A Phase 1/2 Multicenter Study Evaluating the Safety and Efficacy of LYL273 in Patients With Relapsed or Refractory Metastatic Colorectal Cancer
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Lyell Immunopharma, Inc.
- Enrollment
- 155
- Locations
- 4
- Primary Endpoint
- Phase 1: Maximum tolerable dose (MTD) based on incidence of dose-limiting toxicities (DLTs) during 3+3 dose escalation study
Study Overview
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.
Detailed Description
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.
- 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
- 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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
LYL273
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.
Intervention: LYL273 (Drug)
Outcomes
Primary Outcomes
Phase 1: Maximum tolerable dose (MTD) based on incidence of dose-limiting toxicities (DLTs) during 3+3 dose escalation study
Time Frame: Infusion (Day 0) to Day 28
Phase 1: Incidence of adverse events (AEs) defined as dose-limiting toxicities (DLTs) during 3+3 dose escalation study
Time Frame: 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
Time Frame: Baseline to Month 18
Phase 1: Recommended Phase 2 dose (RP2D) based on incidence of dose-limiting toxicities (DLTs) during 3+3 dose escalation study
Time Frame: Infusion (Day 0) to Day 28
Secondary Outcomes
- 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(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: Overall Survival (OS)(Infusion (Day 0) until date of death from any cause)
- Phase 2: Incidence and severity of adverse events(Infusion (Day 0) to 3 months)
- Phase 1 and 2: Cellular Kinetics(Infusion (Day 0) 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 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 progression/recurrence or date of death from any cause, whichever comes first)