) of DJI136 as identified in Phase I.
干预措施: DJI136 (Drug)
结局指标
主要结局
All study parts: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
时间窗: Up to approximately 2 years
Number of participants with AEs and SAEs, including changes in vital signs, electrocardiograms (ECGs) and laboratory values qualifying and reported as AEs.
All study parts: Incidence and severity of dose-limiting toxicities (DLTs)
时间窗: 28 days
Number of participants with DLTs. A DLT is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher assessed as unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurs within the first 28 days after DJI136 infusion and meets the criteria defined in the protocol. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
Phase II Group A: Overall response rate (ORR) as per RECIST v1.1
时间窗: Up to approximately 2 years
Tumor response assessed by the investigator based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). ORR per RECIST v1.1 is defined as the proportion of patients with a confirmed best overall response of Complete response (CR) or Partial response (PR).
次要结局
- Phase I Part A and Phase II exploratory group: Overall response rate (ORR) as per RECIST v1.1(Up to approximately 2 years)
- Phase I Part A and Phase II: Disease control rate (DCR) as per RECIST v1.1(Up to approximately 2 years)
- Phase I Part A and Phase II: Duration of response (DOR) as per RECIST v1.1(Up to approximately 2 years)
- Phase I Part A and Phase II: Progression free survival (PFS) as per RECIST v1.1(Up to approximately 2 years)
- Phase I Part A and Phase II: Maximum observed concentration (Cmax) in peripheral blood(From pre-dose up to Day 720 (Month 24))
- Phase I Part A and Phase II: Time to reach maximum observed concentration (Tmax) in peripheral blood(From pre-dose up to Day 720 (Month 24))
- Phase I Part A and Phase II: Area under the peripheral blood concentration-time curve (AUC)(From pre-dose up to Day 720 (Month 24))
- Phase I Part A and Phase II: Last observed quantifiable concentration (Clast) in peripheral blood(From pre-dose up to Day 720 (Month 24))
- Phase I Part A and Phase II: Time of last observed quantifiable concentration (Tlast) in peripheral blood(From pre-dose up to Day 720 (Month 24))