This study will evaluate the safety and tolerability of LYL797, a ROR1-targeted CAR T-cell therapy, in patients with ROR1+ relapsed or refractory triple negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), platinum-resistant epithelial ovarian cancer/ fallopian tube cancer/ primary peritoneal cancer (Ovarian cancer), or Endometrial cancer. The first part of the study will determine the safe dose for the next part of the study, and will enroll patients with TNBC, NSCLC, Ovarian or Endometrial cancer. The second part of the study will test that dose in additional patients with TNBC, NSCLC, Ovarian or Endometrial cancer.
This Phase 1, single-arm, open-label, multi-center, dose-escalation and expansion study will evaluate the safety and tolerability of LYL797, ROR1- targeted CAR T cells, in adults with relapsed and/or refractory ROR1+ triple negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), Ovarian cancer, or endometrial cancer. The dose-escalation phase includes patients with TNBC, NSCLC, Ovarian, or Endometrial cancer, and will investigate multiple dose levels to identify the recommended Phase 2 dose (RP2D). The dose-expansion phase will enroll patients with TNBC, NSCLC, Ovarian, or Endometrial cancer at the RP2D.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
57
LYL797 is an autologous, genetically (Gen-R™) and epigenetically (Epi-R™) reprogrammed ROR1-targeted chimeric antigen receptor (CAR) T-cell therapy
Mayo Clinic
Scottsdale, Arizona, United States
University of California, Los Angeles
Santa Monica, California, United States
Yale New Haven Hospital
New Haven, Connecticut, United States
Georgetown University
Washington D.C., District of Columbia, United States
Mayo Clinic
Jacksonville, Florida, United States
University of Miami
Miami, Florida, United States
University of Chicago
Chicago, Illinois, United States
Karmanos Cancer Institute
Detroit, Michigan, United States
Mayo Clinic
Rochester, Minnesota, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
...and 8 more locations
Evaluate incidence of dose-limiting toxicities (DLTs)
Incidence of dose-limiting toxicities (DLTs)
Time frame: Up to 28 days
Evaluate incidence of treatment-emergent adverse events (TEAEs)
Incidence of treatment-emergent adverse events (TEAEs)
Time frame: Up to 2 years
Evaluate severity of treatment-emergent adverse events (TEAEs)
Severity of treatment-emergent adverse events (TEAEs)
Time frame: Up to 2 years
Determine recommended Phase 2 Dose (RP2D)
Dose-escalation phase to determine the recommended Phase 2 dose
Time frame: Up to 2 years
Evaluate anti-tumor activity of LYL797 based on overall response rate (ORR) by RECIST, version 1.1
Overall response rate (ORR) by RECIST, version 1.1
Time frame: Up to 2 years
Evaluate duration of response (DOR)
Duration of response (DOR)
Time frame: Up to 2 years
Evaluate progression-free survival (PFS)
Progression-free survival (PFS)
Time frame: Up to 2 years
Evaluate overall survival (OS)
Overall Survival (OS)
Time frame: Up to 2 years
Evaluate maximum concentration of LYL797 (Cmax) of LYL797 in peripheral blood (PB) samples
Maximum concentration of LYL797 (Cmax)
Time frame: Up to 2 years
Evaluate time to Cmax (Tmax) of LYL797 in peripheral blood (PB) samples
Time to Cmax (Tmax)
Time frame: Up to 2 years
Evaluate area under the concentration-time curve (AUC) of LYL797 in the peripheral blood (PB)
Area under the concentration-time curve (AUC)
Time frame: Up to 2 years
Evaluate Persistence of LYL797 CAR T cells in peripheral blood samples
Time to last detectable LYL797, Tlast
Time frame: Up to 2 years
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