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A Study of CNA3103 (LGR5-targeted, Autologous CAR-T Cells) Administered to Subjects With Metastatic Colorectal Cancer | Clinical Trials | Clareo Health

RECRUITINGPHASE1/PHASE2

A Study of CNA3103 (LGR5-targeted, Autologous CAR-T Cells) Administered to Subjects With Metastatic Colorectal Cancer

A Phase 1/2a, Multicenter, Open-Label, Dose Escalation and Expansion Study of CNA3103 (LGR5-targeted, Autologous CAR-T Cells) Administered to Adult Subjects With Metastatic Colorectal Cancer

NCT05759728•Carina Biotech Limited

View on ClinicalTrials.gov

Summary

This study aims to determine the safety and best response of treatment with CNA3103 (Leucine-rich repeat-containing G protein-coupled receptor 5 \[LGR5\]-targeted, Autologous Chimeric Antigen Receptor (CAR) -T Cells), for participants with Metastatic Colorectal Cancer. Participants may undergo a pre-screening biopsy procedure to determine expression of LGR5. Participants will undergo screening procedures, including leukapheresis (collection of T cells) and lymphodepletion (chemotherapy), up to 47 days prior to CNA3103 dosing. Participants will receive a single Intravenous dose of CNA3103. Expansion cohorts will open after determination of the maximum tolerated dose and recommended phase 2 dose in the dose escalation stage. Participants will be followed up, monitored and will attend study visits for safety and research related tests and procedures for 2 years until disease progression, unacceptable toxicity or intolerable adverse event/s, death or withdrawal of consent.

Detailed Description

This is a Phase 1/2a, multicenter, open-label study in adult subjects with metastatic colorectal cancer. (CRC). The study will consist of 2 segments: Phase 1 Segment (Dose Escalation): a Bayesian Optimal Interval (BOIN) study design will be used to minimize any risks of exposure to the novel CNA3103 CAR-T cells during dose escalation while determining the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D). A minimum of 3 subjects per cohort will be enrolled at each dose level, with appropriate staggering of subjects within and between dose levels. Phase 2a Segment (Dose Expansion): After determination of the MTD/RP2D, additional subjects will be enrolled and treated with CNA3103 at that dose to further assess the safety, PK, pharmacodynamic, and anti-tumor properties of CNA3103. Based upon safety data of these additional subjects, the Sponsor, in consult with the Investigators, may choose to enroll additional subjects at the same or a different dose.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Signed written Informed Consent.
•Male and female subjects aged greater than or equal to18 years.
•Eastern Cooperative Oncology Group (ECOG) Performance Score 0 to 1.
•Histologically or cytologically confirmed metastatic colorectal cancer previously treated with no more than 2 prior fluoropyrimidine, oxaliplatin, and/or irinotecan-based regimens for metastatic disease. Antibody-drug conjugates (ADCs) administered in the metastatic setting are also considered cytotoxic treatment and would count as a prior regimen. Neoadjuvant/adjuvant treatment of resectable oligometastatic disease, does not count as a prior line of therapy in the palliative setting unless there is development of an unresectable local or distant recurrence within 6 months of its last dose.
•Subjects who discontinue their prior regimen due to toxicity (in the absence of disease recurrence/progression) will also have their prior therapy count as one prior regimen. Anti-Kirsten rat sarcoma virus (Anti-KRAS) agents are also allowable. The planned lymphodepletion start date must be at least 4 weeks from last chemotherapy, biologic, radiotherapy, or investigational therapy (excluding bridging therapy), with resolution of all lingering toxicities to Grade ≤ 1, with the exception of neuropathy and alopecia.
•Subjects previously treated in the adjuvant/neoadjuvant setting with an oxaliplatin/irinotecan regimen, who develop an unresectable local recurrence and/or metastatic disease within 6 months of the date of last oxaliplatin/irinotecan chemotherapy will have their adjuvant/ neoadjuvant therapy count as one prior regimen.
•Positive for any level of LGR5 expression in tumor biopsies.
•Measurable or evaluable disease per RECIST version 1.1. Subjects with lung metastases involving less than or equal to 20% of both lung fields and with good respiratory reserves would be deemed eligible as long as the lesions do not compromise airways, vascular, pleural, or mediastinal spaces. Both measurable and non-measurable (evaluable) lesions would count for this assessment.
•Subjects whose lung metastases involve more than 20% of both lung fields should be discussed with the Sponsor in more detail, taking into account disease tempo, clinical symptoms, respiratory function and compromise (current or impending) of airways, vascular, pleural, or mediastinal spaces. Both measurable and non-measurable (evaluable) lesions would count for this assessment.
•Life expectancy of at least \>12 weeks.
+6 more criteria

Exclusion Criteria

•Inability to comply with study and follow-up procedures.
•Women who are pregnant or lactating.
•Has BRAF-mutated colorectal cancer.
•Has received trifluridine/tipiracil (TAS-102) or regorafenib for metastatic disease.
•Treatment with chemotherapy, hormonal therapy, immunotherapy, biologic therapy, or radiation therapy as cancer therapy (excluding bridging therapy) within 4 weeks prior to the lymphodepletion start date.
•Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent in the previous 28 days prior to enrolment.
•Have received antibody-based therapies within the previous 28 days or 5 half-lives of the agent, whichever is shorter.
•Major surgery, in the previous 4 weeks prior to enrolment.
•Clinically detectable pleural effusion requiring drainage in the 4 weeks prior to enrolment.
•Any uncontrolled medical or psychiatric risk factors which would contraindicate the use or impair the ability of the subject to provide informed consent, receive protocol therapy or may impose excessive risk to the subject.
+19 more criteria

Locations (1)

Carina Biotech Investigators

Adelaide, South Australia, Australia

Key Dates

Start Date

October 24, 2023

Primary Completion Date

December 1, 2027

Completion Date

December 1, 2027

Last Updated

January 13, 2026

Enrollment

ESTIMATED participants

Conditions

Colorectal Cancer Metastatic

Interventions

CNA3103: 5 x 10^7 cells

BIOLOGICAL

CNA3103: 1.5 x 10^8 cells

BIOLOGICAL

CNA3103: 4.5 x 10^8 cells

BIOLOGICAL

CNA3103: 1.5 x 10^9 cells

BIOLOGICAL

CNA3103: 2.5 x 10^7 cells

BIOLOGICAL

CNA3103: 6.75 × 10^8 cells

BIOLOGICAL

Contacts

Lina T Jablonskis, PhD

CONTACT

+ 61 439 283 445 lina@carinabiotech.com

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: January 13, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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A Study of CNA3103 (LGR5-targeted, Autologous CAR-T Cells) Administered to Subjects With Metastatic Colorectal Cancer

Inclusion Criteria

Exclusion Criteria

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