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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05759728




Registration number
NCT05759728
Ethics application status
Date submitted
13/02/2023
Date registered
8/03/2023
Date last updated
19/03/2024

Titles & IDs
Public title
A Study of CNA3103 (LGR5-targeted, Autologous CAR-T Cells) Administered to Subjects With Metastatic Colorectal Cancer
Scientific 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
Secondary ID [1] 0 0
CNA3103-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer Metastatic 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - CNA3103: 5 x 10^7 cells
Other interventions - CNA3103: 1.5 x 10^8 cells
Other interventions - CNA3103: 4.5 x 10^8 cells
Other interventions - CNA3103: 1.5 x 10^9 cells
Other interventions - CNA3103: 2.5 x 10^7 cells

Experimental: CNA3103 Monotherapy - Single intravenous dose of CNA3103 at Day 0


Other interventions: CNA3103: 5 x 10^7 cells
CNA3103: 5 x 10^7 cells - intravenous infusion

Other interventions: CNA3103: 1.5 x 10^8 cells
CNA3103: 1.5 x 10^8 cells - intravenous infusion

Other interventions: CNA3103: 4.5 x 10^8 cells
CNA3103: 4.5 x 10^8 cells - intravenous infusion

Other interventions: CNA3103: 1.5 x 10^9 cells
CNA3103: 1.5 x 10^9 cells - intravenous infusion

Other interventions: CNA3103: 2.5 x 10^7 cells
CNA3103: 2.5 x 10^7 cells - intravenous infusion
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To determine the safety of treatment with CNA3103.
Timepoint [1] 0 0
24 Months
Primary outcome [2] 0 0
To determine the overall best response to CNA3103.
Timepoint [2] 0 0
24 Months
Secondary outcome [1] 0 0
To determine the recommended Phase 2a dose (RP2D) of CNA3103
Timepoint [1] 0 0
28 days
Secondary outcome [2] 0 0
To monitor for replication competent viral construct in blood specimens
Timepoint [2] 0 0
24 Months
Secondary outcome [3] 0 0
To determine the Pharmacokinetics of CNA3103
Timepoint [3] 0 0
24 Months
Secondary outcome [4] 0 0
To determine overall survival
Timepoint [4] 0 0
24 Months
Secondary outcome [5] 0 0
Failure to treat
Timepoint [5] 0 0
8 Weeks
Secondary outcome [6] 0 0
To determine progression-free survival
Timepoint [6] 0 0
24 months

Eligibility
Key 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 5-FU, oxaliplatin and irinotecan-based regimens for metastatic disease.

- Positive for any level of LGR5 expression in tumor biopsies.

- Measurable or evaluable disease per RECIST version 1.1 .

- 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 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 third-space fluid collections 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/10/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2027
Actual
Sample size
Target
45
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Carina Biotech Investigators - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Carina Biotech Limited
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05759728
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Lina T Jablonskis, PhD
Address 0 0
Country 0 0
Phone 0 0
+ 61 8 7110 0883
Fax 0 0
Email 0 0
lina@carinabiotech.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05759728