A Study to Investigate LYL845 in Adults With Solid Tumors
Purpose
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
Eligibility
- Eligible Ages
- Between 18 Years and 75 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
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
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Single Group Assignment
- Intervention Model Description
- Single-arm, open-label, dose-escalation and -expansion study
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Experimental LYL845 |
Epigenetically reprogrammed tumor infiltrating lymphocyte (TIL) therapy |
|
More Details
- Status
- Active, not recruiting
- Sponsor
- Lyell Immunopharma, Inc.
Study Contact
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.