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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT05759728
Ethics application status
Date submitted
13/02/2023
Date registered
8/03/2023
Date last updated
19/09/2024

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Step 2 (Medium Dose) - A total of 12 participants will receive three injections, spaced by two weeks, of Glycovax-002 Medium Dose or placebo (ratio 3:1).
Comparator / control treatment
Control group

Outcomes

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 no more than 2 prior fluoropyrimidine, oxaliplatin, and/or irinotecan-based regimens for metastatic disease. 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.

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.
* 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 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
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)

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/study/NCT05759728
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

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
[email protected]
Contact person for scientific queries



Summary Results

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