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

Trial details

Who runs it

Beijing Biotech

Trial code

NCT07523529

Record updated

13 April 2026

Original description

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.Read full original descriptionShow less

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

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.

Inclusion: 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: Prior gene-modified cellular therapy directed against the same target pair within 6 months, or persistent clinically significant toxicity from prior cell / gene therapy; 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; Concurrent second malignancy requiring active systemic treatment, except certain low-risk or definitively treated cancers allowed by protocol; Active uncontrolled infection, including uncontrolled bacterial, fungal, or viral infection; active tuberculosis; uncontrolled HIV; active hepatitis B or C with detectable / unsafe viral burden; 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; Any condition that, in the investigator's judgment, would interfere with safe participation, product manufacture, infusion, or interpretation of results; No qualifying target pair after central review, or target pair considered unsafe because of unacceptable predicted ontarget / off-tumor risk; Pregnancy or breastfeeding.

ClinicalTrials.gov NCT07523529