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.
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 40 days prior to CNA3103 dosing.~Participants will receive 1 or 2 Intravenous doses of CNA3103, 2 months apart.~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.