Neoantigen-expanded Autologous Immune Cell Therapy

NCT05020119 | Unknown Phase 1 DMC

• 1 other identifier: DC-CIK_TRIAL_PROPOSAL
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators aim to investigate the patient's tumor neoantigen to generate "personalized cancer vaccine" and then to expand autologous dendritic cells-cytokine-induced killer cells (DC-CIK). The autologous DC-CIK will be cultured in vitro and re-infused into patients.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (3)

• Acute, subacute toxicities and AEs of neoantigen-expanded autologous immune cell therapy.

  Number of participants with ≥ grade 3 immune related Adverse Events (irAEs) as assessed by CTCAE v6.0.

  Baseline to 20 weeks after cell infusion

• Dose-limiting toxicity (DLT)

  Determination of DLT to be made after receiving the second dose of cell product of each cohort.

  Day 28

• Maximum tolerated dose (MTD)

  The dose where no DLT is observed among 3 consecutive participants, or no more than one DLT among 6 participants.

  until Day 28

Secondary Outcomes (1)

• The antitumor activity of neoantigen-expanded autologous immune cell therapy

  every 6 weeks up to 24 weeks after cell infusion.

Study Arms (3)

Low dose of neoantigen-based cell therapy (N=3+3)

EXPERIMENTAL

(1±20%) × 109cells/200 mL every 14 days for 10 doses

Drug: Neoantigen-expanded cell therapy.

Medium dose of neoantigen-based cell therapy (N=3+3)

EXPERIMENTAL

(3±20%) × 109cells/200 mL every 14 days for 10 doses

Drug: Neoantigen-expanded cell therapy.

High dose of neoantigen-based cell therapy (N=3+3)

EXPERIMENTAL

(9±20%) ×109cells/400 mL every 14 days for 10 doses

Drug: Neoantigen-expanded cell therapy.

Interventions

Neoantigen-expanded cell therapy. DRUG

Infusion of personalized neoantigen-expanded T (CIK) cells

Also known as: Neoantigen-expanded autologous DC-CIK cells.

High dose of neoantigen-based cell therapy (N=3+3); Low dose of neoantigen-based cell therapy (N=3+3); Medium dose of neoantigen-based cell therapy (N=3+3)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient has one of the following solid tumors, including colorectal cancer, gastric cancer, pancreatic cancer, esophageal cancer, liver cancer, gastrointestinal stromal tumor, biliary tract cancer, kidney cancer, bladder cancer, prostate cancer, Head and neck cancer, nasopharyngeal cancer, skin cancer, melanoma, malignant sarcoma, breast cancer, ovarian cancer, cervical cancer, endometrial cancer, lung cancer, and brain cancer.
• The patient has at least one lesion that can be obtained by sectioning or cutting to identify somatic mutations from the tumor.
• The patient diagnosed as advanced solid tumor is refractory to standard treatment; or intolerable to or unsuitable for standard treatment.When evaluating to participate in the trial, the patient must still have solid tumor.
• All patients are refractory to approved standard treatment.The definition of standard treatment for different cancers is listed below.
• Patient with colorectal cancer must have received surgery or at least two prior chemotherapies, including oxaliplatin and irinotecan; or at least one of the target therapies for colorectal cancer, including Cetuximab, Bevacizumab, Panitumumab, etc.
• Patient with gastric cancer and pancreatic cancer must have received radiotherapy, surgery, or received chemotherapies.
• Patient with esophageal cancer must have receivedthesecond-line systemic drug therapy (eg. chemotherapies or immunotherapies)
• Patient with liver cancer must havereceivedsurgery; radio-frequency ablation, or transcatheterial chemoembolization.
• Patient with biliary tract cancer must have refractory to the first-line treatment containing gemcitabine.
• Patient with gastrointestinal stromal tumors must have received the first-line target treatments.
• Patient with renal cancer must have received 2nd-line treatments (including chemotherapies or target therapies or combination with immunotherapies.
• Patient with bladder cancer must have received platinum-based chemotherapy or unable to receive chemotherapies and received immunotherapy.
• Patient with prostate cancer must have continued to disease progression or recur after receiving chemotherapies or the second-line hormone therapies.
• Patient with head and neck cancer and nasopharyngeal carcinoma must have received chemotherapies, including cetuximab or platinum.
• Patient with skin cancer and melanoma must have received at least one systemic treatment.

You may not qualify if:

• Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
• A systemic infections (e.g.: requiring anti-infective treatment), coagulation disorders, cardiovascular disease, respiratory disease, immune system disease, myocardial infarction, cardiac arrhythmia, obstructive or restrictive pulmonary disease.
• Active tuberculosis (a history of tuberculosis exposure or a positive test for tuberculosis, including clinical, physical or imaging evidence).
• Acute or chronic infectious diseases (including: syphilis or human T lymphoblast infection) (In this trial, patients with HIV, HTLV, or syphilis infection are also excluded. HIV-positive patients may have lower immunity, resulting in lower response to treatment or the toxicity after treatment is more sensitive)
• Biliary or intestinal occlusion, cholangitis or severe gastrointestinal bleeding
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease \[SCID\] and acquired immune deficiency syndrome \[AIDS\]).
• ≥ grade 4 major organ immune-related Adverse Events (irAEs) following treatment with immune checkpoint inhibitors.
• History of coronary revascularization or ischemic symptoms
• Documented left ventricular ejection fraction (LVEF) of less than or equal to 45% tested in patients with:
• Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block
• Age ≥ 60 years old
• A rapidly deteriorating disease that the trial investigators believe not be able to tolerate treatment or testing procedures

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead

Study Sites (1)

Chang Gung Memorial Hospital, Linkou

Taoyuan District, 333, Taiwan

RECRUITING

Related Publications (2)

• Zacharakis N, Chinnasamy H, Black M, Xu H, Lu YC, Zheng Z, Pasetto A, Langhan M, Shelton T, Prickett T, Gartner J, Jia L, Trebska-McGowan K, Somerville RP, Robbins PF, Rosenberg SA, Goff SL, Feldman SA. Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer. Nat Med. 2018 Jun;24(6):724-730. doi: 10.1038/s41591-018-0040-8. Epub 2018 Jun 4.

  PMID: 29867227 BACKGROUND

• Chen F, Zou Z, Du J, Su S, Shao J, Meng F, Yang J, Xu Q, Ding N, Yang Y, Liu Q, Wang Q, Sun Z, Zhou S, Du S, Wei J, Liu B. Neoantigen identification strategies enable personalized immunotherapy in refractory solid tumors. J Clin Invest. 2019 Mar 5;129(5):2056-2070. doi: 10.1172/JCI99538. Print 2019 May 1.

  PMID: 30835255 BACKGROUND

Related Links

• The protocol of this study is referenced by Zacharakis N et al. study.
• The protocol of this study is referenced by Chen F et al. study.

Study Officials

• Ming-Mo Hou, MD

  Chang Gung Memorial Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chuang-Wei Wang, PhD

CONTACT

+88633281200; kiruamairo@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending physician

Model Details: This study aims to investigate the safety profile and therapeutic potential of neoantigen-expanded autologous immune cell for treating solid tumors. The safety evaluation will be performed by a traditional 3+3 dose escalation scheme. The three cohorts will be established in the trial, and the dose level of each cohort will be enrolling 3\~6 subjects.

Study Record Dates

• First Submitted: July 30, 2021
• First Posted: August 25, 2021
• Study Start: April 9, 2021
• Primary Completion: June 30, 2022
• Study Completion: June 30, 2023
• Last Updated: August 25, 2021

Record last verified: 2021-08

Locations

TW (1)