Actively Recruiting
Dose Escalation and Expansion Study of Allogeneic Dual-Target CAR-NK Cells Targeting CEA and/or GUCY2C With HER2-Positive Cohort in Advanced or Metastatic Colorectal Cancer
Led by Beijing Biotech · Updated on 2026-05-15
48
Participants Needed
1
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the safety, tolerability, and early anti-tumor activity of a new dual-target chimeric antigen receptor natural killer (CAR-NK) cell therapy in adults with advanced or metastatic colorectal cancer. This Phase 1/2 study focuses on patients whose tumors express specific antigen pairs, aiming to improve tumor targeting and reduce escape by using combinations of CEA, GUCY2C, and HER2 markers. The study explores this innovative approach as a potentially safer, off-the-shelf cellular therapy with less risk of severe immune reactions than similar treatments. Participants are assigned to one of three groups based on tumor antigen co-expression: CEA+GUCY2C, CEA+HER2, or GUCY2C+HER2. They receive lymphodepleting chemotherapy consisting of fludarabine and cyclophosphamide before infusion with the assigned dual-target CAR-NK cells. Some participants may receive a second infusion in the same treatment cycle if safety allows. After an initial dose escalation phase, the safest and most effective target pair will be chosen for further study expansion. Throughout the study, participants will be closely monitored in the hospital during the early post-infusion period. Researchers will assess dose-limiting toxicities, maximum tolerated dose, and tumor response over 12 weeks, along with longer-term safety and disease control for up to 24 months. Tumor tissue will undergo biomarker testing to confirm eligibility and monitor treatment effects. Participation includes regular clinical evaluations, laboratory tests, and imaging to track treatment impact and safety over time.
CONDITIONS
Brief Title
Dual-Targeting CAR-NK Cells in Biomarker-Selected Advanced Colorectal Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Adults aged 18 to 75 years
- Histologically confirmed colorectal adenocarcinoma that is unresectable or metastatic
- Disease progressed after, intolerant to, or ineligible for standard therapies
- Measurable disease by RECIST v1.1 (except in planned minimal residual disease or post-resection cohorts)
- Tumor co-expression of one antigen pair: CEA+GUCY2C, CEA+HER2, or GUCY2C+HER2 per central lab thresholds
- ECOG performance status of 0 or 1
- Adequate hematologic, renal, hepatic, and cardiac function
- Recovery to Grade 61 from prior therapy toxicities (except stable Grade 2 neuropathy or alopecia)
- Life expectancy of at least 12 weeks
- Willingness to use effective contraception during and after study treatment
You will not qualify if you...
- Active, uncontrolled infections including HBV, HCV, or HIV
- Active symptomatic CNS metastases or requiring increasing steroids (stable treated CNS disease may be allowed)
- Prior gene-modified cellular therapy within 6 months or therapies increasing severe toxicity risk
- Significant autoimmune disease needing systemic immunosuppression within past 6 months
- Concurrent anti-cancer therapy during dose-limiting toxicity window (except permitted bridging)
- Pregnant or breastfeeding
- Significant cardiovascular or uncontrolled pulmonary disease
- Known allergy to study chemotherapy agents or supportive medications
- Any condition interfering with study participation, safety monitoring, or result interpretation
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - A few days before CAR-NK infusion
Participants receive lymphodepleting chemotherapy to prepare the body for CAR-NK cell infusion.
1 to 2 visits (in-person) prior to infusion
Duration - Up to 28 days per treatment cycle
Participants receive infusion(s) of dual-target CAR-NK cells targeting colorectal cancer antigens with hospitalization and close monitoring during the early post-infusion period.
1 to 2 infusions during each treatment cycle with hospitalization and close monitoring
Duration - Up to 24 months after treatment
Participants are monitored for safety, treatment response, and disease progression after treatment ends, including assessment of adverse events and disease control.
Regular visits over 24 months for safety and disease assessments
Trial Site Locations
Total: 1 location
1
Peking University Shenzhen Hospital
Shenzhen, Guangdong, China, 518036
Actively Recruiting
Research Team
S
Seni S Lu, Phd
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
3
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