Safety Study of Peptide Cancer Vaccine To Treat HLA-A*02-positive Advanced Non-small Cell Lung Cancer

The investigators previously identified three novel HLA-A*0201 or HLA-A*0206-restricted epitope peptides, which were derived from a cancer-testis antigen, URLC10, as targets for cancer vaccination against lung cancer. In this phase I trial, the investigators examine using a combination of these three peptides the safety, immunogenicity, and antitumor effect of vaccine treatment for HHLA-A*0201 or HLA-A*0206-positive advanced non-small cell lung cancer patients who failed to standard therapy.

• HLA-A*0201 or HLA-A*0206-restricted URLC10 peptides (Biological), also known as URLC10: Escalating doses of every peptide will be administered by subcutaneous injection on days 1, 8, 15 and 22 of each treatment cycle. Planned doses of peptides are 1.0mg, 2.0mg and 3.0mg.

Primary outcomes

• Evaluation of safety (NCI CTCAE version3): the number of adverse events of vaccination therapy. [2 months]
• Evaluation of tolerability (maximum tolerated dose, MTD and dose limiting toxicity, DLT) for the determination of the recommended dose for next phase trial. [2 months]

Secondary outcomes

• Immunological responses: Peptides specific CTL, Antigen cascade, Regulatory T cells, Cancer antigens and HLA levels. [2 months (every time point(s) at which each course is completed)]
• Evaluation of clinical efficacy: Objective response rate (RECIST1.1), Tumor markers, Overall survival, Progression free survival. [2 months (every time point(s) at which each course is completed)]

Sex: All, ages: 20 Years to 85 Years

Inclusion Criteria:

1. NSCLC that can not undergo curative surgery and treatment, and is refractory to standard chemotherapy and radiotherapy
2. ECOG performance status 0-2
3. Age between 20 to 85
4. Clinical efficacy can be evaluated by some methods
5. No prior chemotherapy, radiation therapy, hyperthermia or immunotherapy within 4 weeks
6. Life expectancy > 3 months
7. Laboratory values as follows 1500/mm3 < WBC < 15000/mm3 Platelet count > 75000/mm3 Asparate transaminase < 3 X cutoff value Alanine transaminase < 3 X cutoff value Total bilirubin < 3 X cutoff value Serum creatinine < 2X cutoff value
8. HLA-A*0201 or HLA-A*0206
9. Able and willing to give valid written informed consent

Exclusion Criteria:

1. Active and uncontrolled cardiac disease (i.e. coronary syndromes, arrhythmia)
2. Myocardial infarction within six months before entry
3. Breastfeeding and Pregnancy (woman of child bearing potential)
4. Active and uncontrolled infectious disease
5. Concurrent treatment with steroids or immunosuppressing agent
6. Other malignancy requiring treatment
7. Non-cured traumatic wound
8. Decision of unsuitableness by principal investigator or physician-in-charge

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• Yataro Daigo, MD, PhD, Principal investigator, Department of Medical Oncology, Shiga University of Medical Science