Trial Title:
A Study of CNA3103 (LGR5-targeted, Autologous CAR-T Cells) Administered to Subjects With Metastatic Colorectal Cancer
NCT ID:
NCT05759728
Condition:
Colorectal Cancer Metastatic
Conditions: Official terms:
Colorectal Neoplasms
Conditions: Keywords:
CAR-T
LGR5
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
CNA3103: 5 x 10^7 cells
Description:
CNA3103: 5 x 10^7 cells - intravenous infusion
Arm group label:
CNA3103 Monotherapy
Intervention type:
Biological
Intervention name:
CNA3103: 1.5 x 10^8 cells
Description:
CNA3103: 1.5 x 10^8 cells - intravenous infusion
Arm group label:
CNA3103 Monotherapy
Intervention type:
Biological
Intervention name:
CNA3103: 4.5 x 10^8 cells
Description:
CNA3103: 4.5 x 10^8 cells - intravenous infusion
Arm group label:
CNA3103 Monotherapy
Intervention type:
Biological
Intervention name:
CNA3103: 1.5 x 10^9 cells
Description:
CNA3103: 1.5 x 10^9 cells - intravenous infusion
Arm group label:
CNA3103 Monotherapy
Intervention type:
Biological
Intervention name:
CNA3103: 2.5 x 10^7 cells
Description:
CNA3103: 2.5 x 10^7 cells - intravenous infusion
Arm group label:
CNA3103 Monotherapy
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.
Criteria for eligibility:
Criteria:
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.
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Carina Biotech Investigators
Address:
City:
Adelaide
Zip:
5000
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Lina T Jablonskis, PhD
Phone:
+ 61 8 7110 0883
Email:
lina@carinabiotech.com
Start date:
October 24, 2023
Completion date:
December 2027
Lead sponsor:
Agency:
Carina Biotech Limited
Agency class:
Industry
Source:
Carina Biotech Limited
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05759728
