Neoantigen-primed DC Vaccines Therapy for Refractory Lung Cancer

A Phase I Study on the Safety and the Efficacy of Personalized Neoantigen-primed Dendritic Cell Vaccines for Refractory Lung Cancer

Various of immunotherapies are now widely applied in the treatment of lung cancer. Neoantigens arising from the mutations of the tumor genome expressed specifically on the tumor cell instead of normal cells, suggesting that vaccines targeting neoantigens should generate a highly tumor-specific response with minimal off-target effects. Neoantigens are highly suitable for the development of cancer vaccines. The study aims to evaluate the safety and efficacy of neoantigen-loaded dendritic cell (DC) vaccines for refractory lung cancer.

Study Overview

• Status: Unknown
• Conditions: Carcinoma, Non-Small Cell Lung; Carcinoma, Small Cell Lung
• Intervention / Treatment: Biological: Neoantigen loaded DC vaccine

Detailed Description

Cancer genome research has exploded benefits from the application of modern high-throughput genome sequencing in the past few years. Since usually there are no common antigens expressed on the surfaces of different kinds of tumors, neoantigens which expressed specifically in the individual tumor are chosen to establish tumor-specific vaccines.

30 patients with refractory lung cancer would be enrolled and undergo tumor resection if all requirements are met. The whole-exome sequencing and the bioinformatic analysis of the resected specimens would be performed to identify the neoantigens. Then, candidate neoantigens would be synthesized to pulse the matured DC cells. Neoantigen-primed DC vaccines are provided to the corresponding patients. Each patient would be vaccinated 6 times in total, one shot per week.

Patients enrolled would undergo the schemed follow-up, one time per three months. The side effects, overall survival, and progress-free survival would be recorded. At the end of the research, the safety and efficacy of neoantigen DC vaccines for refractory lung cancer would be evaluated.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518020
      • Shenzhen People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 years ≤ 70 years at the time of informed consent
• Signed informed consent to be provided
• pathologically confirmed lung cancer
• failed in previous standard chemotherapy and targeted therapy
• Life expectancy not less than 90 days
• Karnofsky performance status 0-1
• adequate organ functions

Exclusion Criteria:

• Actively infectious condition including hepatitis
• Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
• Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
• Active systemic infections, coagulation disorders or any other active major medical illnesses.
• Patients who are receiving any other investigational agents.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vaccinated group; Neoantigen loaded-DC vaccination will be performed with 6 doses in total, once per week, adjacent lymph-node injection.	Biological: Neoantigen loaded DC vaccine; Patients will be vaccinated with autologous mature dendritic cells loaded with neoantigen, DC vaccine will be injected subcutaneously 6 times, once a week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety]	Safety of personalized neoantigen vaccine will be measured by the number of subjects experiencing each type of adverse event. Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0.	3 months after the last vaccination injection
Immunogenicity of neoantigen-primed DC Vaccines	Immunogenicity of the DC vaccine will be measured to detect changes of neoantigen-specific T cells by flow cytometry.	once per three month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	The objective response rate is equal to the proportion of participants achieving a best overall response of partial response or complete response (PR + CR). Percentage of Participants Achieving a Stable Disease (SD) or a confirmed CR or PR (Disease Control Rate) Participants achieved disease control if they had a best overall response of CR, PR or SD.	once per three months
Overall Survival (OS)	OS was defined as the time in months from the date of randomization to the date of death from any cause. For participants not known to have died as of the cut-off date, OS was censored at the last known date alive.	through study completion, an average of 1 year
Progression-free Survival (PFS)	PFS:duration of time from start of treatment to time of progression or death, whichever occurs first.	up to 24 months after last dose of vaccine

Collaborators and Investigators

• Sponsor: Shenzhen People's Hospital
• Investigators: Principal Investigator: Lili Ren, Ph.D., Shenzhen People's Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2019
• Primary Completion (Anticipated): June 30, 2020
• Study Completion (Anticipated): December 30, 2020

Study Registration Dates

• First Submitted: March 7, 2019
• First Submitted That Met QC Criteria: March 10, 2019
• First Posted (Actual): March 12, 2019

Study Record Updates

• Last Update Posted (Actual): March 12, 2019
• Last Update Submitted That Met QC Criteria: March 10, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Immunotherapy; Neoantigen; Dentritic cell vaccine; Refractory lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma; Small Cell Lung Carcinoma; Carcinoma, Small Cell
• Other Study ID Numbers: ShenzhenPH BTR-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No