LYL273 for Patients With Relapsed or Refractory mCRC

NCT05319314 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: LYL273-101
• Study Type: interventional
• Target: 155
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Colorectal Cancer

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Phase 1: Incidence of adverse events (AEs) defined as dose-limiting toxicities (DLTs) during 3+3 dose escalation study

  Infusion (Day 0) to Day 28

• Phase 1: Maximum tolerable dose (MTD) based on incidence of dose-limiting toxicities (DLTs) during 3+3 dose escalation study

  Infusion (Day 0) to Day 28

• Phase 1: Recommended Phase 2 dose (RP2D) based on incidence of dose-limiting toxicities (DLTs) during 3+3 dose escalation study

  Infusion (Day 0) to Day 28

• Phase 2: Estimate the efficacy of LYL273, as measured by overall response rate (ORR) based on Independent Review Committee (IRC) assessment per Response Evaluation Criteria in Solid Tumors RECIST Version 1.1 criteria

  Baseline to Month 18

Secondary Outcomes (9)

• Phase 1 and 2: Evaluate the efficacy of LYL273

  Infusion (Day 0) until the date of first documented confirmed complete or partial response per RECIST Version 1.1 criteria, assessed up to 18 months

• Phase 1 and 2: Evaluate the efficacy of LYL273

  Date of first documented confirmed complete or partial response per RECIST Version 1.1 criteria until the date of disease progression or recurrence or date of death whichever comes first

• Phase 1 and 2: Evaluate the efficacy of LYL273

  Infusion (Day 0) until the date of first documented confirmed complete or partial response per RECIST Version 1.1 criteria, assessed up to 18 months

• Phase 2: Evaluate the efficacy of LYL273

  Date of first documented confirmed complete or partial response per RECIST Version 1.1 criteria until the date of disease progression or recurrence or date of death whichever comes first

• Phase 2: Evaluate the efficacy of LYL273

  Infusion (Day 0) until the date of first documented confirmed complete or partial response per RECIST Version 1.1 criteria, assessed up to 18 months

Study Arms (1)

LYL273

EXPERIMENTAL

Single infusion of LYL273 at the dose assigned to an individual participant. All participants will receive the same investigational therapy with the dose administered dependent upon the dose level they are assigned to in a sequential manner.

Drug: LYL273

Interventions

LYL273 DRUG

Single infusion of Chimeric Antigen Receptor (CAR) transduced autologous T cells administered intravenously (i.v.)

LYL273

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 may not qualify 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

Sponsors & Collaborators

• Lyell Immunopharma, Inc.: lead

Study Sites (4)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

RECRUITING

University of California San Francisco Medical Center

San Francisco, California, 94143, United States

RECRUITING

University of Colorado Hospital - Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215-5418, United States

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2022
• First Posted: April 8, 2022
• Study Start: August 1, 2022
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2032
• Last Updated: June 9, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)