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Phase I study of peptide vaccine with chemotherapy in patients with unresectable colorectal cancer.

3067 Background: RNF43 is a cancer testis antigen expressed in colorectal cancer (CRC) but not in normal organs. RNF43-721 induces HLA A24 restricted cytotoxic T lymphocytes (CTL) against RNF43 expressed target. S-1/CPT-11 chemotherapy (CT) is reported to be obtained the similar result to FOLFOX or FOLFIRI as first-line for advanced CRC. We plan phase I study to evaluate the safety of different doses of RNF43-721 emulsified with Montanide ISA51 in combination with S-1/CPT-11 CT expecting synergistic effect.


METHODS
Inclusion criteria as follows: HLA A24 positive, pathological CRC, life expectancy > 3 months, WBC>3000/mm3, Hb>10mg/dl, Plt>75000/mm3, creatinine<1.2mg/dl, T. bil.<1.5mg/dl, AST, ALT<3x normal limits, written informed consent. Other malignancy, infection, treatment with steroids and immunosuppressive agents, and HBV, HCV, HIV infection are excluded. The study design is dose escalation of peptide (0.5, 1.0, 3.0 mg) with three patients' cohort. The study regimen is that oral administration of S-1 at 40 mg b.i.d. for 21 consecutive days followed by a 7-day rest period and intravenous infusion of CPT-11 at a dose of 80 mg on days 1 and 15 are performed with weekly subcutaneous injection of peptide vaccine. Two courses are study periods and there is no restriction of therapy after study. Primary endpoint is safety and secondary are CTL, objective response rate and TTP.


RESULTS
Twelve patients (pts) were enrolled and 3 pts canceled treatment due to patient's proposal. In 9 evaluable pts, median age of pts with 7 males and 2 females was 61. Standard chemotherapy for CRC were failed in 8 pts. Systemic toxicities were observed in one pt with grade 2 and others were grade 1. Skin reactions were occurred in 7 pts. No pts were obtained CR and PR, 6 pts were SD and 3 were PD. CTL response was observed in 5 pts. TTP was calculated as 204 days.


CONCLUSIONS
Treatment with peptide vaccine and S-1/CPT-11 CT was well tolerated. These results encourage further clinical trials of peptide vaccine with standard CT for advanced CRC. No significant financial relationships to disclose.