Neoantigen Derived DCs as Cancer Treatment

NCT05767684 | Recruiting Phase 1 DMC

• 1 other identifier: A-BR-108-087
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

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.

Conditions

Refractory Tumor; Solid Tumor

Keywords

immunotherapy; cancer vaccine; neoantigen

Outcome Measures

Primary Outcomes (1)

• Number of subjects experienced limiting toxicities in the first 6 weeks.

  The following toxicities that happened during first 6 weeks are considered LTs. Toxicities are graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0: * \>=Grade 3 non-hematological toxicity * \>=Grade 4 hematological toxicity * Any death not clearly due to the underlying disease or extraneous causes. * Any case meeting Hy's law * Recurrent grade 2 pneumonitis

  6 weeks

Secondary Outcomes (3)

• Percentage of patients who had a clinical response

  1 year

• Number of participants who did not progressed or survived at 1 year

  1 year

• Number of subjects experienced any ≥ grade 3 toxicities.

  1 year

Other Outcomes (1)

• Number of subjects experienced immune response

  1 year

Study Arms (2)

Arm 1: DCs monotherapy

EXPERIMENTAL

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

Biological: Dendritic Cell Vaccine

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

EXPERIMENTAL

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.

Biological: Dendritic Cell Vaccine; Drug: Lenvatinib; Drug: Nivolumab

Interventions

Dendritic Cell Vaccine 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.

Also known as: DCs

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

Lenvatinib DRUG

Lenvatinib 10mg/day on day 43-77

Also known as: Lenvima

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

Nivolumab DRUG

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

Also known as: OPDIVO

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

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Health Research Institutes, Taiwan: lead
• National Cheng-Kung University Hospital: collaborator

Study Sites (3)

Kaohsiung Medical University Hospital

Kaohsiung City, Taiwan

NOT YET RECRUITING

National Cheng-Kung University Hospital

Tainan, Taiwan

RECRUITING

National Institute of Cancer Research

Tainan, Taiwan

RECRUITING

MeSH Terms

Conditions

Neoplasms

Interventions

lenvatinib; Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Li-Tzong Chen, MD, PhD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yung-Yeh Su, MD

CONTACT

+886-6-7000123; yysu@nhri.edu.tw

Kuan-Chung Hsiao, PhD

CONTACT

+886-6-7000123; randolph.hsiao@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All patient will receive DCs monotherapy initially on day 1, 8, 15 and 29 as safety run-in. Safety and efficacy (1st CT evaluation) will be conducted at day 43. On the 1st CT evaluation, patient met randomization criteria and without progression disease/safety concern will be randomized to either observation or booster of lenvatinib and nivolumab during day 43 to 77.

Study Record Dates

• First Submitted: March 2, 2023
• First Posted: March 14, 2023
• Study Start: June 1, 2023
• Primary Completion: March 30, 2025
• Study Completion: March 30, 2026
• Last Updated: August 25, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

TW (3)