Personalized dual-target CAR-T therapy 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
This trial will test personalized dual-target CAR-T cells, matched to tumor biomarker patterns, in adults with advanced unresectable or metastatic solid cancers to see if dual targeting improves tumor control and safety.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 72 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Beijing Biotech Industry-sponsored |
| Drugs / interventions | CAR-T, prednisone, cyclophosphamide, fludarabine |
| Locations | 1 site (Shenzhen, Guangdong) |
| Trial ID | NCT07523529 on ClinicalTrials.gov |
What this trial studies
Participants undergo central pathology review and antigen profiling on fresh or archived tumor tissue, and a target-selection committee ranks qualifying dual-antigen pairs from a predefined library. Each participant receives lymphodepletion with fludarabine and cyclophosphamide followed by one infusion of an autologous dual-target CAR-T product chosen to match their tumor; optional repeat infusion is allowed for selected participants. New target-pair cohorts begin with a modified 3+3 dose-escalation lead-in and, if acceptable, proceed to dose expansion at the recommended Phase 2 dose/schedule with response assessed by RECIST 1.1 or RANO as appropriate. Participants are followed for disease outcomes for 24 months and monitored for long-term gene-modified cell safety for up to 15 years.
Who should consider this trial
Good fit: Adults aged 18–75 with advanced unresectable, metastatic, or recurrent solid malignancies who have failed or are not candidates for standard curative therapy and whose tumors meet the predefined dual-antigen biomarker thresholds are eligible.
Not a fit: Patients whose tumors do not express a qualifying pair of target antigens, who have inadequate organ function, or who cannot access the study site are unlikely to receive benefit from this protocol.
Why it matters
Potential benefit: If successful, this approach could improve tumor control and reduce the risk of antigen-escape by targeting two tumor antigens selected to match each patient's tumor.
How similar studies have performed: Dual-target CAR-T designs and biomarker-guided selection have shown limited promising signals in early-phase work but remain largely unproven for solid tumors.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 Criteria: * 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.
Where this trial is running
Shenzhen, Guangdong
- Peking University Shenzhen Hospital — Shenzhen, Guangdong, China (Recruiting)
Study contacts
- Study coordinator: shan S Lu, Phd
- Email: Seni-Lu@beijing-biotech.com
- Phone: +86 13076790030
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.