Combination of CAR-DC Vaccine and ICIs in Malignant Tumors

Launched by CHINESE PLA GENERAL HOSPITAL · Nov 29, 2022

Keywords

ClinConnect Summary

This clinical trial is exploring a new treatment for adults with certain types of advanced solid tumors or specific lymphomas that have not responded to standard therapies. The study is looking at a combination of a special vaccine designed to target cancer cells (called the EphA2-targeting CAR-DC vaccine) and immune checkpoint inhibitors (ICIs), which are medications that help the body’s immune system fight cancer. The main goals are to see how safe this combination is, how well it works to reduce tumors, and how the body’s immune system responds to the treatment.

To participate in the trial, you need to be between 18 and 75 years old and have a confirmed diagnosis of an advanced solid tumor or lymphoma that has specific genetic changes. You must also have at least one measurable tumor and be willing to undergo a biopsy (a small tissue sample) for testing. If you meet these criteria, you can expect to receive the new treatment and be monitored closely for any effects. It’s important to note that this is a pilot study, which means it’s one of the first steps in testing this treatment, and researchers are eager to learn more about its potential benefits and risks.

Gender

ALL

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.