Combination of CAR-DC Vaccine and Immune Checkpoint Inhibitors for Treating Malignant Tumors

A Pilot Clinical Trial of Autologous EphA-2-Targeting Chimeric Antigen Receptor Dendritic Cell Vaccine Loaded With TP53 Mutant Peptide Plus ICIs for Local Advanced/Metastatic Solid Tumors or Relapsed/Refractory Lymphomas.

This study is testing a new vaccine combined with immune treatments to see if it can help people with advanced tumors and certain types of lymphomas fight their cancer better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Chinese PLA General Hospital (Academic / other)
• Drugs / interventions: chemotherapy, prednisone, chimeric antigen receptor
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT05631886 on ClinicalTrials.gov

What this trial studies

This pilot clinical trial evaluates the safety and efficacy of an autologous EphA2-targeting CAR-DC vaccine combined with immune checkpoint inhibitors (ICIs) in patients with local advanced or metastatic solid tumors and relapsed/refractory lymphomas. The study aims to assess the immune response generated by the vaccine and its ability to enhance T cell activity against tumor cells. Participants will receive the TP53-EphA-2-CAR-DC vaccine along with standard treatments like Abraxane and anti-PD-1/CTLA4 antibodies. The trial will monitor the safety profile and antitumor effects of this innovative therapeutic approach.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18-75 with advanced solid tumors or relapsed/refractory lymphomas that express EphA2 and have specific TP53 mutations.

Not a fit: Patients with tumors that do not express EphA2 or lack the specified TP53 mutations may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new, effective option for patients with difficult-to-treat malignant tumors.

How similar studies have performed: While the approach of combining CAR-DC vaccines with ICIs is innovative, previous studies have shown varying success with similar immunotherapeutic strategies.

Eligibility criteria

Inclusion Criteria:

1. Age 18-75 (inclusive).
2. ECOG performance status ≤2 and Estimated life expectancy of more than 3 months.
3. Local advanced/metastatic solid tumors or R/R lymphomas confirmed by histopathology or cytology with documentation of tumor EphA2 positive (≥20%) and TP53 mutation (R273H or R175H or R248Q or R249S) within 6 months prior to screening. The second malignancy is allowed.
4. No clinical response to standard frontline therapy or no standard therapy exists for solid tumors. Relapse after treatment with ≥2 lines systemic therapy or refractory disease for lymphomas. Patients who have declined standard therapy or have no access to standard therapy may be enrolled and the reasons for a lack of access need to be documented. Previous treatment with anti-PD-1/PD-L1 antibodies or anti-CTLA4 antibody are allowed, regardless of the level of PD-1/PD-L1 expression, dMMR and TMB.
5. At least one measurable lesion at baseline per RECIST version 1.1 or Lugano response criteria 2014.
6. Adequate organ function as defined by the following criteria: ANC ≥1000 cells/μL; Platelet count ≥80,000/μL; Hemoglobin ≥8.0 g/dL (hemocytopenia caused by lymphoma invasion of bone marrow is not subject to conditions); Serum AST and serum ALT, ≤3.0 x ULN (≤5 x ULN for patients with liver metastases); Total serum bilirubin ≤3.0 x ULN); Serum creatinine ≤2 x ULN or creatinine clearance of ≥45 mL/min.
7. Willing to undergo either excised or large-needle lymph node or tissue biopsy, or provide formalin-fixed paraffin-embedded (FFPE) tumor tissue block or freshly cut unstained slides.
8. Willing to complete all scheduled visits and assessments at the institution administering the therapy.
9. Able to read, understand and provide written informed consent.

Exclusion Criteria:

1. Having TP53 (R273H or R175H or R248Q or R249S) germline mutation.
2. Active central nervous system disease involvement (but allow patients with prior brain metastases treated at least 4 weeks prior to enrollment that are clinically stable and do not require intervention), or prior history of NCI CTCAE Grade ≥3 drug-related CNS toxicity.
3. Prior organ allograft transplantations or allogeneic hematopoietic stem cell transplantation.
4. Evidence of active uncontrolled viral, bacterial, or systemic fungal infection.
5. Known positive test result for human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS).
6. Active infection of hepatitis B virus (HBV), or hepatitis C virus (HCV).
7. Patients with history (within the last 5 years) or risk of autoimmune disease who have immunosuppressive medications or immunosuppressive doses of systemic corticosteroids (\>10 mg/day prednisone or equivalent) within 28 days prior to enrollment. However, patients who received a short course of corticosteroids (eg, premedication prior to antibody drug) will be eligible for study entry.
8. Major trauma or major surgery within 4 weeks prior to enrollment.
9. Previous treatment involving TP53 mutant (R273H or R175H or R248Q or R249S) and EphA2.
10. Systemic chemotherapy and other intervene within 2 weeks prior to vaccination.
11. Being participating or withdrew any other trials within 4 weeks.
12. Any serious underlying medical (eg, pulmonary, renal, hepatic, gastrointestinal, or neurological) or psychiatric condition or any issue that would limit compliance with study requirements.
13. Vaccination within 30 days of study enrollment.
14. Pregnant, lactating, or breastfeeding females.
15. Researchers believe that other reasons are not suitable for clinical trials.

Where this trial is running

Beijing, Beijing Municipality

• Biotherapeutic Department of Chinsese PLA Gereral Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Weidong Han, Ph.D

Conditions Solid Tumor, Adult; Lymphoma; EphA2 Overexpression; TP53 R273H; TP53 R175H; TP53 R248Q; TP53 R249S; Local Advanced/Metastatic