Author of

• 12727

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  P3.13 - Poster Session 3 - SCLC (ID 202)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12734

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    P3.13-007 - Pilot trial of an adjuvant pentavalent vaccine for patients with small cell lung cancer (SCLC) (ID 2830)

    09:30 - 09:30  |  Author(s): G. Ragupathi
    • Abstract

    Background
    Despite initial responses to chemotherapy, SCLC typically progresses within a few months. Targeting residual disease has the potential to improve outcomes. A number of tumor specific glycolipid antigens have been identified and are potential targets for immune therapies. In a series of phase I clinical trials, vaccination with each of these antigens individually was safe and induced antibody responses in the majority of patients. Preclinical data indicate that combining these antigens will expand the immunogenicity across a broader array of SCLC tumor cells. We conducted this pilot trial to determine the safety and immunogenicity of a vaccine combining five of these antigens.

    Methods
    Patients with limited or extensive stage SCLC who have completed initial chemotherapy +/- thoracic or cranial irradiation with a maintained response are eligible. Vaccinations must start within 3-8 weeks of the last chemotherapy, and at least 1 week after radiation. Patients receive KLH-conjugates of GD2L, GD3L, Globo H, fucosyl GM1, and N-propionylated polysialic acid (30mcg each) plus OPT-821 adjuvant (150mcg) subcutaneously on weeks 1, 2, 3, 9, 20, and 32. One cycle of etoposide/platinum chemotherapy was administered in week 6. A significant immune response is defined as an antibody titer of ≥ 1:80 by ELISA against a given antigen or a ≥ 8 fold increase over baseline for patients with a detectable baseline titer. The vaccine would be deemed worthy of further study if >5 patients had an immune response to 3 or more antigens.

    Results
    Ten patients were treated, including 9 with extensive stage, 4 women, 7 with prior brain radiation. The number of vaccinations administered was: 1 (1pt), 3 (2), 4 (3), 5 (2), and 6 (2). Toxicity was limited to mild skin reactions. One patient was taken off study after he developed aphasia the day after the first vaccination; MRI brain was unremarkable and symptoms resolved spontaneously. No patients met the predefined criteria for immune response. Six patients had increases in IgM titers to 1-2 antigens. The median time to progression was 4 months. The two patients with the strongest IgM responses to Globo H and fucosyl GM1, and also the only IgG responses to fucosyl GM1, had progression of disease 7 and 9 months after starting the vaccines, and both progressed initially in the brain only.

    Conclusion
    The polyvalent vaccine is safe, but fewer patients than expected had a significant immune response, Two patients with immune responses experienced a longer than expected time to progression. A second cohort of patients is now receiving the vaccinations over a shorter period of time and without the added cycle of chemotherapy. Five out of 10 of those patients have been enrolled, and preliminary data will be available on those patients for the meeting. Following completion of this pilot trial, a multicenter randomized trial is planned. Supported by MabVax Therapeutics’s NIH grant R41 CA128363 and a grant from FAMRI.