Phase II Study of S-488410 to Treat Non-small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
The investigators identified three cancer-testis antigens, as targets for cancer vaccination against lung cancer. In this clinical study, the investigators examine using a combination of three peptides from these three antigens (S-488410) the safety, immunogenicity, and antitumor effect of vaccine treatment for advanced non-small cell lung cancer patients.

Detailed Description
-----------------
The purpose of this study is to evaluate the clinical efficacy and safety of S-488410 for advanced non-small cell lung cancers who failed to standard therapy. The investigators previously identified three novel HLA-A*2402-restricted epitope peptides, which were derived from three cancer-testis antigens, as targets for cancer vaccination against lung cancer. In this phase II trial, we examine using a combination of these three peptides the safety, immunogenicity, and antitumor effect of vaccine treatment for HLA-A*2402-positive advanced small cell lung cancer patients who failed to standard therapy.

Official Title
-----------------
Phase II Study of Peptide Cancer Vaccine S-488410 to Treat Advanced Non-Small Cell Lung Cancer

Conditions
-----------------
Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
-----------------
* Drug: S-488410


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Advanced NSCLC that cannot undergo curative surgery. Patients that are refractory to standard chemotherapy or cannot be treated with further therapy due to severe adverse effects of chemotherapy. Histologically diagnosed NSCLC. Clinical efficacy can be evaluated by radiologic methods within 4 weeks prior to receiving treatment. ECOG performance status 0-2 within 2 weeks prior to receiving treatment. Life expectancy > 3 months. Age between 20 to 79 Male or Female. In patients or out patients. Able and willing to give valid written informed consent. Exclusion Criteria: Other malignancy requiring treatment radiation, immunotherapy, hyperthermia, or surgery. Active and uncontrolled infectious disease Active and uncontrolled hepatic dysfunction, kidney dysfunction, cardiac disease, or lung disease (i.e. interstitial pneumonia). Autoimmune disease. HIV-Ab or antigen positive Prior anti-cancer therapy within 4 weeks Laboratory values as follows: 2000<mm3 < WBC < 15000/mm3, Platelet count < 50000/mm3, Asparate transaminase > 5 X cutoff value, Alanine transaminase > 5 X cutoff value, Total bilirubin > 3 X cutoff value, and Serum creatinine > 3X cutoff value. Patients knows HLA-A type. Breastfeeding and Pregnancy (woman of child bearing potential) Refusal of pregnancy conception. Treated with S-488401, S-488402, or S-488403. Treated with other investigational drug within 3 months prior to receiving S-48810 treatment. Decision of nonenrollment of the patients by principal investigator or physician-in-charge from the view point of patient's safety.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 79 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: S-488410<br> | Drug: S-488410<br>* In multicenter HLA-blinded open study, patients will be vaccinated subcutaneously once a week with S-488410 (S-488401, S-488402, S-488403, 1mg each).<br>* Other names: S-488410 (S-488401, S-488402, S-488403).;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of difference in overall survival after vaccination therapy between HLA-A 24:02 and non-HLA-A 24:02 patients. |  | Participants will be followed for the duration of vaccination therapy, an expected average of more than 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CTL response between HLA-A24:02 and non-HLA-A24:02 |  | Participants will be followed for the duration of vaccination therapy, an expected average of more than 1 year. | 
| PFS and ORR between HLA-A24:02 and non-HLA-A24:02 |  | Participants will be followed for the duration of vaccination therapy, an expected average of more than 1 year. | 
| PFS and OS between CTL response positive and negative |  | Participants will be followed for the duration of vaccination therapy, an expected average of more than 1 year. | 
| Safety and tolerability: Number of Adverse Events with information of disease, grade and incidence |  | Participants will be followed for the duration of vaccination therapy, an expected average of more than 1 year. | 
| Identification of biomarkers for efficacy and safety that are mentioned above |  | Participants will be followed for the duration of vaccination therapy, an expected average of more than 1 year. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cancer vaccine, HLA-A*24:02, lung cancer, CTL