Clinical trial NCT05573035: A Study to Investigate LYL845 in Adults With Solid Tumors
Official title: A Phase 1 Study to Assess the Safety and Efficacy of LYL845 in Adults With Relapsed and/or Refractory Metastatic or Locally Advanced Melanoma and Selected Solid Tumor Malignancies
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Melanoma
Non-small Cell Lung Cancer
Colorectal Cancer
Keywords: TIL
tumor infiltrating lymphocyte
melanoma
non-small cell lung cancer
colorectal cancer
NSCLC
CRC
relapsed
refractory
locally advanced
advanced
metastatic
epigenetic
Lead sponsor: Lyell Immunopharma, Inc.
Sponsor class: INDUSTRY
First posted: 2022-10-10
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single-arm, open-label, dose-escalation and -expansion study
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence of dose-limiting toxicities (DLTs)
timeFrame: Up to 28 days
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 2 years
measure: Severity of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 2 years
measure: Determine recommended Phase 2 Dose Range (RP2DR)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Overall response rate (ORR) by RECIST, version 1.1
timeFrame: up to 2 years
measure: Duration of response (DOR)
timeFrame: up to 2 years
measure: Progression-free survival (PFS)
timeFrame: up to 2 years
measure: Overall survival (OS)
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: UC Davis Coomprehensive Cancer Center
state: California
city: Santa Monica
country: United States
facility: UCLA Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: New Haven
country: United States
facility: Yale Cancer Center, Yale University
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Comprehensive Cancer Center
state: Minnesota
city: Hackensack
country: United States
facility: Hackensack Meridian Health Inc
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute at University of Utah
state: Utah
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
Study officials:
References: