Dual-target CAR-NK therapy for advanced colorectal cancer with CEA, GUCY2C, or HER2 markers
Official title: A Phase 1/2, Biomarker-Assigned, Open-Label Dose Escalation and Expansion Study of Allogeneic Dual-Target CAR-NK Cells Targeting CEA (CEACAM5) and/or GUCY2C (GCC) With an Exploratory HER2/ERBB2-Positive Cohort in Subjects With Advanced or Metastatic Colorectal Cancer
Run by Beijing Biotech · NCT07462650 · Data updated 2026-11-12
This trial tests an off-the-shelf CAR-NK cell treatment that targets two tumor markers to see if it can shrink tumors in adults with advanced or metastatic colorectal cancer whose tumors express those markers.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Enrollment | 48 (estimated) |
| Sponsor | Beijing Biotech Industry-sponsored |
| Drugs / interventions | CAR-T, chemotherapy, cyclophosphamide, fludarabine, chimeric antigen receptor |
| Locations | 1 site (Shenzhen, Guangdong) |
| Status | Recruiting |
| Started | February 1, 2026 |
| Main results expected | December 21, 2027 |
| Study ends | December 22, 2028 |
| Registry record updated | March 10, 2026 |
| Trial ID | NCT07462650 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Ideal candidates are adults with unresectable or metastatic colorectal adenocarcinoma who have progressed on or are ineligible for standard therapies, have ECOG 0–1, adequate organ function, measurable disease, and tumor co-expression of one of the required antigen pairs per central testing.
✕Probably not a fit
Patients whose tumors do not meet the required antigen co-expression thresholds, who have uncontrolled infections or active untreated central nervous system metastases, or who have poor performance status are unlikely to benefit from this study.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This Phase 1/2 open-label trial gives an allogeneic dual-target CAR-NK cell product intravenously to adults with unresectable or metastatic colorectal adenocarcinoma whose tumors meet biomarker thresholds. Participants are assigned to one of three antigen-pair arms (CEA+GUCY2C, CEA+HER2, or GUCY2C+HER2) based on central laboratory IHC and HER2 testing, and the study begins with dose escalation to define safety and a recommended dose. After dose escalation, a prespecified selection algorithm combining DLT rate, manufacturing feasibility, early response/disease control signals, CAR-NK persistence, and biomarker engagement will nominate the target pair for dose expansion. The trial focuses on safety, tolerability, feasibility of an off-the-shelf CAR-NK approach, and preliminary anti-tumor activity in a biomarker-selected CRC population.
Why it matters
Potential benefit: If successful, this approach could provide an off-the-shelf cell therapy that reduces antigen escape and shrinks tumors while causing less severe immune toxicity than some CAR-T approaches.
How similar studies have gone: Early CAR-NK trials in hematologic cancers have shown encouraging safety and some activity, but dual-target CAR-NK approaches in solid tumors such as colorectal cancer are largely novel and have limited clinical evidence to date.
Who can join: the full rules
Show full inclusion / exclusion criteria
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's running
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Peking University Shenzhen Hospital
Shenzhen, Guangdong, China Recruiting
Study contacts
- Study coordinator: Seni S Lu, Phd
- Email: Seni-Lu@beijing-biotech.com
- Phone: +86 13076790030
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.