Neoantigen Derived DCs as Cancer Treatment

NCT ID: NCT05767684

Last Updated: 2023-08-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-01
• Study Completion Date: 2026-03-30

Brief Summary

Tumor lysate or carcinoembryonic antigen (CEA) derived DCs-based therapy is safe and can elicites remarkable T-cell responses but mostly did not really transfer into significant clinical benefit. One possible reason is the lack of effective antigen and the immunosuppressive microenvironment. Now we are exploring another new strategy, prediction of neoantigen for priming DCs as cell-based therapy with or without booster of anti-VEGF/anti-PD-1.

Detailed Description

The human immune system can recognize and destroy cancer cells but cancer cells are capable of escaping from immune system by different ways, including the PD-1/PDL-1 axis and the VEGF signaling pathway. The PD-1/PD-L1 axis represents an adaptive immune resistance mechanism exerted by tumor cells. Previous study also revealed VEGF-A could induce tumor-associated macrophages, Treg cells, and myeloid-derived suppressor cells, creating an immunosuppressive microenvironment that prevent the maturation of dendritic cells (DCs) and inhibit the activation of NK cells and T cells. Our research group already completed some early phase clinical trials of DCs-based therapy, which illustrated tumor lysate or carcinoembryonic antigen (CEA) derived DCs-based therapy is feasible and safe in patients with advanced colorectal cancer and lung cancer, respectively. However, although DCs-based therapy elicited remarkable T-cell responses but mostly did not really transfer into significant clinical benefit in previous study. One possible reason is the lack of effective antigen and the immunosuppressive microenvironment. Now we are exploring another new strategy, prediction of neoantigen for priming DCs as cell-based therapy with or without booster of anti-VEGF/anti-PD-1.

Conditions

Refractory Tumor; Solid Tumor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1: DCs monotherapy

DCs injection on day 1, 8, 15, 29, 85, 141, 197, 253 and 309.

Group Type: EXPERIMENTAL

Dendritic Cell Vaccine

Intervention Type: BIOLOGICAL

Approximately 1.5 x 10\^6±20% cells will be subcutaneously injected to the patient's inguinal area (either left side or right side can be injected, only one area will be injected each time) on day 1, 8, 15, 29, 85, 141, 197, 253 and 309.

Arm 2: DCs with booster of anti-VEGF/anti-PD-1.

DCs injection on day 1, 8, 15, 29, 85, 141, 197, 253 and 309 plus lenvatinib 10mg QD on day 43-77 and nivolumab 3mg/kg on day 43, 57 and 71.

Group Type: EXPERIMENTAL

Dendritic Cell Vaccine

Intervention Type: BIOLOGICAL

Approximately 1.5 x 10\^6±20% cells will be subcutaneously injected to the patient's inguinal area (either left side or right side can be injected, only one area will be injected each time) on day 1, 8, 15, 29, 85, 141, 197, 253 and 309.

Lenvatinib

Intervention Type: DRUG

Lenvatinib 10mg/day on day 43-77

Nivolumab

Intervention Type: DRUG

Nivolumab 3mg/kg on day 43, 57 and 71.

Interventions

Dendritic Cell Vaccine

Approximately 1.5 x 10\^6±20% cells will be subcutaneously injected to the patient's inguinal area (either left side or right side can be injected, only one area will be injected each time) on day 1, 8, 15, 29, 85, 141, 197, 253 and 309.

Intervention Type: BIOLOGICAL

Lenvatinib

Lenvatinib 10mg/day on day 43-77

Intervention Type: DRUG

Nivolumab

Nivolumab 3mg/kg on day 43, 57 and 71.

Intervention Type: DRUG

Other Intervention Names

DCs; Lenvima; OPDIVO

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

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cheng-Kung University Hospital

OTHER

Sponsor Role: collaborator

National Health Research Institutes, Taiwan

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Li-Tzong Chen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Kaohsiung Medical University Hospital, and Center for Cancer Research, Kaohsiung Medical University

Locations

Kaohsiung Medical University Hospital

Kaohsiung City, , Taiwan

Site Status: NOT_YET_RECRUITING

National Cheng-Kung University Hospital

Tainan City, , Taiwan

Site Status: RECRUITING

National Institute of Cancer Research

Tainan City, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Yung-Yeh Su, MD

Role: CONTACT

yysu@nhri.edu.tw

+886-6-7000123 ext. 65181

Kuan-Chung Hsiao, PhD

Role: CONTACT

randolph.hsiao@gmail.com

+886-6-7000123 ext. 65108

Facility Contacts

Li-Tzong Chen, MD, PhD

Role: primary

leochen@nhri.edu.tw

Yung-Yeh Su, MD

Role: primary

yysu@nhri.edu.tw

+886-6-7000123 ext. 65181

Yung-Yeh Su, MD

Role: primary

yysu@nhri.edu.tw

+8867-7000123 ext. 65181

Other Identifiers

A-BR-108-087

Identifier Type: -

Identifier Source: org_study_id