Using neoantigen-derived dendritic cells to treat cancer

Personalized Neoantigen Derived Dendritic Cell-Based Immunotherapy as Cancer Treatment

This study is testing a new cancer treatment using specially prepared immune cells to see if it can help people with hard-to-treat solid tumors feel better and live longer.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 20 Years and up
• Sex: All
• Sponsor: National Health Research Institutes, Taiwan (other)
• Drugs / interventions: prednisone
• Locations: 3 sites (Kaohsiung and 2 other locations)
• Trial ID: NCT05767684 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates a novel immunotherapy approach using dendritic cells (DCs) primed with neoantigens to treat patients with refractory solid tumors, including advanced pancreatic, liver, biliary tract, and colorectal cancers. The study aims to enhance the immune response against cancer cells by overcoming the immunosuppressive microenvironment that typically hinders effective treatment. Participants will receive a DC vaccine, potentially combined with anti-VEGF and anti-PD-1 therapies, to improve clinical outcomes. The trial will assess the safety and efficacy of this innovative treatment strategy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 20 and older with stage IV solid tumors that are refractory or intolerant to standard therapies.

Not a fit: Patients with sarcoma or neuroendocrine tumors, as well as those without adequate organ function or immune system status, may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to improved immune responses and better clinical outcomes for patients with difficult-to-treat cancers.

How similar studies have performed: While previous studies have shown promise with dendritic cell-based therapies, this specific approach using neoantigens is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* ≥20 years of age
* Provide written informed consent
* Histologically confirmed stage IV pancreatic cancer, liver cancer, biliary tract cancer and colorectal cancer (excluding sarcoma and neuroendocrine tumor) that refractory or intolerance to standard therapies for their condition (there is no effective treatment by investigator judgement)
* Completed tumor and germline DNA and RNA sequencing and the neoantigen prediction
* Patients with chronic hepatitis B is eligible if receiving anti-hepatitis B agents and the HBV DNA level \< 2000 IU/ml prior to the preparation phase. Patients with chronic hepatitis C are eligible if HCV RNA is undetectable (\<15 IU/ml) prior to the preparation phase
* Adequate organ function

  * Absolute neutrophil count \>1000/mcL
  * Hemoglobin \> 8.0 g/dl
  * Platelet \> 50000/mcL
  * PT/aPTT \< 1.5 x upper limit of normal (ULN)
  * AST/ALT \< 3 x ULN
  * Bil(T) \< 1.5 x ULN
  * BUN/Cr \< 1.5 x ULN
* Adequate immune system as defined by

  * IgG \> 614 mg/dl
  * IgM \> 53mg/dl
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
* Life expectancy at least\>12weeks
* At least one measurable target lesion as defined by RECIST 1.1

Exclusion Criteria:

* Sarcoma、neuroendocrine tumor
* Last anticancer therapy administered within 2 weeks and any AEs should be ≤ grade 2 prior to leukapheresis
* Patients who cannot tolerate leukapheresis and follow-up blood sampling of 50ml at day 43, day 85 and end-of- treatment.
* Any known active infection as judged by the investigator
* Any known chronic active infection of HIV, HTLV-1 or HTLV-2
* Requirement of systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to the screen phase. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
* Other immunocompromising condition that in the opinion of the treating physician renders the patient a poor candidate for this trial
* Pregnant women, nursing women, men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device (IUD), abstinence, etc.)
* Patients with history of penicillin allergy
* Other medical problems or conditions that, in the opinion of the investigator, would make participation in the study hazardous for the patient

Where this trial is running

Kaohsiung and 2 other locations

• Kaohsiung Medical University Hospital — Kaohsiung, Taiwan (NOT_YET_RECRUITING)
• National Cheng-Kung University Hospital — Tainan, Taiwan (RECRUITING)
• National Institute of Cancer Research — Tainan, Taiwan (RECRUITING)

Study contacts

• Principal investigator: Li-Tzong Chen, MD, PhD — Kaohsiung Medical University Hospital, and Center for Cancer Research, Kaohsiung Medical University
• Study coordinator: Yung-Yeh Su, MD

Conditions: Refractory Tumor, Solid Tumor, immunotherapy, cancer vaccine, neoantigen