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 Cellsthe basic structural and functional unit of all living things), for participants with Metastatic Colorectalrelating to the colon or rectum in the large bowel/intestine Cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs.
Participants may undergo a pre-screening biopsyremoval of a section of tissue to analyse for cancer cells procedure to determine expression of LGR5.
Participants will undergo screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening procedures, including leukapheresisa procedure used to quickly reduce dangerously high levels of white blood cells to a safer level (collection of T cells) and lymphodepletion (chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells), up to 47 days prior to CNA3103 dosing.
Participants will receive a single Intravenousinto or within a vein dosethe amount of medication taken 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.
Intervention / Treatment
- 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
Inclusion Criteria:
- Signed written Informed Consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment..
- Male and female subjects aged greater than or equal to18 years.
- Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer 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 recurrenceto occur or happen again/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 Gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells ≤ 1, with the exception of neuropathy and alopeciathe partial or complete absence of hair from areas of the body where it normally grows; baldness.
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.