Pilot trial with a tetravalent conjugate vaccine against small cell lung cancer

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DESCRIPTION (provided by applicant): This Phase 1 STTR application is for a pilot clinical trial of an antibody inducing tetravalent vaccine against SCLC. Its foundation is 30 years of studies during which time 1) vaccine design for optimal antibody responses against cancer cell surface antigens was determined, 2) the benefit of immunization in the minimal disease setting where circulating tumor cells and micrometastases are the primary targets was demonstrated in preclinical studies, 3) the antigens expressed by the common cancers were defined and the 4 antigens relevant for a SCLC vaccine identified, 4) the SCLC tetravalent vaccine was selected as the most promising for testing in a randomized Phase 2 trial, 5) the safety and immunogenicity of monovalent vaccines against these four antigens was confirmed and, the optimal dose of each vaccine in patients in the post chemotherapy adjuvant setting was determined, and 6) technology for vaccine production was successfully transferred to a contract GMP facility (Althea Technologies, Inc.) so that conjugates could be prepared for a multicenter Phase 2 clinical trial. The primary endpoints of the proposed pilot trial are safety and immunogenicity. Since the individual conjugates in this tetravalent vaccine were prepared under contract by GMP facilities instead of at MSKCC as in the past, and will be vialed and administered together rather than individually to separate patients, the issues of safety and immunogenicity are not trivial. If this GMP grade tetravalent vaccine proves safe and immunogenic in the pilot trial to be supported by this Phase 1 application, a Phase 2 STTR application to support the randomized, placebo-controlled Phase 2 trial will be submitted. Administered antibodies and antibodies induced by the tetravalent vaccine proposed here against small cell lung cancer (SCLC) cell surface antigens are ideally suited for eradication of free SCLC cells and micrometastasis. If antibodies of sufficient titer can be induced against these antigens to eliminate tumor cells from the blood and to eradicate micrometastasis, this would dramatically change our approach to treating the SCLC patient. Establishment of new metastasis would no longer be possible so more aggressive local therapies including surgery or radiation therapy of minimal known residual metastasis might result in long term control of even metastatic SCLC.