CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

* 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 1.
* 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.

Exclusion Criteria:

* 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.

主要终点：All study parts: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) · Number of participants with AEs and SAEs, including changes in vital signs, electrocardiograms (ECGs) and laboratory values qualifying and reported as AEs. · Up to approximately 2 years；All study parts: Incidence and severity of dose-limiting toxicities (DLTs) · 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. · 28 days；Phase II Group A: Overall response rate (ORR) as per RECIST v1.1 · 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). · Up to approximately 2 years
次要终点：Phase I Part A and Phase II exploratory group: Overall response rate (ORR) as per RECIST v1.1；Phase I Part A and Phase II: Disease control rate (DCR) as per RECIST v1.1；Phase I Part A and Phase II: Duration of response (DOR) as per RECIST v1.1；Phase I Part A and Phase II: Progression free survival (PFS) as per RECIST v1.1；Phase I Part A and Phase II: Maximum observed concentration (Cmax) in peripheral blood；Phase I Part A and Phase II: Time to reach maximum observed concentration (Tmax) in peripheral blood；Phase I Part A and Phase II: Area under the peripheral blood concentration-time curve (AUC)；Phase I Part A and Phase II: Last observed quantifiable concentration (Clast) in peripheral blood

• Phase I · EXPERIMENTAL · Dose escalation with DJI136
• Phase II · EXPERIMENTAL · Treatment at the recommended dose(s) of DJI136 as identified in Phase I.

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.