A Study to Investigate LYL845 in Adults With Solid Tumors

NCT05573035 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: LYL845-101
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 18

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).

Conditions

Melanoma; Non-small Cell Lung Cancer; Colorectal Cancer

Keywords

TIL; tumor infiltrating lymphocyte; melanoma; non-small cell lung cancer; colorectal cancer; NSCLC; CRC; relapsed; refractory; locally advanced; advanced; metastatic; epigenetic

Outcome Measures

Primary Outcomes (4)

• Incidence of dose-limiting toxicities (DLTs)

  Evaluate incidence of dose-limiting toxicities (DLTs)

  Up to 28 days

• Incidence of treatment-emergent adverse events (TEAEs)

  Evaluate incidence of treatment-emergent adverse events (TEAEs)

  Up to 2 years

• Severity of treatment-emergent adverse events (TEAEs)

  Evaluate severity of treatment-emergent adverse events (TEAEs)

  Up to 2 years

• Determine recommended Phase 2 Dose Range (RP2DR)

  Determine the recommended Phase 2 dose range (during dose-escalation phase)

  Up to 2 years

Secondary Outcomes (4)

• Overall response rate (ORR) by RECIST, version 1.1

  up to 2 years

• Duration of response (DOR)

  up to 2 years

• Progression-free survival (PFS)

  up to 2 years

• Overall survival (OS)

  up to 2 years

Study Arms (1)

Experimental LYL845

EXPERIMENTAL

Epigenetically reprogrammed tumor infiltrating lymphocyte (TIL) therapy

Biological: LYL845

Interventions

LYL845 BIOLOGICAL

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

Experimental LYL845

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Lyell Immunopharma, Inc.: lead

Study Sites (18)

UC Davis Coomprehensive Cancer Center

Sacramento, California, 95817, United States

Location

UCLA Medical Center

Santa Monica, California, 90404, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Yale Cancer Center, Yale University

New Haven, Connecticut, 06511, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic Comprehensive Cancer Center

Rochester, Minnesota, 55905, United States

Location

Hackensack Meridian Health Inc

Hackensack, New Jersey, 07601, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, 84112, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Melanoma; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Recurrence; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single-arm, open-label, dose-escalation and -expansion study

Study Record Dates

• First Submitted: October 6, 2022
• First Posted: October 10, 2022
• Study Start: December 19, 2022
• Primary Completion: January 9, 2025
• Study Completion: January 9, 2025
• Last Updated: July 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (18)