A Study to Investigate LYL797 in Adults With Solid Tumors

Phase 1

Active, not recruiting

Conditions: Triple Negative Breast Cancer
TNBC - Triple-Negative Breast Cancer
Non-small Cell Lung Cancer
Non Small Cell Lung Cancer
Non Small Cell Lung Cancer Metastatic
Non-Small Cell Carcinoma of Lung, TNM Stage 4
Advanced Breast Cancer
Advanced Lung Carcinoma
NSCLC
NSCLC, Recurrent

Brief Summary: 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) or non-small cell lung cancer (NSCLC). The first part of the study will determine the safe dose for the next part of the study, and will enroll TNBC and NSCLC patients. The second part of the study will test that dose in additional TNBC and NSCLC patients.

Detailed Description: This Phase 1, single-arm, open-label, multi-center, dose-escalation and -expansion study will evaluate the safety and tolerability of LYL797, ROR1-targeting CAR T cells, in adults with relapsed and/or refractory ROR1+ triple negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC). The dose-escalation phase includes TNBC and NSCLC patients, and will investigate 4 dose levels to determine the recommended Phase 2 dose (RP2D). The dose-expansion phase will enroll both TNBC and NSCLC patients at the RP2D.

Recruitment & Eligibility

Inclusion Criteria

≥ 18 years of age at time of informed consent
Histologically confirmed TNBC or NSCLC that is relapsed or refractory, metastatic or locally advanced and unresectable that is ROR1+ by central laboratory immunohistochemistry (IHC)
Measurable disease including a target lesion and an additional lesion for biopsy
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Adequate organ and marrow function
Women of childbearing potential must have a negative pregnancy test at screening
All participants must agree to practice highly effective methods of contraception

Exclusion Criteria

Prior treatment with any adoptive T-cell therapy or anti-ROR1 therapy
Prior solid organ transplantation
Active, untreated brain metastasis or leptomeningeal disease; stable, treated brain involvement by disease is allowed
Untreated or active infection at the time of screening or leukapheresis
HIV-positive, HTLV-1-positive, active acute or chronic HBV or HCV, or active tuberculosis
Impaired cardiac function or clinically significant cardiac disease
Uncontrolled pleural or pericardial effusion
Systemic corticosteroids or other immunosuppressive medications within 14 days of leukapheresis
Required chronic anticoagulation, such as warfarin, low molecular weight heparin, or Factor Xa inhibitors
Pregnant or lactating/nursing women

Arm && Interventions

Group	Intervention	Description
Experimental LYL797	LYL797	ROR1-targeted CAR T cells

Primary Outcome Measures

Name	Time	Method
Evaluate incidence of dose-limiting toxicities (DLTs)	Up to 28 days	Incidence of dose-limiting toxicities (DLTs)
Evaluate incidence of treatment-emergent adverse events (TEAEs)	Up to 2 years	Incidence of treatment-emergent adverse events (TEAEs)
Evaluate severity of treatment-emergent adverse events (TEAEs)	Up to 2 years	Severity of treatment-emergent adverse events (TEAEs)
Determine recommended Phase 2 Dose (RP2D)	Up to 2 years	Dose-escalation phase to determine the recommended Phase 2 dose

Secondary Outcome Measures

Name	Time	Method
Evaluate overall survival (OS)	Up to 2 years	Overall Survival (OS)
Evaluate anti-tumor activity of LYL797 based on overall response rate (ORR) by RECIST, version 1.1	Up to 2 years	Overall response rate (ORR) by RECIST, version 1.1
Evaluate duration of response (DOR)	Up to 2 years	Duration of response (DOR)
Evaluate progression-free survival (PFS)	Up to 2 years	Progression-free survival (PFS)
Evaluate maximum concentration of LYL797 (Cmax) of LYL797 in peripheral blood (PB) samples	Up to 2 years	Maximum concentration of LYL797 (Cmax)
Evaluate time to Cmax (Tmax) of LYL797 in peripheral blood (PB) samples	Up to 2 years	Time to Cmax (Tmax)
Evaluate area under the concentration-time curve (AUC) of LYL797 in the peripheral blood (PB)	Up to 2 years	Area under the concentration-time curve (AUC)
Evaluate Persistence of LYL797 CAR T cells in peripheral blood samples	Up to 2 years	Time to last detectable LYL797, Tlast

Locations (16): Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
University of California, Los Angeles
🇺🇸
Santa Monica, California, United States
Yale New Haven Hospital
🇺🇸
New Haven, Connecticut, United States
Georgetown University
🇺🇸
Washington, District of Columbia, United States
University of Miami
🇺🇸
Miami, Florida, United States
University of Chicago
🇺🇸
Chicago, Illinois, United States
Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
Montefiore Medical Center
🇺🇸
Bronx, New York, United States
Sidney Kimmel Cancer Center, Jefferson University Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States
Sarah Cannon Research Institute and Tennessee Oncology
🇺🇸
Nashville, Tennessee, United States
University of Oklahoma
🇺🇸
Oklahoma City, Oklahoma, United States
Oregon Health and Science University Hospital
🇺🇸
Portland, Oregon, United States
MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Fred Hutchinson Cancer Research Center
🇺🇸
Seattle, Washington, United States
Froedtert Hospital, Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States