A Study to Investigate LYL845 in Adults With Solid Tumors

• Sponsor: Lyell Immunopharma, Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05573035
• Collaborator: (none)
• Enrollment: 108
• Locations: 4
• Arm: 1
• Anticipated Duration (Months): 57
• Patients Per Site: 27
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Melanoma; Non-small Cell Lung Cancer; Colorectal Cancer	Biological: LYL845	Phase 1

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 108 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Single-arm, open-label, dose-escalation and -expansion studySingle-arm, open-label, dose-escalation and -expansion study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Anticipated Study Start Date: Dec 1, 2022
• Anticipated Primary Completion Date: Aug 1, 2025
• Anticipated Study Completion Date: Sep 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental LYL845 Epigenetically reprogrammed tumor infiltrating lymphocyte (TIL) therapy	Biological: LYL845; LYL845 is an autologous tumor infiltrating lymphocyte (TIL) enhanced via Epi-R, a proprietary epigenetic reprogramming technology

Outcome Measures

Primary Outcome Measures

1. Incidence of dose-limiting toxicities (DLTs) [Up to 2 years]

   Evaluate incidence of dose-limiting toxicities (DLTs)

2. Incidence of treatment-emergent adverse events (TEAEs) [Up to 2 years]

   Evaluate incidence of treatment-emergent adverse events (TEAEs)

3. Severity of treatment-emergent adverse events (TEAEs) [Up to 2 years]

   Evaluate severity of treatment-emergent adverse events (TEAEs)

4. Determine recommended Phase 2 Dose Range (RP2DR) [Up to 2 years]

   Determine the recommended Phase 2 dose range (during dose-escalation phase)

Secondary Outcome Measures

1. 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

2. Complete response rate (CR) by RECIST, version 1.1 [up to 2 years]

   Evaluate anti-tumor activity of LYL845 based on complete response rate (CR) by RECIST, version 1.1

3. Duration of response (DOR) [up to 2 years]

   Evaluate duration of response (DOR)

4. Progression-free survival (PFS) [up to 2 years]

   Evaluate progression-free survival (PFS)

5. Overall survival (OS) [up to 2 years]

   Evaluate overall survival (OS)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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) and if BRAF-mutated, BRAF/MEK inhibition

• 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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ohio State University Medical Center	Columbus	Ohio	United States	43210
2	Oregon Health Sciences University	Portland	Oregon	United States	97239
3	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
4	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah	United States	84112

Sponsors and Collaborators

• Lyell Immunopharma, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Lyell Immunopharma, Inc.
• ClinicalTrials.gov Identifier: NCT05573035
• Other Study ID Numbers: LYL845-101
• First Posted: Oct 10, 2022
• Last Update Posted: Dec 21, 2022
• Last Verified: Dec 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Lyell Immunopharma, Inc.: TIL; tumor infiltrating lymphocyte; melanoma; non-small cell lung cancer; colorectal cancer; NSCLC; CRC; relapsed; refractory; locally advanced; advanced; metastatic; epigenetic
• Additional relevant MeSH terms: Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Melanoma

Study Results

No Results Posted as of Dec 21, 2022