Clinical trial NCT03871205: Neoantigen-primed DC Vaccines Therapy for Refractory Lung Cancer
Official title: A Phase I Study on the Safety and the Efficacy of Personalized Neoantigen-primed Dendritic Cell Vaccines for Refractory Lung Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Carcinoma, Non-Small Cell Lung
Carcinoma, Small Cell Lung
Keywords: Neoantigen
Dentritic cell vaccine
Immunotherapy
Refractory lung cancer
Lead sponsor: Shenzhen People's Hospital
Sponsor class: OTHER
First posted: 2019-03-12
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety]
timeFrame: 3 months after the last vaccination injection
measure: Immunogenicity of neoantigen-primed DC Vaccines
timeFrame: once per three month
Secondary outcomes:
measure: Objective Response Rate
timeFrame: once per three months
measure: Overall Survival (OS)
timeFrame: through study completion, an average of 1 year
measure: Progression-free Survival (PFS)
timeFrame: up to 24 months after last dose of vaccine
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
state: Guangdong
Study officials:
affiliation: Shenzhen People's Hospital
name: Lili Ren, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: