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Recruiting Phase 1/2

Dual-Targeting CAR-NK Cells in Biomarker-Selected Advanced Colorectal Cancer

NCT07589517 · tracked via the Priya Life Science China tracker
Phase
Phase 1/2
Started
2026-02-02
Last updated
2026-05-15

Condition(s) studied

Colorectal CancerMetastatic Colorectal AdenocarcinomaUnresectable Colorectal Cancer

Investigational drug(s) / intervention(s)

EB-DUO-CAR-NK-CEA/GCC →Lymphodepletion

EB-DUO-CAR-NK-CEA/GCC: ogeneic dual-target CAR-NK cells manufactured from cord blood-derived NK cells, genetically engineered to express a tandem (dual-binding) CAR, an IL-15 support element (e.g., membrane-bound IL-15 or IL-15/IL-15R fusion), and an inducible suicide switch

Lymphodepletion: Lymphodepleting chemotherapy ( fludarabine and cyclophosphamide) administered pre-infusion to facilitate CAR-NK cell engraftment.

Study summary

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.

Eligibility

Sex
ALL
Min age
18 Years
Max age
75 Years
Healthy volunteers
No
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.

Primary outcome measure(s)

  • Incidence of dose-limiting toxicities (DLTs) graded by CTCAE v5.0. — 28 Days
  • Maximum tolerated dose (MTD) — 28 Days
  • Objective response rate (ORR) by RECIST v1.1 in the expansion cohort. — 12 weeks

Trial sites (1)

FacilityCityRegionStatus
Peking University Shenzhen Hospital Shenzhen Guangdong Recruiting
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07589517 on ClinicalTrials.gov ↗ ← All trials in China