A Study of CNA3103 (LGR5-targeted, Autologous CAR-T Cells) Administered to Subjects With Metastatic Colorectal Cancer

NCT 05759728

 

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.

Intervention / Treatment 

  • BiologicalCNA3103: 5 x 10^7 cells
  • BiologicalCNA3103: 1.5 x 10^8 cells
  • BiologicalCNA3103: 4.5 x 10^8 cells
  • BiologicalCNA3103: 1.5 x 10^9 cells
  • BiologicalCNA3103: 2.5 x 10^7 cells

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.

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