a study to investigate lyl845 in adults with solid tumors

Conditions: Melanoma; Non-small Cell Lung Cancer; Colorectal Cancer

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).

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.

Eligibility criteria:
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

Keywords: til tumor infiltrating lymphocyte melanoma non-small cell lung cancer colorectal cancer nsclc crc relapsed refractory locally advanced advanced metastatic epigenetic