Clinical Trial Finder

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

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.

Arms

Experimental: Experimental LYL845

Epigenetically reprogrammed tumor infiltrating lymphocyte (TIL) therapy

Interventions

Biological: - LYL845

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