Colorectal Cancer, Melanoma, Non-small Cell Lung Cancer
Conditions
Keywords
TIL, tumor infiltrating lymphocyte, melanoma, non-small cell lung cancer, colorectal cancer, NSCLC, CRC, relapsed, refractory, locally advanced, advanced, metastatic, epigenetic
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.
Interventions
BIOLOGICALLYL845
LYL845 is an autologous tumor infiltrating lymphocyte (TIL) enhanced via Epi-R, a proprietary epigenetic reprogramming technology
Sponsors
Lyell Immunopharma, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single-arm, open-label, dose-escalation and -expansion study
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine recommended Phase 2 Dose Range (RP2DR) | Up to 2 years | Determine the recommended Phase 2 dose range (during dose-escalation phase) |
| Incidence of dose-limiting toxicities (DLTs) | Up to 28 days | Evaluate incidence of dose-limiting toxicities (DLTs) |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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) |
| Overall survival (OS) | up to 2 years | Evaluate overall survival (OS) |
Countries
United States
Outcome results
None listed