CAR-DC Vaccine and ICIs in Local Advanced/Metastatic Solid Tumors

NCT05631899 | Active Not Recruiting Phase 1

• 1 other identifier: CHN-PLAGH-BT-074
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot clinical trial for subjects with local advanced/metastatic solid tumors to determine the safety, efficacy and immune response of autologous EphA2-targeting CAR-DC vaccine loaded with KRAS mutant peptide (KRAS-EphA-2-CAR-DC) in combination with ICIs. It aims to: assess the safety and antitumor effects of KRAS-EphA-2-CAR-DC vaccine; detect T cell response against KRAS mutant peptide and tumor neoepitopes after the treatment with KRAS-EphA-2-CAR-DC vaccine and ICIs.

Conditions

Solid Tumor, Adult; EphA2 Overexpression; KRAS G12V; KRAS G12C; KRAS G12D

Keywords

Local Advanced/Metastatic

Outcome Measures

Primary Outcomes (4)

• Incidence of treatment related adverse events (AEs)

  Determining the safety profile following the initiation of treatment and grading these toxicities by CTCAE v5.0. AEs such as cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria.

  2 years

• Clinical Response

  Clinical response will be determined by RECIST 1.1 and iRECIST criteria. Response rate is the proportion of patients that achieve CR and PR.

  2 years

• Disease Control

  Disease control will be determined by RECIST 1.1 and iRECIST criteria. Disease control rate is the proportion of patients that achieve CR, PR and SD.

  2 years

• Immune Response

  Immune response will be evaluated by phenotype and functional analysis of vaccine-reactive T cells and Neoantigen-reactive T cells as well as other immune cells in peripheral blood and tumor samples. Response is defined by ≥3 folds increase relative to pre-vaccination.

  Peripheral blood: baseline, weekly before Week 9, prior to each vaccination after Week 9 until last vaccination and 1 year after last vaccine. Tumor tissue: baseline, Week 3, and following timing will be performed according to subject's condition.

Secondary Outcomes (6)

• Progression Free Survival (PFS)

  2 years

• Overall Survival (OS)

  2 years

• Time to response (TTR)

  2 years

• Duration of response (DOR)

  2 years

• Number and copy number of KRAS-EphA-2-CAR-DCs

  Peripheral blood samples are collected on days 0, 3, 7, 10, 22, the day before each vaccination until last vaccination and 1 year after last vaccine. Tumor tissues are collected at baseline, the day before Week 5, and after combination.

Study Arms (3)

KRAS-EphA-2-CAR-DC

EXPERIMENTAL

In the priming phase, a conditioning chemotherapy regimen of Abraxane and cyclophosphamide is administered three days before vaccination, and KRAS-EphA-2-CAR-DC vaccine is infused on Day 0 and Day 7 in Week 1. In the boost phase, KRAS-EphA-2-CAR-DC vaccine is infused one dose every 4 weeks since Week 5 for a total of 6 to 8 doses, then maintenance vaccination is given one dose every 8 weeks, until: 1. Unacceptable toxicity occurred or disease progression; or 2. Reactive T cells are undetected repeatedly after the last vaccine dose; or 3. Vaccine exhaustion.

Biological: KRAS-EphA-2-CAR-DC; Drug: Abraxane; Drug: Cyclophosphamide

KRAS-EphA-2-CAR-DC plus anti-PD-1 antibody

EXPERIMENTAL

In the priming phase, a conditioning chemotherapy regimen of Abraxane and cyclophosphamide is administered three days before vaccination, and KRAS-EphA-2-CAR-DC vaccine is infused on Day 0 and Day 7 in Week 1. In the boost phase, KRAS-EphA-2-CAR-DC vaccine is infused one dose every 4 weeks since Week 5 for a total of 6 to 8 doses, then maintenance vaccination is given one dose every 8 weeks. Anti-PD-1 antibody is administered 2 days after the first dose of KRAS-EphA-2-CAR-DC vaccine in the boost phase (Day 3 in Week 5) and every 4 weeks afterwards, until: 1. Unacceptable toxicity occurred or disease progression; or 2. Reactive T cells are undetected repeatedly after the last vaccine dose; or 3. Vaccine exhaustion.

Biological: KRAS-EphA-2-CAR-DC; Drug: Abraxane; Drug: Cyclophosphamide; Drug: Anti-PD-1 antibody

KRAS-EphA-2-CAR-DC plus anti-PD-1 antibody and anti-CTLA4 antibody

EXPERIMENTAL

In the priming phase, a conditioning chemotherapy regimen of Abraxane and cyclophosphamide is administered three days before vaccination, and KRAS-EphA-2-CAR-DC vaccine is infused on Day 0 and Day 7 in Week 1. In the boost phase, KRAS-EphA-2-CAR-DC vaccine is infused one dose every 8 weeks since Week 5. Anti-PD-1 antibody and anti-CTLA4 antibody are administered 2 days after the first dose of KRAS-EphA-2-CAR-DC vaccine in the boost phase (Day 3 in Week 5) and every 3 weeks afterwards for four doses, followed by anti-PD-1 antibody once every 3 weeks, until: 1. Unacceptable toxicity occurred or disease progression; or 2. Reactive T cells are undetected repeatedly after the last vaccine dose; or 3. Vaccine exhaustion.

Biological: KRAS-EphA-2-CAR-DC; Drug: Abraxane; Drug: Cyclophosphamide; Drug: Anti-PD-1 antibody; Drug: Anti-CTLA4 Monoclonal Antibody

Interventions

KRAS-EphA-2-CAR-DC BIOLOGICAL

5\~10 × 10\^6 CAR-DCs per dose will be administered by intravenous injection.

KRAS-EphA-2-CAR-DC; KRAS-EphA-2-CAR-DC plus anti-PD-1 antibody; KRAS-EphA-2-CAR-DC plus anti-PD-1 antibody and anti-CTLA4 antibody

Abraxane DRUG

Intravenous abraxane 125 mg/m\^2/day on day-5.

Also known as: Abraxane Injectable Product

KRAS-EphA-2-CAR-DC; KRAS-EphA-2-CAR-DC plus anti-PD-1 antibody; KRAS-EphA-2-CAR-DC plus anti-PD-1 antibody and anti-CTLA4 antibody

Cyclophosphamide DRUG

Intravenous cyclophosphamide 300 mg/m\^2/day on day -4.

Also known as: Cyclophosphamide for Injection

KRAS-EphA-2-CAR-DC; KRAS-EphA-2-CAR-DC plus anti-PD-1 antibody; KRAS-EphA-2-CAR-DC plus anti-PD-1 antibody and anti-CTLA4 antibody

Anti-PD-1 antibody DRUG

Intravenous anti-PD-1 antibody 200 mg/day.

Also known as: PD-1 blocking antibody

KRAS-EphA-2-CAR-DC plus anti-PD-1 antibody; KRAS-EphA-2-CAR-DC plus anti-PD-1 antibody and anti-CTLA4 antibody

Anti-CTLA4 Monoclonal Antibody DRUG

Intravenous anti-CTLA4 antibody 1 mg/kg/day

Also known as: Ipilimumab

KRAS-EphA-2-CAR-DC plus anti-PD-1 antibody and anti-CTLA4 antibody

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 (inclusive).
• ECOG performance status ≤2 and Estimated life expectancy of more than 3 months.
• 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.
• 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.
• At least one measurable lesion at baseline per RECIST version 1.1.
• 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.
• 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 therapy.
• Able to read, understand and provide written informed consent.

You may not qualify if:

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

Sponsors & Collaborators

• Chinese PLA General Hospital: lead
• Zhejiang University: collaborator

Study Sites (1)

Biotherapeutic Department of Chinsese PLA Gereral Hospital

Beijing, Beijing Municipality, 100853, China

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Albumin-Bound Paclitaxel; Cyclophosphamide; Injections; spartalizumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Drug Administration Routes; Drug Therapy; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Study Officials

• Yang Xu, Ph.D

  Zhejiang University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Biotherapeutic Department

Study Record Dates

• First Submitted: November 21, 2022
• First Posted: November 30, 2022
• Study Start: April 3, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: November 24, 2025

Record last verified: 2025-11

Locations

CN (1)