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

NCT05759728 | Recruiting Phase 1 FDA Drug

• 1 other identifier: CNA3103-001
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer Metastatic

Keywords

CAR-T; LGR5

Outcome Measures

Primary Outcomes (2)

• To determine the safety of treatment with CNA3103.

  Incidence of Treatment-Emergent Adverse Events

  24 Months

• To determine the overall best response to CNA3103.

  Best response per Response Evaluation Criteria in Solid Tumors (RECIST).

  24 Months

Secondary Outcomes (6)

• To determine the recommended Phase 2a dose (RP2D) of CNA3103

  28 days

• To monitor for replication competent viral construct in blood specimens

  24 Months

• To determine the Pharmacokinetics of CNA3103

  24 Months

• To determine overall survival

  24 Months

• Failure to treat

  8 Weeks

Study Arms (1)

CNA3103 Monotherapy

EXPERIMENTAL

Single intravenous dose of CNA3103 at Day 0

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; Biological: CNA3103: 6.75 × 10^8 cells

Interventions

CNA3103: 5 x 10^7 cells BIOLOGICAL

CNA3103: 5 x 10\^7 cells - intravenous infusion

CNA3103 Monotherapy

CNA3103: 1.5 x 10^9 cells BIOLOGICAL

CNA3103: 1.5 x 10\^9 cells - intravenous infusion

CNA3103 Monotherapy

CNA3103: 2.5 x 10^7 cells BIOLOGICAL

CNA3103: 2.5 x 10\^7 cells - intravenous infusion

CNA3103 Monotherapy

CNA3103: 1.5 x 10^8 cells BIOLOGICAL

CNA3103: 1.5 x 10\^8 cells - intravenous infusion

CNA3103 Monotherapy

CNA3103: 4.5 x 10^8 cells BIOLOGICAL

CNA3103: 4.5 x 10\^8 cells - intravenous infusion

CNA3103 Monotherapy

CNA3103: 6.75 × 10^8 cells BIOLOGICAL

CNA3103: 6.75 × 10\^8 cells - intravenous infusion

CNA3103 Monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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. Anti-Kirsten rat sarcoma virus (Anti-KRAS) agents are also allowable. 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. Subjects with lung metastases involving less than or equal to 20% of both lung fields and with good respiratory reserves would be deemed eligible as long as the lesions do not compromise airways, vascular, pleural, or mediastinal spaces. Both measurable and non-measurable (evaluable) lesions would count for this assessment.
• Subjects whose lung metastases involve more than 20% of both lung fields should be discussed with the Sponsor in more detail, taking into account disease tempo, clinical symptoms, respiratory function and compromise (current or impending) of airways, vascular, pleural, or mediastinal spaces. Both measurable and non-measurable (evaluable) lesions would count for this assessment.
• 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.

You may not qualify if:

• 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 (excluding bridging 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.

Sponsors & Collaborators

• Carina Biotech Limited: lead

Study Sites (1)

Carina Biotech Investigators

Adelaide, South Australia, 5000, Australia

RECRUITING

Central Study Contacts

Lina T Jablonskis, PhD

CONTACT

+ 61 439 283 445; lina@carinabiotech.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2023
• First Posted: March 8, 2023
• Study Start: October 24, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: January 13, 2026

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)