Combination of CAR-DC Vaccine and ICIs in 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.
Chinese PLA General Hospital
10 participants
Jul 4, 2023
INTERVENTIONAL
Conditions
Summary
This is a pilot clinical trial for subjects with local advanced/metastatic solid tumors or relapsed/refractory (R/R) lymphomas to determine the safety, efficacy and immune response of autologous EphA2-targeting CAR-DC vaccine loaded with TP53 mutant peptide (TP53-EphA-2-CAR-DC) in combination with ICIs. It aims to: assess the safety and antitumor effects of TP53-EphA-2-CAR-DC vaccine; detect T cell response against TP53 mutant peptide and tumor neoepitopes after the treatment with TP53-EphA-2-CAR-DC vaccine and ICIs.
Eligibility
Inclusion Criteria9
- Age 18-75 (inclusive).
- ECOG performance status ≤2 and Estimated life expectancy of more than 3 months.
- 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.
- 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.
- At least one measurable lesion at baseline per RECIST version 1.1 or Lugano response criteria 2014.
- 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.
- 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.
- Willing to complete all scheduled visits and assessments at the institution administering the therapy.
- Able to read, understand and provide written informed consent.
Exclusion Criteria15
- Having TP53 (R273H or R175H or R248Q or R249S) germline mutation.
- 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.
- Prior organ allograft transplantations or allogeneic hematopoietic stem cell transplantation.
- Evidence of active uncontrolled viral, bacterial, or systemic fungal infection.
- Known positive test result for human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS).
- Active infection of hepatitis B virus (HBV), or hepatitis C virus (HCV).
- 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.
- Major trauma or major surgery within 4 weeks prior to enrollment.
- Previous treatment involving TP53 mutant (R273H or R175H or R248Q or R249S) and EphA2.
- Systemic chemotherapy and other intervene within 2 weeks prior to vaccination.
- Being participating or withdrew any other trials within 4 weeks.
- Any serious underlying medical (eg, pulmonary, renal, hepatic, gastrointestinal, or neurological) or psychiatric condition or any issue that would limit compliance with study requirements.
- Vaccination within 30 days of study enrollment.
- Pregnant, lactating, or breastfeeding females.
- Researchers believe that other reasons are not suitable for clinical trials.
Interventions
5\~10 × 10\^6 CAR DCs per dose will be administered by intravenous injection.
Intravenous abraxane 125 mg/m\^2/day on day-5.
Intravenous cyclophosphamide 300 mg/m\^2/day on day -4.
Intravenous anti-PD-1 antibody 200 mg/day.
Intravenous anti-CTLA4 antibody 1 mg/kg/day
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT05631886