RecruitingPhase 1Phase 2NCT07523529

Biomarker-Guided Dual-Target CAR-T Cells for Advanced Solid Tumors

A Phase 1/2, Open-Label, Biomarker-Guided Master Protocol Evaluating Autologous Dual-Target CAR-T Cells Selected From a Predefined Target Library in Adults With Advanced Solid Tumors

Sponsor

Beijing Biotech

Enrollment

72 participants

Start Date

Mar 2, 2026

Study Type

INTERVENTIONAL

Conditions

Metastatic Advanced Unresectable

Summary

This is a multicenter, open-label, Phase 1/2 master protocol evaluating autologous dual-target CAR-T cell therapy in adults with advanced solid cancers. After central biomarker screening, each participant is assigned the best-matched dual-target construct from a predefined target-pair library. The trial is designed to test whether biomarkerguided dual targeting can improve tumor control, reduce antigenescape risk, and preserve safety in solid tumors.

Eligibility

Min Age: 18 YearsMax Age: 75 Years

Inclusion Criteria11

Age 18-75 years at consent
Histologically or cytologically confirmed advanced unresectable, metastatic, or recurrent solid malignancy (including recurrent high-grade glioma for CNSspecific pairs) for which standard curative therapy does not exist, is not tolerated, or has failed.
At least one predefined dual-target pair qualifies on central biomarker review. Recommended working thresholds: primary antigen >= 2+ intensity in >= 50% of viable tumor cells (or pair-specific equivalent) AND secondary antigen detectable in >= 25% of viable tumor cells, with acceptable normal-tissue risk after pathology review
At least 1 measurable lesion by RECIST 1.1, or measurable / evaluable disease by RANO for CNS cohorts.
ECOG performance status 0-1 (CNS cohort may allow Karnofsky >= 70 or ECOG 0-2 if justified).
Adequate organ function: ANC >= 1.0 x 10\^9/L, platelets >= 75 x 10\^9/L, hemoglobin >= 8 g/dL, creatinine clearance >= 50 mL/min, AST / ALT <= 3 x ULN (<= 5 x ULN if liver involvement), total bilirubin <= 1.5 x ULN unless Gilbert syndrome, LVEF >= 45%, oxygen saturation >= 92% on room air.
Recovered to Grade <= 1 from acute toxicities of prior anticancer therapy (except alopecia, stable endocrinopathies, or other protocol-allowed residual toxicities).
Adequate venous access and ability to undergo leukapheresis; successful manufacture of a release-qualified autologous dual-target CAR-T product.
Life expectancy >= 12 weeks.
Negative pregnancy test for persons of childbearing potential and agreement to use highly effective contraception per protocol.
Ability to understand and sign informed consent and comply with study follow-up, including long-term gene-modified cell monitoring.

Exclusion Criteria10

No qualifying target pair after central review, or target pair considered unsafe because of unacceptable predicted ontarget / off-tumor risk.
Prior gene-modified cellular therapy directed against the same target pair within 6 months, or persistent clinically significant toxicity from prior cell / gene therapy.
Active uncontrolled infection, including uncontrolled bacterial, fungal, or viral infection; active tuberculosis; uncontrolled HIV; active hepatitis B or C with detectable / unsafe viral burden.
Need for systemic corticosteroids > 10 mg prednisone equivalent daily or other systemic immunosuppressive therapy within 7 days before lymphodepletion, unless specifically allowed for physiologic replacement or CNS edema management per cohort rules.
Active autoimmune disease requiring systemic immunosuppression within the past 2 years, except protocol-allowed stable conditions.
Clinically significant cardiovascular disease (for example uncontrolled arrhythmia, recent myocardial infarction, unstable angina, decompensated heart failure), severe pulmonary compromise, or other major comorbidity making cell therapy unsafe.
Active symptomatic CNS hemorrhage, uncontrolled seizures, or uncontrolled intracranial hypertension; leptomeningeal disease requiring urgent intervention unless explicitly allowed in a CNS-specific cohort.
Pregnancy or breastfeeding.
Concurrent second malignancy requiring active systemic treatment, except certain low-risk or definitively treated cancers allowed by protocol.
Any condition that, in the investigator's judgment, would interfere with safe participation, product manufacture, infusion, or interpretation of results.

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Interventions

BIOLOGICALAutologous dual-target CAR-T cells selected from the predefined target library.

Autologous dual-target CAR-T cells are patient-derived T cells engineered to recognize two tumor-associated antigens selected from a predefined target library. In clinical trials, they are administered to enhance tumor targeting and reduce antigen escape, with evaluation of safety, tolerability, and preliminary anti-tumor activity.

DRUGFludarabine

chemotherapy preconditioning regimen used before cell therapy to reduce the patient's existing lymphocytes and create space for infused cells. In clinical trials, it is given prior to CAR-T infusion to enhance cell expansion, persistence, and overall treatment efficacy.

DRUGCyclophosphamide

Cyclophosphamide lymphodepletion is a chemotherapy preconditioning regimen administered prior to cell therapy to suppress existing immune cells and improve the environment for infused cells. In clinical trials, it is given before CAR-T infusion to support cell expansion, persistence, and enhance therapeutic effectiveness.