Health TrialsbyHealthPanel

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

ConditionsColorectal CancerMetastatic Colorectal AdenocarcinomaUnresectable Colorectal Cancer
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorBeijing Biotech

About this trial

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 criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • EB-DUO-CAR-NK-CEA/GCC

    Biological/Vaccine

    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

    Drug

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

Treatment groups

48 Participants
are divided into 3 treatment groups
Group A: Arm A: CEA+GUCY2C Dual CAR-NKExperimental treatment 2 interventions
Group B: CEA+HER2 Dual CAR-NKExperimental treatment 2 interventions
Group C: GUCY2C+HER2 Dual CAR-NKExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Incidence of dose-limiting toxicities (DLTs) graded by CTCAE v5.0.

Time frame
28 Days
2

Maximum tolerated dose (MTD)

Time frame
28 Days
3

Objective response rate (ORR) by RECIST v1.1 in the expansion cohort.

Time frame
12 weeks

Secondary outcomes

1

Incidence and severity of adverse events (AEs)

Time frame
24 months
2

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

Time frame
24 months
3

Progression-free survival (PFS)

Time frame
24 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Beijing Biotech

Lead sponsor

Source ClinicalTrials.gov
Apply now