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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Extensive-stage Small Cell Lung Cancer (ES-SCLC)
• Intervention / Treatment: Drug: 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.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Study Locations

• Singapore
  • Singapore, Singapore, 168583
    • Recruiting
    • Novartis Investigative Site
• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Contact: Zheng Zhang; Phone Number: 713-792-0007; Email: Zzhang11@mdanderson.org
      • Principal Investigator: Bingnan Zhang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I; Dose escalation with DJI136	Drug: DJI136; DLL3 targeted CAR-T therapy administered by intravenous (i.v.) infusion.
Experimental: Phase II; Treatment at the recommended dose(s) of DJI136 as identified in Phase I.	Drug: DJI136; DLL3 targeted CAR-T therapy administered by intravenous (i.v.) infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I Part A and Phase II exploratory group: 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
Phase I Part A and Phase II: Disease control rate (DCR) 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). DCR per RECIST v1.1 is defined as the proportion of patients with a confirmed best overall response of CR, PR, or Stable disease (SD).	Up to approximately 2 years
Phase I Part A and Phase II: Duration of response (DOR) 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). DOR is defined as the time from the date of the first documented response (CR or PR) to the date of the first documented progression according to RECIST v1.1 or death due to underlying cancer.	Up to approximately 2 years
Phase I Part A and Phase II: Progression free survival (PFS) 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). PFS is defined as the time from the date of DJI136 infusion to the date of the first documented progression according to RECIST v1.1, or death due to any cause.	Up to approximately 2 years
Phase I Part A and Phase II: Maximum observed concentration (Cmax) in peripheral blood	Cellular kinetics parameters will be determined by non-compartmental method(s) based on DJI136 chimeric antigen receptor (CAR) transgene concentrations 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	Cellular kinetics parameters will be determined by non-compartmental method(s) based on DJI136 CAR transgene concentrations 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)	Cellular kinetics parameters will be determined by non-compartmental method(s) based on DJI136 CAR transgene concentrations in peripheral blood.	From pre-dose up to Day 720 (Month 24)
Phase I Part A and Phase II: Last observed quantifiable concentration (Clast) in peripheral blood	Cellular kinetics parameters will be determined by non-compartmental method(s) based on DJI136 CAR transgene concentrations 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	Cellular kinetics parameters will be determined by non-compartmental method(s) based on DJI136 CAR transgene concentrations in peripheral blood.	From pre-dose up to Day 720 (Month 24)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): May 14, 2026
• Primary Completion (Estimated): March 3, 2031
• Study Completion (Estimated): March 3, 2031

Study Registration Dates

• First Submitted: April 27, 2026
• First Submitted That Met QC Criteria: April 27, 2026
• First Posted (Actual): May 4, 2026

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Small cell lung cancer; ES-SCLC; SCLC; DLL3; Extensive-stage small cell lung cancer; Delta-like ligand 3; Chimeric antigen receptor (CAR)-T cell therapy; DJI136
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Small Cell Lung Carcinoma
• Other Study ID Numbers: CDJI136A12101; 2025-523276-23 (Other Identifier: EU CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No