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A Study to Investigate LYL845 in Adults With Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05573035
Recruitment Status : Recruiting
First Posted : October 10, 2022
Last Update Posted : May 16, 2024
Sponsor:
Information provided by (Responsible Party):
Lyell Immunopharma, Inc.

Tracking Information
First Submitted Date  ICMJE October 6, 2022
First Posted Date  ICMJE October 10, 2022
Last Update Posted Date May 16, 2024
Actual Study Start Date  ICMJE December 19, 2022
Estimated Primary Completion Date August 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 22, 2024)
  • Incidence of dose-limiting toxicities (DLTs) [ Time Frame: Up to 28 days ]
    Evaluate incidence of dose-limiting toxicities (DLTs)
  • Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 2 years ]
    Evaluate incidence of treatment-emergent adverse events (TEAEs)
  • Severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 2 years ]
    Evaluate severity of treatment-emergent adverse events (TEAEs)
  • Determine recommended Phase 2 Dose Range (RP2DR) [ Time Frame: Up to 2 years ]
    Determine the recommended Phase 2 dose range (during dose-escalation phase)
Original Primary Outcome Measures  ICMJE
 (submitted: October 6, 2022)
  • Incidence of dose-limiting toxicities (DLTs) [ Time Frame: Up to 2 years ]
    Evaluate incidence of dose-limiting toxicities (DLTs)
  • Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 2 years ]
    Evaluate incidence of treatment-emergent adverse events (TEAEs)
  • Severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 2 years ]
    Evaluate severity of treatment-emergent adverse events (TEAEs)
  • Determine recommended Phase 2 Dose Range (RP2DR) [ Time Frame: Up to 2 years ]
    Determine the recommended Phase 2 dose range (during dose-escalation phase)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2024)
  • Overall response rate (ORR) by RECIST, version 1.1 [ Time Frame: up to 2 years ]
    Evaluate anti-tumor activity of LYL845 based on overall response rate (ORR) by RECIST, version 1.1
  • Duration of response (DOR) [ Time Frame: up to 2 years ]
    Evaluate duration of response (DOR)
  • Progression-free survival (PFS) [ Time Frame: up to 2 years ]
    Evaluate progression-free survival (PFS)
  • Overall survival (OS) [ Time Frame: up to 2 years ]
    Evaluate overall survival (OS)
Original Secondary Outcome Measures  ICMJE
 (submitted: October 6, 2022)
  • Overall response rate (ORR) by RECIST, version 1.1 [ Time Frame: up to 2 years ]
    Evaluate anti-tumor activity of LYL845 based on overall response rate (ORR) by RECIST, version 1.1
  • Complete response rate (CR) by RECIST, version 1.1 [ Time Frame: up to 2 years ]
    Evaluate anti-tumor activity of LYL845 based on complete response rate (CR) by RECIST, version 1.1
  • Duration of response (DOR) [ Time Frame: up to 2 years ]
    Evaluate duration of response (DOR)
  • Progression-free survival (PFS) [ Time Frame: up to 2 years ]
    Evaluate progression-free survival (PFS)
  • Overall survival (OS) [ Time Frame: up to 2 years ]
    Evaluate overall survival (OS)
  • Expansion of LYL845 in participants [ Time Frame: up to 2 years ]
    T-cell counts by T cell, B cell, and NK cell (TBNK) flow cytometry assay
  • T-cell phenotype of LYL845 in participants [ Time Frame: up to 2 years ]
    T-cell phenotype assay of LYL845 by flow cytometry and RNA expression profiling
  • T-cell clonal diversity of LYL845 in participants [ Time Frame: up to 2 years ]
    T-cell clonal diversity assay of LYL845 product by bulk T cell receptor sequencing (TCRseq)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Investigate LYL845 in Adults With Solid Tumors
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Single-arm, open-label, dose-escalation and -expansion study
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Melanoma
  • Non-small Cell Lung Cancer
  • Colorectal Cancer
Intervention  ICMJE Biological: LYL845
LYL845 is an autologous tumor infiltrating lymphocyte (TIL) enhanced via Epi-R, a proprietary epigenetic reprogramming technology
Study Arms  ICMJE Experimental: Experimental LYL845
Epigenetically reprogrammed tumor infiltrating lymphocyte (TIL) therapy
Intervention: Biological: LYL845
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 6, 2022)		 108
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2027
Estimated Primary Completion Date August 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lauren Levine, MD 888-707-7917 clinicaltrials@lyell.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05573035
Other Study ID Numbers  ICMJE LYL845-101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Lyell Immunopharma, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Lyell Immunopharma, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Lyell Immunopharma, Inc.
Verification Date May 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP