A Study to Investigate LYL797 in Adults With Solid Tumors

Non-small Cell Lung Cancer Clinical Trial

Official title:

A Phase 1 Study to Assess the Safety and Efficacy of LYL797, ROR1-Targeting CAR T Cells, in Adults With Relapsed and/or Refractory Solid-Tumor Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05274451
• Other study ID #: LYL797-101
• Status: Recruiting
• Phase: Phase 1
• Start date: March 29, 2022
• Est. completion date: September 2026

Study information

• Verified date: February 2024
• Source: Lyell Immunopharma, Inc.
• Contact: Jackie Walling, MD, PhD
• Phone: 888-707-7917
• Email: clinicaltrials[@]lyell.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 54
• Est. completion date: September 2026
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Advanced Lung Carcinoma
• Breast Neoplasms
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer
• Non Small Cell Lung Cancer Metastatic
• Non-Small Cell Carcinoma of Lung, TNM Stage 4
• Non-small Cell Lung Cancer
• NSCLC
• NSCLC Stage IV
• NSCLC, Recurrent
• Recurrence
• Recurrent Breast Cancer
• Recurrent NSCLC
• Relapse/Recurrence
• Relapsed Cancer
• TNBC - Triple-Negative Breast Cancer
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Biological:
• LYL797
LYL797 is an autologous, genetically (Gen-R™) and epigenetically (Epi-R™) reprogrammed ROR1-targeted chimeric antigen receptor (CAR) T-cell therapy

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Lyell Immunopharma, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate incidence of dose-limiting toxicities (DLTs)	Incidence of dose-limiting toxicities (DLTs)	Up to 2 years
Primary	Evaluate incidence of treatment-emergent adverse events (TEAEs)	Incidence of treatment-emergent adverse events (TEAEs)	Up to 2 years
Primary	Evaluate severity of treatment-emergent adverse events (TEAEs)	Severity of treatment-emergent adverse events (TEAEs)	Up to 2 years
Primary	Determine recommended Phase 2 Dose (RP2D)	Dose-escalation phase to determine the recommended Phase 2 dose	Up to 2 years
Secondary	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	Up to 2 years
Secondary	Evaluate anti-tumor activity of LYL797 based on complete response (CR) rate by RECIST, version 1.1	Complete response (CR) rate by RECIST, version 1.1	Up to 2 years
Secondary	Evaluate duration of response (DOR)	Duration of response (DOR)	Up to 2 years
Secondary	Evaluate progression-free survival (PFS)	Progression-free survival (PFS)	Up to 2 years
Secondary	Evaluate overall survival (OS)	Overall survival (OS)	Up to 2 years
Secondary	Evaluate maximum concentration of LYL797 (Cmax) of LYL797 in peripheral blood (PB) samples	Maximum concentration of LYL797 (Cmax)	Up to 2 years
Secondary	Evaluate time to Cmax (Tmax) of LYL797 in peripheral blood (PB) samples	Time to Cmax (Tmax)	Up to 2 years
Secondary	Evaluate area under the concentration-time curve (AUC) of LYL797 in the peripheral blood (PB)	Area under the concentration-time curve (AUC)	Up to 2 years
Secondary	Evaluate Persistence of LYL797 CAR T cells in peripheral blood samples	Persistence of LYL797 in PB	Up to 2 years