Sequential Infusion of CD146-Targeted and HER2-Targeted CAR T Cells in Patients With Advanced Sarcomas

NCT07066982 | Recruiting Phase 1 DMC

• 1 other identifier: ESBI202571-103
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, non-randomized, multicenter Phase 1/2 trial evaluating a dual CAR-T cell therapy targeting CD146 and HER2 in patients with advanced sarcoma. Participants will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by sequential infusion of autologous CD146-specific and HER2-specific CAR-T cells. The Phase 1 portion will employ a dose-escalation design to assess safety and determine the recommended Phase 2 dose, while the Phase 2 expansion will evaluate preliminary efficacy (tumor response and survival outcomes). Approximately 40 patients (children and adults) with relapsed or refractory sarcomas will be enrolled across multiple centers. All participants will be followed for up to 36 months to monitor dose-limiting toxicities, objective response rates, progression-free survival, overall survival, and long-term safety.

Conditions

Sarcoma; Sarcoma, Kaposi; Sarcoma, Ewing; Sarcoma,Soft Tissue; Sarcoma of Bone and Connective Tissue; Sarcoma, Synovial; Sarcoma Metastatic; Sarcomas, Germinoblastic; Sarcoma of Bone

Keywords

Sarcoma; CD146; HER2; CAR-T; Sarcoma of Bone

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of dose-limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD19/BCMA chimeric antigen receptor (CAR) T cells

  Will be recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 at three dose levels until the maximum tolerated dose (MTD) is determined.

  28 days

Secondary Outcomes (1)

• Rate of successful manufacture and expansion of the CD146/HER-2 chimeric antigen receptor (CAR) T cells

  60 days

Study Arms (1)

CD146/HER2 CAR T cells, chemotherapy

EXPERIMENTAL

Patients will be administered fludarabine phosphate intravenously (IV) over a 30-minute period on days -4 to -2. Additionally, cyclophosphamide will be administered intravenously (IV) over 60 minutes on day -2. Subsequently, patients will receive CD146 HER-2 CAR T cells intravenously (IV) over a duration of 10-20 minutes on day 0. Patients who exhibit positive responses to the initial dose of CD146/HER2 CAR T cells, do not experience unacceptable side effects, and have a sufficient quantity of cells available may be eligible to receive 2 or 3 additional doses of CD146/HER2 CAR T cells.

Biological: CD146/HER2 CAR-T cells

Interventions

CD146/HER2 CAR-T cells BIOLOGICAL

The intervention in this clinical trial involves a novel approach using CD146/HER2 Chimeric Antigen Receptor T (CAR T) cells combined with chemotherapy. The goal is to assess safety and efficacy in patients with specific hematologic malignancies. Treatment Regimen: Patients in the trial will undergo the following regimen: Fludarabine Phosphate (Days -4 to -2): IV administration of fludarabine phosphate over 30 minutes on days -4 to -2. It's part of the preparatory regimen to enhance the body's response to CAR T-cell therapy. Cyclophosphamide (Day -2): IV cyclophosphamide over 60 minutes on day -2. BCMA/GPRC5D Chimeric Antigen Receptor T Cells (Day 0): IV administration of investigational therapy, CD146/HER-2 CAR T cells, over 10-20 minutes on day 0. Additional Doses: Eligible patients responding well to the initial CD146/HER-2 CAR-T cell infusion without unacceptable side effects and sufficient CAR-T cell availability may receive 2 or 3 additional doses.

CD146/HER2 CAR T cells, chemotherapy

Eligibility Criteria

• Age: 21 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Expected survival time ≥3 months;
• Diagnosis: Histologically or cytologically confirmed sarcoma (soft tissue or bone sarcoma), that is metastatic, locally advanced, or refractory to standard therapy. This may include osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, leiomyosarcoma, or other high-grade sarcomas. Patients must have evidence of measurable disease as per RECIST or applicable criteria.
• Prior Treatment: Patients should have received and progressed on or not be candidates for standard first-line treatments. There is no limit on number of prior lines of therapy, but at least one prior systemic therapy for sarcoma is typically required (unless no standard therapy exists for the subtype). A minimum wash-out period (e.g. 2 weeks) from previous treatments (chemotherapy, radiation, or other immunotherapy) is required before lymphodepletion.
• Age and Performance Status: Participants age 12 years and older (both adolescent and adult patients are eligible; for minors, legal guardian consent is required). Upper age limit of \~75 years, or as determined by medical fitness. ECOG performance status 0-1 (or Karnofsky ≥70% for pediatric patients), indicating subjects are ambulatory and able to perform light work.
• Organ Function: Adequate organ function to undergo cytotoxic chemotherapy and cell transfer therapy, including: cardiac ejection fraction ≥50%; baseline oxygen saturation \>92% on room air; adequate bone marrow reserves (absolute neutrophil count ≥1.0×10\^9/L, platelets ≥75×10\^9/L, hemoglobin ≥8 g/dL), hepatic function (e.g. bilirubin ≤1.5× ULN, AST/ALT ≤2.5× ULN), and renal function (e.g. creatinine clearance ≥50 mL/min or age-appropriate normal).
• Tumor Antigen Expression: Expression of CD146 and/or HER2 in the tumor is recommended (as assessed by immunohistochemistry or flow cytometry on a tumor sample). Note: At least one of the target antigens (CD146 or HER2) should be present on the tumor; if feasible, patients should have tumor tissue tested for these markers. (In cases where testing is unavailable, enrollment may proceed based on histology known to often express these targets, per investigator judgment.)
• Consent: Ability to understand and provide written informed consent (or assent for minors with consent of legal guardian). Patients (or guardians) must be willing to comply with trial procedures and follow-up.

You may not qualify if:

• Recent Therapies: Prior treatment with any CAR-T cell therapy or other gene-modified T-cell therapy is excluded. Also exclude patients who received any investigational drug, immunotherapy (e.g. checkpoint inhibitor), or major surgery within a certain interval (e.g. 4 weeks) prior to enrollment. Concurrent enrollment in another interventional clinical trial is not allowed.
• Recent Therapies: Prior treatment with any CAR-T cell therapy or other gene-modified T-cell Infections: Active uncontrolled infection, including active hepatitis B or C infection, or HIV infection with uncontrolled viral load. Patients must not have evidence of active tuberculosis or other severe infections. All patients will be screened for HBV, HCV, and HIV at baseline.
• Immunosuppression: Use of systemic immunosuppressive medications (such as chronic corticosteroids at \>10 mg prednisone daily or equivalent) within 7 days prior to leukapheresis. (Physiologic replacement doses of steroids are permitted.) Patients with a history of allogeneic stem cell transplant or solid organ transplant are excluded (due to the need for immunosuppression and risk of graft-versus-host or graft rejection).
• Medical Comorbidities: Any significant uncontrolled medical condition that would, in the investigator's judgment, make the patient an unsuitable candidate for CAR-T therapy. For example: active autoimmune diseases requiring immunosuppression, clinically significant heart failure (NYHA class III-IV), unstable angina or myocardial infarction within 6 months, severe chronic respiratory disease requiring supplemental oxygen, or psychiatric conditions that would interfere with study participation and follow-up.
• Pregnancy/Breastfeeding: Women who are pregnant or breastfeeding are excluded due to unknown risks of the treatment to a fetus or infant. Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use effective contraception during the study and for a suitable period after CAR-T infusion (e.g. 1 year), given the potential for sustained CAR T-cell activity. A negative serum pregnancy test is required for females of childbearing potential before starting lymphodepletion.

Sponsors & Collaborators

• Essen Biotech: lead

Study Sites (1)

District One Hospital

Beijing, Beijing Municipality, 086-373, China

RECRUITING

MeSH Terms

Conditions

Sarcoma; Sarcoma, Kaposi; Sarcoma, Ewing; Osteosarcoma; Sarcoma, Synovial; Lymphoma

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Neoplasms, Vascular Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Rhoda M Smith, Phd

CONTACT

+12077706670; clinical-trials@essen-biotech.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open-label clinical trials are a category of clinical research where the masking is minimal or nonexistent. In such trials, both the participants and the researchers are fully aware of the treatment assignments, which means participants know the treatment they are receiving, and researchers are aware of each participant's treatment group.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients enrolled in this clinical trial will receive a carefully designed treatment regimen. Before the infusion of HER2 and CD146 CAR-T cells, participants will undergo preconditioning chemotherapy. This chemotherapy serves to create an optimal environment for CAR-T cell therapy to effectively target and eliminate Cancer cells. Following chemotherapy, participants will receive the infusion of CD146 and HER-2 CAR-T cells.

Study Record Dates

• First Submitted: July 4, 2025
• First Posted: July 15, 2025
• Study Start: May 29, 2025
• Primary Completion (Estimated): December 10, 2027
• Study Completion (Estimated): December 28, 2028
• Last Updated: July 15, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)