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

NCT07589517 | Recruiting Phase 1 DMC

• 1 other identifier: EB-CARNK-CRC-111
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Colorectal Cancer; Unresectable Colorectal Cancer; Metastatic Colorectal Adenocarcinoma

Keywords

CAR-NK; Dual-target CAR; CEACAM5; CEA; GUCY2C; GCC; HER2; ERBB2; Solid tumor immunotherapy; Allogeneic NK cells; Adoptive cell therapy

Outcome Measures

Primary Outcomes (3)

• 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

Secondary Outcomes (3)

• Incidence and severity of adverse events (AEs)

  24 months

• Disease control rate (DCR) and duration of response (DoR) by RECIST v1.1.

  24 months

• Progression-free survival (PFS)

  24 months

Study Arms (3)

Arm A: CEA+GUCY2C Dual CAR-NK

EXPERIMENTAL

CRC with tumor co-expression of CEA (CEACAM5) and GUCY2C (GCC) above prespecified thresholds

Biological: EB-DUO-CAR-NK-CEA/GCC; Drug: Lymphodepletion

CEA+HER2 Dual CAR-NK

EXPERIMENTAL

CRC with CEA expression and HER2/ERBB2 positivity

Biological: EB-DUO-CAR-NK-CEA/GCC; Drug: Lymphodepletion

GUCY2C+HER2 Dual CAR-NK

EXPERIMENTAL

CRC with GUCY2C expression and HER2/ERBB2 positivity

Biological: EB-DUO-CAR-NK-CEA/GCC; Drug: Lymphodepletion

Interventions

EB-DUO-CAR-NK-CEA/GCC BIOLOGICAL

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

Arm A: CEA+GUCY2C Dual CAR-NK; CEA+HER2 Dual CAR-NK; GUCY2C+HER2 Dual CAR-NK

Lymphodepletion DRUG

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

Arm A: CEA+GUCY2C Dual CAR-NK; CEA+HER2 Dual CAR-NK; GUCY2C+HER2 Dual CAR-NK

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Biotech: lead

Study Sites (1)

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Seni S Lu, Phd

CONTACT

+86 13076790030; Seni-Lu@beijing-biotech.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: pen-label administration; endpoint assessment follows RECIST v1.1 by investigator and/or independent review
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A: 3+3 dose-escalation in each biomarker-defined target-pair arm. Part B: expansion cohort in the selected target pair at RP2D (one or more expansions may be opened based on Part A results).

Study Record Dates

• First Submitted: May 10, 2026
• First Posted: May 15, 2026
• Study Start: February 2, 2026
• Primary Completion (Estimated): March 14, 2027
• Study Completion (Estimated): March 17, 2028
• Last Updated: May 15, 2026

Record last verified: 2026-05

Locations

CN (1)