A Study to Investigate LYL845 in Adults With Solid Tumors

Phase 1

Active, not recruiting

• Conditions: Melanoma; Non-small Cell Lung Cancer; Colorectal Cancer
• Interventions: Biological: LYL845

• Registration Number: NCT05573035
• Lead Sponsor: Lyell Immunopharma, Inc.

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.

Study Timeline

• Study First Submitted: 2022-10-06
• Study First Submitted QC: 2022-10-06
• Study First Posted: 2022-10-10
• Study Start: 2022-12-19
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-05
• Last Update Posted: 2024-11-06
• Primary Completion: 2025-08
• Study Completion: 2027-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 108

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental LYL845	LYL845	Epigenetically reprogrammed tumor infiltrating lymphocyte (TIL) therapy

Primary Outcome Measures

Name	Time	Method
Incidence of dose-limiting toxicities (DLTs)	Up to 28 days	Evaluate incidence of dose-limiting toxicities (DLTs)
Determine recommended Phase 2 Dose Range (RP2DR)	Up to 2 years	Determine the recommended Phase 2 dose range (during dose-escalation phase)
Incidence of treatment-emergent adverse events (TEAEs)	Up to 2 years	Evaluate incidence of treatment-emergent adverse events (TEAEs)
Severity of treatment-emergent adverse events (TEAEs)	Up to 2 years	Evaluate severity of treatment-emergent adverse events (TEAEs)

Secondary Outcome Measures

Name	Time	Method
Overall response rate (ORR) by RECIST, version 1.1	up to 2 years	Evaluate anti-tumor activity of LYL845 based on overall response rate (ORR) by RECIST, version 1.1
Overall survival (OS)	up to 2 years	Evaluate overall survival (OS)
Duration of response (DOR)	up to 2 years	Evaluate duration of response (DOR)
Progression-free survival (PFS)	up to 2 years	Evaluate progression-free survival (PFS)

Trial Locations

Locations (18)

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, 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