Dual-Targeting CAR-NK Cells in Biomarker-Selected Advanced Colorectal Cancer
Recruiting · NCT07589517 · Interventional (participants receive a specific treatment) · Lead sponsor: Beijing Biotech
View the official record on ClinicalTrials.gov →Interventions studied
EB-DUO-CAR-NK-CEA/GCCLymphodepletion
What this trial is about
This Phase 1/2 study evaluates the safety, tolerability, and preliminary anti-tumor activity of an allogeneic dual-target chimeric antigen receptor natural killer (CAR-NK) cell product in adults with advanced or metastatic colorectal cancer (CRC). Participants are assigned to one of three dual-target arms based on tumor antigen co-expression: (1) CEA+GUCY2C, (2) CEA+HER2, or (3) GUCY2C+HER2. Following dose escalation, the most suitable target pair (based on safety, feasibility, and early efficacy/biomarker signals) will be selected for dose expansion.
Who can take part
Age range
18 Years to 75 Years
Sex
All (male and female)
Healthy volunteers
No - a diagnosis or condition is required
Phase
Phase 1, Phase 2
Study type
Interventional (participants receive a specific treatment)
Inclusion criteria
- Histologically confirmed colorectal adenocarcinoma that is unresectable or metastatic and has progressed after, is intolerant to, or is ineligible for standard therapies.
- Measurable disease per RECIST v1.1 (unless in minimal residual disease (MRD) or post-resection cohorts if a future amendment is planned).
- Tumor antigen co-expression meeting central lab thresholds for one of the following pairs: CEA+GUCY2C, CEA+HER2, or GUCY2C+HER2.
- ECOG performance status 0-1.
- Adequate organ function (hematologic, renal, hepatic, and cardiac) as defined in protocol.
- Recovered to Grade ≤1 from prior therapy-related toxicities (except stable Grade 2 neuropathy or alopecia).
- Life expectancy ≥ 12 weeks.
- Willingness to use effective contraception during study and for a protocol-defined period after cell infusion.
Exclusion criteria
- Active, uncontrolled infection (including uncontrolled HBV/HCV) or known uncontrolled HIV infection.
- Active CNS metastases that are symptomatic or require escalating steroids. (Stable treated CNS disease may be allowed per protocol.)
- Prior gene-modified cellular therapy (CAR-T/CAR-NK/TCR-T) within 6 months, or any prior therapy that in the investigator's judgment increases risk of severe toxicity.
- Clinically significant autoimmune disease requiring systemic immunosuppression within the past 6 months.
- Concurrent anti-cancer therapy (other than protocol-permitted bridging) during the DLT window.
- Pregnant or breastfeeding.
- Significant cardiovascular disease (e.g., recent MI, uncontrolled arrhythmia), uncontrolled pulmonary disease, or other severe comorbidity that would increase risk.
- Known hypersensitivity to study chemotherapy components (fludarabine/cyclophosphamide) or required supportive medications.
- Any condition that, in the investigator's opinion, would interfere with study participation, safety monitoring, or interpretation of results.
Where it is running
1 location listed.
- Peking University Shenzhen Hospital - Shenzhen, Guangdong, China