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.
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
80
DLL3 targeted CAR-T therapy administered by intravenous (i.v.) infusion.
University of Kentucky
Lexington, Kentucky, United States
RECRUITINGMD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGFred Hutchinson Cancer Center
Seattle, Washington, United States
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.
Time frame: 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.
Time frame: 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).
Time frame: Up to approximately 2 years
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).
Time frame: 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).
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Novartis Investigative Site
Clayton, Victoria, Australia
RECRUITINGNovartis Investigative Site
Singapore, Singapore
RECRUITINGNovartis Investigative Site
Seoul, South Korea
RECRUITINGTime frame: 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.
Time frame: 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.
Time frame: 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.
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
Cellular kinetics parameters will be determined by non-compartmental method(s) based on DJI136 CAR transgene concentrations 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)
Cellular kinetics parameters will be determined by non-compartmental method(s) based on DJI136 CAR transgene concentrations in peripheral blood.
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
Cellular kinetics parameters will be determined by non-compartmental method(s) based on DJI136 CAR transgene concentrations 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
Cellular kinetics parameters will be determined by non-compartmental method(s) based on DJI136 CAR transgene concentrations in peripheral blood.
Time frame: From pre-dose up to Day 720 (Month 24)