A Study to Investigate LYL845 in Adults With Solid Tumors

NCT ID: NCT05573035

Last Updated: 2025-07-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-19
• Study Completion Date: 2025-01-09

Brief Summary

This is an open-label, multi-center, dose-escalation study with expansion cohorts, designed to evaluate the safety and anti-tumor activity of LYL845, an epigenetically reprogrammed tumor infiltrating lymphocyte (TIL) therapy, in participants with relapsed or refractory (R/R) metastatic or locally advanced melanoma, non-small cell lung cancer (NSCLC), and colorectal cancer (CRC).

Detailed Description

This is an open-label, multi-center, dose-escalation study with expansion cohorts, designed to evaluate the safety and anti-tumor activity of LYL845, an epigenetically reprogrammed tumor infiltrating lymphocyte (TIL) therapy, in participants with relapsed or refractory (R/R) metastatic or locally advanced melanoma, non-small cell lung cancer (NSCLC), and colorectal cancer (CRC). During the dose-escalation phase of the study (Part A), participants with melanoma will be enrolled. Once a safe recommended Phase 2 dose range (RP2DR) has been established in Part A, enrollment will be expanded (Part B) to include additional participants with melanoma, NSCLC and CRC.

Conditions

Melanoma; Non-small Cell Lung Cancer; Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental LYL845

Epigenetically reprogrammed tumor infiltrating lymphocyte (TIL) therapy

Group Type: EXPERIMENTAL

LYL845

Intervention Type: BIOLOGICAL

LYL845 is an autologous tumor infiltrating lymphocyte (TIL) enhanced via Epi-R, a proprietary epigenetic reprogramming technology

Interventions

LYL845

LYL845 is an autologous tumor infiltrating lymphocyte (TIL) enhanced via Epi-R, a proprietary epigenetic reprogramming technology

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years up to ≤ 75 years at the time of informed consent
• Confirmed diagnosis of melanoma, non-small cell lung cancer (NSCLC), or colorectal cancer (CRC) that is metastatic or locally advanced or unresectable and is relapsed and/or refractory (R/R) after standard therapy for each tumor histology
• Participants must have received prior systemic treatment for their metastatic disease or locally advanced disease based on tumor type as follows:
• Melanoma: participants with disease progression following an immune checkpoint inhibitor (CPI)
• NSCLC: participants with disease progression following at least 1 approved systemic therapy, including an immune CPI-containing regimen for appropriate patients or an approved targeted therapy for known molecular abnormalities if applicable to their disease
• CRC: participants with disease progression following at least 1 line of therapy, including a fluoropyrimidine with oxaliplatin or irinotecan. Microsatellite instability (MSI) high/mismatch repair deficient (dMMR) CRC participants must have disease progression following systemic therapy with immune CPIs.
• Measurable disease including at least 1 lesion that is safely resectable AND a target lesion to measure response and an additional lesion for biopsy
• Eastern Cooperative Oncology Group (ECOG) performance status of 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
• Fully recovered from toxicity from prior systemic anticancer therapy

Exclusion Criteria

• Prior treatment with adoptive cellular therapy
• Prior solid organ transplantation
• Central nervous system (CNS) involvement of disease that is extensive, symptomatic or untreated, or patients with leptomeningeal disease
• Uncontrolled or symptomatic pleural effusion or ascites
• Untreated or active systemic infection
• Active autoimmune disease requiring treatment or primary immunodeficiency syndrome
• Systemic corticosteroids at a dose of >10 mg of prednisone or equivalent per day
• Other primary malignancy within 3 years prior to enrollment
• Impaired cardiac function or clinically significant cardiovascular disease
• Required chronic anticoagulation, such as warfarin, low molecular weight heparin, or Factor Xa inhibitors
• Pregnant or nursing (lactating) women

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lyell Immunopharma, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UC Davis Coomprehensive Cancer Center

Sacramento, California, United States

UCLA Medical Center

Santa Monica, California, United States

Stanford University

Stanford, California, United States

Yale Cancer Center, Yale University

New Haven, Connecticut, United States

Georgetown University

Washington D.C., District of Columbia, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Mayo Clinic Comprehensive Cancer Center

Rochester, Minnesota, United States

Hackensack Meridian Health Inc

Hackensack, New Jersey, United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Duke University Medical Center

Durham, North Carolina, United States

Ohio State University Medical Center

Columbus, Ohio, United States

Oregon Health Sciences University

Portland, Oregon, United States

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, United States

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Countries

United States

Other Identifiers

LYL845-101

Identifier Type: -

Identifier Source: org_study_id