EphA2-targeting CAR-DC vaccine combined with immune checkpoint inhibitors for advanced solid tumors

A Pilot Clinical Trial of Autologous EphA-2-Targeting Chimeric Antigen Receptor Dendritic Cell Vaccine Loaded With KRAS Mutant Peptide in Combination With Anti-PD-1 Antibody/Anti-CTLA4 Antibody for Local Advanced/Metastatic Solid Tumors.

This study is testing a new vaccine combined with immune treatments to see if it can help people with advanced solid tumors that have specific KRAS mutations.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Chinese PLA General Hospital (other)
• Drugs / interventions: chemotherapy, prednisone, chimeric antigen receptor
• Locations: 1 site (Beijing, Beijing)
• Trial ID: NCT05631899 on ClinicalTrials.gov

What this trial studies

This pilot clinical trial evaluates the safety and efficacy of an autologous CAR-DC vaccine targeting EphA2 in patients with local advanced or metastatic solid tumors that exhibit specific KRAS mutations. The study aims to assess the immune response generated by the vaccine in combination with immune checkpoint inhibitors (ICIs) such as anti-PD-1 and anti-CTLA4 antibodies. Participants will receive the KRAS-EphA-2-CAR-DC vaccine along with standard chemotherapy agents like Abraxane and Cyclophosphamide. The trial will measure T cell responses against KRAS mutant peptides and tumor neoepitopes post-treatment.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18-75 with local advanced or metastatic solid tumors that are EphA2 positive and harbor specific KRAS mutations.

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

Why it matters

Potential benefit: If successful, this approach could enhance the immune response against solid tumors and improve treatment outcomes for patients with specific KRAS mutations.

How similar studies have performed: While therapeutic cancer vaccines have shown limited success historically, the novel approach of using CAR-DCs in combination with ICIs represents an innovative strategy that has not been extensively tested.

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 confirmed by histopathology or cytology with documentation of tumor EphA2 positive (≥20%) and KRAS mutation (G12V or G12D or G12C) within 6 months prior to screening. The second malignancy is allowed.
4. No clinical response to standard frontline therapy, or no standard therapy exists. Patients who have declined standard therapy or have no access to standard therapy may be enrolled and the reasons for 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.
6. Adequate organ function as defined by the following criteria: ANC ≥1000 cells/μL; Platelet count ≥80,000/μL; Hemoglobin ≥8.0 g/dL; 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 therapy.
9. Able to read, understand and provide written informed consent.

Exclusion Criteria:

1. Having KRAS (G12V or G12D or G12C) 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 KRAS mutant (G12V or G12D or G12C) 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

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

Study contacts

• Study coordinator: Weidong Han, Ph.D

Conditions: Solid Tumor, Adult, EphA2 Overexpression, KRAS G12V, KRAS G12C, KRAS G12D, Local Advanced/Metastatic