NCT07523529

Brief 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
72

participants targeted

Target at P75+ for phase_1

Timeline
23mo left

Started Mar 2026

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress9%
Mar 2026Mar 2028

Study Start

First participant enrolled

March 2, 2026

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

April 5, 2026

Completed
8 days until next milestone

First Posted

Study publicly available on registry

April 13, 2026

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 14, 2027

Expected
11 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 17, 2028

Last Updated

April 13, 2026

Status Verified

April 1, 2026

Enrollment Period

1.1 years

First QC Date

April 5, 2026

Last Update Submit

April 5, 2026

Conditions

Keywords

antigen co-expressionB7-H3bi-specific CAR-TbiomarkerguidedCD133CD44CD56CD70CLDN18.2dual-target CAR-TEGFREGFRvIIIGD2gastric cancerglioblastomaGPC3HER2hepatocellular carcinomaIL13Ralpha2MesothelinMUC1NKG2DNSCLCovarian cancerpancreatic cancerPD-L1prostate cancerPSMAsolid tumorstandem CAR-TTRAIL-R2triple-negative breast cancerVEGFR1

Outcome Measures

Primary Outcomes (2)

  • Dose-limiting toxicities (DLTs)

    28 Days

  • Incidence and severity of treatment-emergent adverse events

    12 Months

Secondary Outcomes (3)

  • Objective response rate (ORR) by RECIST 1.1 or RANO

    24 Months

  • Disease control rate (DCR)

    24 Months

  • Duration of response (DoR)

    24 Months

Study Arms (1)

Biomarker-guided dual-target CAR-T therapy

EXPERIMENTAL

Participants undergo central antigen-pair screening and receive the bestmatched autologous dual-target CAR-T construct from the predefined library after lymphodepletion with fludarabine / cyclophosphamide. A second infusion may be permitted in selected participants if product is available, the assigned dose level remains safe, and retreatment criteria are met.

Biological: Autologous dual-target CAR-T cells selected from the predefined target library.Drug: FludarabineDrug: Cyclophosphamide

Interventions

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.

Biomarker-guided dual-target CAR-T therapy

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.

Also known as: lymphodepletion
Biomarker-guided dual-target CAR-T therapy

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.

Also known as: lymphodepletion
Biomarker-guided dual-target CAR-T therapy

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

RECRUITING

MeSH Terms

Conditions

Neoplasm MetastasisStomach NeoplasmsGlioblastomaCarcinoma, HepatocellularOvarian NeoplasmsPancreatic NeoplasmsProstatic NeoplasmsTriple Negative Breast Neoplasms

Interventions

fludarabineCyclophosphamide

Condition Hierarchy (Ancestors)

Neoplastic ProcessesNeoplasmsPathologic ProcessesPathological Conditions, Signs and SymptomsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesGastrointestinal DiseasesStomach DiseasesAstrocytomaGliomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueAdenocarcinomaCarcinomaLiver NeoplasmsLiver DiseasesEndocrine Gland NeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal DisordersPancreatic DiseasesGenital Neoplasms, MaleGenital Diseases, MaleProstatic DiseasesMale Urogenital DiseasesBreast NeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Masking Details
Not masked because construct selection, manufacturing release, doseescalation decisions, and acute cell-therapy toxicity monitoring require investigator awareness.
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: Single-group biomarker-guided master protocol. Every participant follows the same treatment strategy: screen for target-pair eligibility, assign the highest-ranked dual-target construct from the predefined library, administer standard lymphodepletion, then infuse the selected CAR-T product. Pair-specific dose escalation and expansion occur as subcohorts within the master protocol, but the overall study remains one non-randomized treatment strategy.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 5, 2026

First Posted

April 13, 2026

Study Start

March 2, 2026

Primary Completion (Estimated)

April 14, 2027

Study Completion (Estimated)

March 17, 2028

Last Updated

April 13, 2026

Record last verified: 2026-04

Locations