A Study to Investigate LYL845 in Adults With Solid Tumors

Inclusion Criteria:

1. Age ≥ 18 years up to ≤ 75 years at the time of informed consent
2. 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
3. Participants must have received prior systemic treatment for their metastatic disease or locally advanced disease based on tumor type as follows:
4. Melanoma: participants with disease progression following an immune checkpoint inhibitor (CPI)
5. 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
6. 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.
7. Measurable disease including at least 1 lesion that is safely resectable AND a target lesion to measure response and an additional lesion for biopsy
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
9. Adequate organ and marrow function
10. Women of childbearing potential must have a negative pregnancy test at screening
11. All participants must agree to practice highly effective methods of contraception
12. Fully recovered from toxicity from prior systemic anticancer therapy

Exclusion Criteria:

1. Prior treatment with adoptive cellular therapy
2. Prior solid organ transplantation
3. Central nervous system (CNS) involvement of disease that is extensive, symptomatic or untreated, or patients with leptomeningeal disease
4. Uncontrolled or symptomatic pleural effusion or ascites
5. Untreated or active systemic infection
6. Active autoimmune disease requiring treatment or primary immunodeficiency syndrome
7. Systemic corticosteroids at a dose of >10 mg of prednisone or equivalent per day
8. Other primary malignancy within 3 years prior to enrollment
9. Impaired cardiac function or clinically significant cardiovascular disease
10. Required chronic anticoagulation, such as warfarin, low molecular weight heparin, or Factor Xa inhibitors
11. Pregnant or nursing (lactating) women