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.
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. Antibody-drug conjugates (ADCs) administered in the metastatic setting are also considered cytotoxic treatment and would count as a prior regimen. Neoadjuvant/adjuvant treatment of resectable oligometastatic disease, does not count as a prior line of therapy in the palliative setting unless there is development of an unresectable local or distant recurrence within 6 months of its last dose.
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.
Sequential
CNA3103: 5 x 10^7 cells
Biological/VaccineCNA3103: 5 x 10\^7 cells - intravenous infusion
CNA3103: 1.5 x 10^8 cells
Biological/VaccineCNA3103: 1.5 x 10\^8 cells - intravenous infusion
CNA3103: 4.5 x 10^8 cells
Biological/VaccineCNA3103: 4.5 x 10\^8 cells - intravenous infusion
CNA3103: 1.5 x 10^9 cells
Biological/VaccineCNA3103: 1.5 x 10\^9 cells - intravenous infusion
CNA3103: 2.5 x 10^7 cells
Biological/VaccineCNA3103: 2.5 x 10\^7 cells - intravenous infusion
CNA3103: 6.75 × 10^8 cells
Biological/VaccineCNA3103: 6.75 × 10\^8 cells - intravenous infusion
To determine the safety of treatment with CNA3103.
Incidence of Treatment-Emergent Adverse Events
To determine the overall best response to CNA3103.
Best response per Response Evaluation Criteria in Solid Tumors (RECIST).
To determine the recommended Phase 2a dose (RP2D) of CNA3103
Determined by dose limiting toxicities (DLTs)
To monitor for replication competent viral construct in blood specimens
Viral construct presence will be monitored
To determine the Pharmacokinetics of CNA3103
Levels of CNA3103 cells measured
To determine overall survival
Survival will be calculated from the onset of CNA3103 therapy.
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