Colorectal CancerPhase 1/2CARABiNERNCT05319314
LYL273 for Patients With Relapsed or Refractory mCRC
A Phase 1/2 study testing LYL273 in people with Colorectal Cancer, run by Lyell Immunopharma, Inc. at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- LYL273
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 155 participants
- Where
- 5 sitesUnited States
- Study dates
- 1 Aug 2022to Jun 2032
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites, 5 recruiting
- Recruiting
University of Colorado Hospital - Anschutz Cancer Pavilion
Aurora, Colorado, 80045
Meredith Waring, 303-724-9840, meredith.waring@cuanschutz.edu
Alexander Pung, 303-724-9632, alexander.pung@cuanschutz.edu
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215-5418
Jamie Dela Cruz, 857-215-2833, jamiep_delacruz@dfci.harvard.edu
- Recruiting
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Jessica Mathias, 626-218-4088, jmathias@coh.org
Kimberly Le, 626-218-2997, kimle@coh.org
- Recruiting
SCRI Oncology Partners and Tristar Centennial Hospital
Nashville, Tennessee, 37203
SCRI Oncology Partners, 629-309-1550, clemence.walker@scri.com
- Recruiting
University of California San Francisco Medical Center
San Francisco, California, 94143
UCSF Team, 415-353-2421, HDFCCC.CIP@ucsf.edu
About this study
Official title: A Phase 1/2 Multicenter Study Evaluating the Safety and Efficacy of LYL273 in Patients With Relapsed or Refractory Metastatic Colorectal Cancer
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.
Read the 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.
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.
- Conditions
- Colorectal Cancer
- Being tested
- LYL273
- 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
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LYL273Drug
Single infusion of Chimeric Antigen Receptor (CAR) transduced autologous T cells administered intravenously (i.v.)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: LYL273 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Incidence of adverse events (AEs) defined as dose-limiting toxicities (DLTs) during 3+3 dose escalation study
Measured: 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
Measured: 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
Measured: 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
Measured: Baseline to Month 18
Secondary outcomes (9)
Phase 1 and 2: Evaluate the efficacy of LYL273
ORR based on investigator assessment per RECIST Version 1.1 criteria
Measured: 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
Duration of response (DOR) based on Investigator assessment per RECIST Version 1.1 criteria.
Measured: 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
Time to response based on Investigator assessment per RECIST Version 1.1 criteria.
Measured: 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
Duration of response based on IRC assessment per RECIST Version 1.1 criteria
Measured: 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
Time to response based on IRC assessment per RECIST Version 1.1 criteria
Measured: 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
Progression free survival (PFS) based on Investigator assessment per RECIST Version 1.1 criteria
Measured: Infusion (Day 0) until the date of first documented progression/recurrence or date of death from any cause, whichever comes first
Phase 1 and 2: Overall Survival (OS)
Overall survival (OS)
Measured: Infusion (Day 0) until date of death from any cause
Phase 2: Incidence and severity of adverse events
Measured: Infusion (Day 0) to 3 months
Phase 1 and 2: Cellular Kinetics
Maximum concentration (Cmax), time to peak cell expansion (Tmax), area under the concentration curve from time 0 to Day 28 (AUC0-28), and cellular persistence (time of last measurable concentration [Tlast]) for the GCC CAR T cells
Measured: Infusion (Day 0) up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2022
- Study start1 Aug 2022
- Primary completionJun 2028 (estimated)
- Study completionJun 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 155 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lyell Immunopharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05319314
- Sponsor's protocol ID
- LYL273-101
- Acronym
- CARABiNER
- Status last verified
- Jun 2026
- First submitted
- 23 Mar 2022
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No