Colorectal Cancer MetastaticPhase 1/2NCT05759728
A Study of CNA3103 (LGR5-targeted, Autologous CAR-T Cells) Administered to Subjects With Metastatic Colorectal Cancer
A Phase 1/2 study testing CNA3103: 5 x 10^7 cells, CNA3103: 1.5 x 10^8 cells and CNA3103: 4.5 x 10^8 cells in people with Colorectal Cancer Metastatic, run by Carina Biotech Limited at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer Metastatic
- What is being tested?
- CNA3103: 5 x 10^7 cells, CNA3103: 1.5 x 10^8 cells and CNA3103: 4.5 x 10^8 cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteAustralia
- Study dates
- 24 Oct 2023to Dec 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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
- 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.
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- 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.
- Normal organ and marrow function.
- No clinically significant abnormalities in urinalysis results at Screening.
- No known clinically significant gastrointestinal disease within 28 days prior to enrolment.
- No ongoing requirement for anti-diarrheal therapy.
- For female subjects of childbearing potential and male subjects with partners of childbearing potential, agreement (by subject and/or partner) to use a highly effective form of contraception and to continue its use for 6 months after the last dose of IP.
- Women of childbearing potential must have a negative serum pregnancy test within 72 hours prior to CNA3103 administration.
Who cannot join
- 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.
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- 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.
- Known central nervous system (CNS) disease.
- Current use of medications that may have the potential of QTc prolongation.
- Uncontrolled bacterial, viral, or fungal infection, requiring systemic therapy.
- Has a known infection with human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C, alcoholic or other hepatitis, or cirrhosis.
- Inability to be venipunctured and/or tolerate venous access.
- Second malignancies within 5 years prior to enrollment, except for those with a negligible risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent.
- Active autoimmune disease that is not controlled by non-steroidal anti-inflammatory drugs (NSAIDs), inhaled corticosteroids, or the equivalent of ≤10 mg/day prednisone.
- History of inflammatory bowel disease (active or past) or active peptic ulcer disease.
- History of connective tissue disorders.
- History of chronic leukemias.
- History of previous, whole abdomen radiation therapy (or total pelvic radiation therapy) or more than Grade 1 residual toxicity from previous radiation therapy.
- High cardiovascular risk, including, but not limited to, recent coronary stenting or myocardial infarction in the past year
- Left ventricular ejection fraction <50%.
- Have had a venous thromboembolic event requiring anticoagulation.
- Congenital or acquired long QT syndrome.
- QTc prolongation.
- History of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.
- Patients with ascites, previous drainage of ascites, peritoneal caking, and/or significant peritoneal deposits at Baseline are excluded from participation in the study
- Patients with reduced liver reserves and/or possibility of hepatobiliary complications, including, but not limited to; portal hypertension, liver resection (segmentectomy, metastasectomy) in the previous 6 months, patients with existing biliary stents or the need to receive a biliary stent to relieve bile duct obstruction of any etiology, patients with cholelithiasis, patients who abuse alcohol or paracetamol (with or without concomitant alcohol abuse), patients who use herbal medicines, and patients with substance abuse.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Australia1 site, 1 recruiting
- Recruiting
Carina Biotech Investigators
Adelaide, South Australia, 5000
Lina T Jablonskis, PhD, + 61 439 283 445, lina@carinabiotech.com
About this study
Official title: 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
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.
Read more
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.
Read the 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.
- Conditions
- Colorectal Cancer Metastatic
- Being tested
- CNA3103: 5 x 10^7 cells, CNA3103: 1.5 x 10^8 cells, CNA3103: 4.5 x 10^8 cells, CNA3103: 1.5 x 10^9 cells, CNA3103: 2.5 x 10^7 cells
- Keywords
- CAR-T, LGR5
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CNA3103: 5 x 10^7 cellsBiological
CNA3103: 5 x 10^7 cells - intravenous infusion
CNA3103: 1.5 x 10^8 cellsBiological
CNA3103: 1.5 x 10^8 cells - intravenous infusion
CNA3103: 4.5 x 10^8 cellsBiological
CNA3103: 4.5 x 10^8 cells - intravenous infusion
CNA3103: 1.5 x 10^9 cellsBiological
CNA3103: 1.5 x 10^9 cells - intravenous infusion
CNA3103: 2.5 x 10^7 cellsBiological
CNA3103: 2.5 x 10^7 cells - intravenous infusion
CNA3103: 6.75 × 10^8 cellsBiological
CNA3103: 6.75 × 10^8 cells - intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| CNA3103 Monotherapy | Experimental | Single intravenous dose of CNA3103 at Day 0 Receives: Biological: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety of treatment with CNA3103.
Incidence of Treatment-Emergent Adverse Events
Measured: 24 Months
To determine the overall best response to CNA3103.
Best response per Response Evaluation Criteria in Solid Tumors (RECIST).
Measured: 24 Months
Secondary outcomes (6)
To determine the recommended Phase 2a dose (RP2D) of CNA3103
Determined by dose limiting toxicities (DLTs)
Measured: 28 days
To monitor for replication competent viral construct in blood specimens
Viral construct presence will be monitored
Measured: 24 Months
To determine the Pharmacokinetics of CNA3103
Levels of CNA3103 cells measured
Measured: 24 Months
To determine overall survival
Survival will be calculated from the onset of CNA3103 therapy.
Measured: 24 Months
Failure to treat
Caused by manufacturing issues or patient related issues.
Measured: 8 Weeks
To determine progression-free survival
Calculated from the onset of therapy to disease progression.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2023
- Study start24 Oct 2023
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Cancer MetastaticStudies 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
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Carina Biotech Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05759728
- Sponsor's protocol ID
- CNA3103-001
- Status last verified
- Jun 2025
- First submitted
- 13 Feb 2023
- Last updated
- 13 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05759728
- Acronym / sponsor ID
- CNA3103-001
- Conditions
- Colorectal Cancer Metastatic
- Keywords
- CAR-T, LGR5
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Carina Biotech LimitedIndustry (pharma, biotech, devices)
- Study start
- 24 Oct 2023 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 8 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CNA3103 Monotherapy | Experimental | Biological: 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 cellsSingle intravenous dose of CNA3103 at Day 0 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
Key exclusion criteria (29 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CNA3103: 5 x 10^7 cellsCNA3103: 5 x 10^7 cells - intravenous infusion | Biological | CNA3103 Monotherapy |
| CNA3103: 1.5 x 10^8 cellsCNA3103: 1.5 x 10^8 cells - intravenous infusion | Biological | CNA3103 Monotherapy |
| CNA3103: 4.5 x 10^8 cellsCNA3103: 4.5 x 10^8 cells - intravenous infusion | Biological | CNA3103 Monotherapy |
| CNA3103: 1.5 x 10^9 cellsCNA3103: 1.5 x 10^9 cells - intravenous infusion | Biological | CNA3103 Monotherapy |
| CNA3103: 2.5 x 10^7 cellsCNA3103: 2.5 x 10^7 cells - intravenous infusion | Biological | CNA3103 Monotherapy |
| CNA3103: 6.75 × 10^8 cellsCNA3103: 6.75 × 10^8 cells - intravenous infusion | Biological | CNA3103 Monotherapy |
Primary outcome
To determine the safety of treatment with CNA3103.
Time frame: 24 Months
Incidence of Treatment-Emergent Adverse Events
To determine the overall best response to CNA3103.
Time frame: 24 Months
Best response per Response Evaluation Criteria in Solid Tumors (RECIST).
6 secondary outcomes
To determine the recommended Phase 2a dose (RP2D) of CNA3103
Time frame: 28 days
To monitor for replication competent viral construct in blood specimens
Time frame: 24 Months
To determine the Pharmacokinetics of CNA3103
Time frame: 24 Months
To determine overall survival
Time frame: 24 Months
Failure to treat
Time frame: 8 Weeks
To determine progression-free survival
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CNA3103: 5 x 10^7 cells, CNA3103: 1.5 x 10^8 cells and CNA3103: 4.5 x 10^8 cells in people with Colorectal Cancer Metastatic, run by Carina Biotech Limited at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lina T Jablonskis, PhD (+ 61 439 283 445, lina@carinabiotech.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the safety of treatment with CNA3103. (time frame: 24 Months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2026.