A Study to Evaluate DJI136, a DLL3-targeted CAR-T Therapy

Official title

A Phase I/II Open-label Study of DJI136, a DLL3-targeted CAR-T Therapy, in Adult Patients With ES-SCLC

Overview

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.

Detailed description

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.

Interventions

• Drug DJI136
  DLL3 targeted CAR-T therapy administered by intravenous (i.v.) infusion.

Primary outcome measures

• All study parts: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) [Time frame: Up to approximately 2 years]
• All study parts: Incidence and severity of dose-limiting toxicities (DLTs) [Time frame: 28 days]
• Phase II Group A: Overall response rate (ORR) as per RECIST v1.1 [Time frame: Up to approximately 2 years]

Secondary outcome measures (9)

• Phase I Part A and Phase II exploratory group: Overall response rate (ORR) as per RECIST v1.1 [Time frame: Up to approximately 2 years]
• Phase I Part A and Phase II: Disease control rate (DCR) as per RECIST v1.1 [Time frame: Up to approximately 2 years]
• Phase I Part A and Phase II: Duration of response (DOR) as per RECIST v1.1 [Time frame: Up to approximately 2 years]
• Phase I Part A and Phase II: Progression free survival (PFS) as per RECIST v1.1 [Time frame: Up to approximately 2 years]
• Phase I Part A and Phase II: Maximum observed concentration (Cmax) in peripheral blood [Time frame: 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 [Time frame: 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) [Time frame: From pre-dose up to Day 720 (Month 24)]
• Phase I Part A and Phase II: Last observed quantifiable concentration (Clast) in peripheral blood [Time frame: 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 [Time frame: From pre-dose up to Day 720 (Month 24)]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 3 centers

• University of Kentucky — Lexington
• MD Anderson Cancer Center — Houston
• Fred Hutchinson Cancer Center — Seattle

Singapore · 1 center

• Novartis Investigative Site — Singapore

Identifiers

NCT: NCT07564401 · CDJI136A12101 · 2025-523276-23

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗