A Study to Investigate LYL845 in Adults With Solid Tumors

Colorectal Cancer Clinical Trial

Official title:

A Phase 1 Study to Assess the Safety and Efficacy of LYL845 in Adults With Relapsed and/or Refractory Metastatic or Locally Advanced Melanoma and Selected Solid Tumor Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05573035
• Other study ID #: LYL845-101
• Status: Recruiting
• Phase: Phase 1
• Start date: December 19, 2022
• Est. completion date: September 2027

Study information

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

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 108
• Est. completion date: September 2027
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Colorectal Cancer
• Colorectal Neoplasms
• Melanoma
• Non-small Cell Lung Cancer

Intervention

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

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Ohio State University Medical Center	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Hackensack Meridian Health Inc	Hackensack	New Jersey
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Yale Cancer Center, Yale University	New Haven	Connecticut
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Oregon Health Sciences University	Portland	Oregon
United States	UC Davis Coomprehensive Cancer Center	Sacramento	California
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah
United States	UCLA Medical Center	Santa Monica	California
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	Stanford University	Stanford	California
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	Incidence of dose-limiting toxicities (DLTs)	Evaluate incidence of dose-limiting toxicities (DLTs)	Up to 28 days
Primary	Incidence of treatment-emergent adverse events (TEAEs)	Evaluate incidence of treatment-emergent adverse events (TEAEs)	Up to 2 years
Primary	Severity of treatment-emergent adverse events (TEAEs)	Evaluate severity of treatment-emergent adverse events (TEAEs)	Up to 2 years
Primary	Determine recommended Phase 2 Dose Range (RP2DR)	Determine the recommended Phase 2 dose range (during dose-escalation phase)	Up to 2 years
Secondary	Overall response rate (ORR) by RECIST, version 1.1	Evaluate anti-tumor activity of LYL845 based on overall response rate (ORR) by RECIST, version 1.1	up to 2 years
Secondary	Duration of response (DOR)	Evaluate duration of response (DOR)	up to 2 years
Secondary	Progression-free survival (PFS)	Evaluate progression-free survival (PFS)	up to 2 years
Secondary	Overall survival (OS)	Evaluate overall survival (OS)	up to 2 years