LYL273 for Patients With Relapsed or Refractory mCRC

a study on Colorectal Cancer Colorectal Tumor

Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCSF
Dates
study started
study ends around
Principal Investigator
by Bridget Keenan (ucsf)
Headshot of Bridget Keenan
Bridget Keenan

Description

Summary

This is a Phase 1/2 open-label, multicenter study evaluating the safety and efficacy of LYL273 in participants with relapsed or refractory metastatic colorectal cancer.

Official Title

A Phase 1/2 Multicenter Study Evaluating the Safety and Efficacy of LYL273 in Patients With Relapsed or Refractory Metastatic Colorectal Cancer

Details

LYL273-101 (CARABiNER) is a Phase 1/2 open label, multicenter study evaluating the safety, tolerability, clinical activity, pharmacokinetics and pharmacodynamics of LYL273, a GCC-targeted CAR T-cell product candidate enhanced with CD19 CAR expression and controlled cytokine release, in participants with relapsed or refractory metastatic colorectal cancer (mCRC).

The study may enroll multiple dose expansion cohorts at the Sponsor's discretion to further characterize the safety, feasibility, and preliminary antitumor activity of LYL273 under defined treatment conditions including those defined below.

  1. Cohorts to explore alternative mCRC patient populations

    Expansion cohorts may enroll a broader array of the mCRC population as listed below:

    • Earlier mCRC: Patients who have had a maximum of 1 prior line of systemic therapy
  2. Cohorts to explore LYL273 in combination with other anti-cancer therapies Expansion cohorts may explore LYL273 in combination with consolidative radiotherapy.

Up to 18 participants will be enrolled into each expansion cohort with up to approximately 95 patients enrolled in the Phase 1 portion of the study.

The Phase 2 portion of the study will expand enrollment at the recommended Phase 2 dose of approximately 60 additional patients.

LYL273 treatment consists of a single infusion of CAR-transduced autologous T cells administered intravenously after a conditioning chemotherapy regimen consisting of fludarabine and cyclophosphamide, administered once, 3 days before LYL273 infusion.

Individual participants will remain in the active post-treatment follow-up (PTFU) period for up to 5 years. Participants will continue in long-term follow-up (LTFU) for 15 years from LYL273 treatment in a separate protocol.

Keywords

Colorectal Cancer, relapsed metastatic colorectal cancer, refractory metastatic colorectal cancer, chimeric antigen receptors (CAR), metastatic colorectal cancer, mCRC, CAR T-cell, guanylyl cyclase C, GCC, colorectal neoplasms, autologous T cells, LYL273

Eligibility

You can join if…

Open to people ages 18 years and up

  • Adults > 18 years old
  • Clinical and histopathological diagnosis of relapsed or refractory metastatic colorectal cancer
  • Eastern Cooperative Oncology Group performance status of 0 or 1
  • Limited liver disease (less than 7 lesions with largest lesion less than 3 cm)
  • No surgical options with curative intent
  • Received prior therapy with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy in the advanced or metastatic setting, an anti-vascular endothelial growth factor (anti-VEGF) biological therapy if not contraindicated, and if RAS wild-type an anti-epidermal growth factor receptor (anti-EGFR) therapy in a manner consistent with National Comprehensive Cancer Network (NCCN) guidelines. Treatment must have been discontinued for disease progression or intolerance to therapy
  • Have at least one extracranial measurable target lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 standard

You CAN'T join if...

  • Participants with tumor lesion(s) in a location that may cause perforation of an organ or structure (such as the digestive tract, urinary bladder, or blood vessel) with LYL273 therapy
  • Active central nervous system (CNS) involvement by malignancy on magnetic resonance imaging (MRI) or contrast-enhanced computed tomography (CT)
  • History of or active viral infection including human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV)
  • History or presence of CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with CNS involvement in the 2-year period leading up to the study enrollment
  • No active infectious diseases or comorbid conditions that would interfere with safety or data quality
  • Pregnant or breast-feeding women

Other protocol defined Inclusion/Exclusion criteria may apply

Locations

  • University of California San Francisco Medical Center accepting new patients
    San Francisco California 94143 United States
  • City of Hope Comprehensive Cancer Center accepting new patients
    Duarte California 91010 United States
  • University of Colorado Hospital - Anschutz Cancer Pavilion accepting new patients
    Aurora Colorado 80045 United States
  • Dana-Farber Cancer Institute accepting new patients
    Boston Massachusetts 02215-5418 United States

Lead Scientist at University of California Health

  • Bridget Keenan (ucsf)
    Dr. Keenan completed her MD and PhD at the Johns Hopkins University School of Medicine, where she focused on using cancer vaccines to overcome immune suppression in the tumor microenvironment in mouse models of pancreatic cancer. She completed her Internal Medicine residency and Hematology/Oncology fellowship at UCSF.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Lyell Immunopharma, Inc.
ID
NCT05319314
Phase
Phase 1/2 research study
Study Type
Interventional
Participants
Expecting 155 study participants
Last Updated
Contact us about this trial