Author of

• 10801

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  P1.11 - Poster Session 1 - NSCLC Novel Therapies (ID 208)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10825

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    P1.11-024 - A phase I/II randomized trial using GM-CSF-producing and CD40L-expressing bystander cell line (GM.CD40L) vaccine plus or minus CCL21 in stage IV lung adenocarcinoma: Updated results (ID 1878)

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

    Background
    Background: The GM.CD40L vaccine, an allogeneic tumor cell-based vaccine generated from a human bystander cell line which secretes GM-CSF and expresses CD40L on the surface (GM.CD40L), was developed by our team. It serves to recruit and activate dendritic cells. The mature dendritic cells in turn travel to regional lymph nodes and help to activate T cells which result in systemic tumor cell killing. CCL21 is a chemokine which serves to enhance recruitment of T cells and enrich T cell responses. In NSCLC mouse model, the vaccine combination of GM.CD40L plus CCL21 demonstrated additive effects.

    Methods
    Methods: We conducted a phase I/II randomized study to evaluate the GM.CD40L (Arm A) vs. GM.CD40L.CCL21 (Arm B) vaccine in patients with lung adenocarcinoma who had failed first-line therapy. Primary endpoints were safety and tolerability of Arm B in phase I and 6 month progression-free survival (PFS) in phase II; secondary endpoints included anti-tumor immune responses and T-cell responses by ELISpot assay on PBMC. Immune-related response criteria (irRC) determined discontinuation from study treatment at the discretion of the PI/treating physician. Intradermal vaccines were administered in the bilateral axilla and groin every 14 days for 3 doses and then monthly for 3 doses. A two-stage minimax design was used. Survival probabilities over time in each treatment group were estimated using the method of Kaplan and Meier.

    Results
    Results: Between 4/2012 and 4/2013, phase 1 enrolled 3 patients on GM.GD40L.CCL21, while Arm A enrolled 17 and Arm B enrolled 14 patients. The baseline characteristics, including those in phase I are as follows: median age: 66/68 years, females: 50%/50%, PS1: 64.7%/76.5%, median prior regimens: 2.5/3 for Arm A vs. Arm B, respectively. No DLT’s were observed during phase 1. The most common toxicities for Arm A vs. Arm B were injection site reaction (70.6%/70.6%), fatigue (29.4%/41.2%), anorexia (23.5%/29.4%), and pain in extremity (5.9%/5.9%). Median PFS for Arm A vs. B was 1.9 vs. 4.4 months (p=0.10). All patients who remained on study per MD discretion/irRC, did ultimately demonstrate further progression on subsequent imaging. Treatment was discontinued in all of those patients. In Arm A versus Arm B, stable disease was 4/8 and progressive disease was 8/8, respectively. The disease control rate (DCR) for Arm B compared with Arm A was 50% versus 33%, respectively. ELISpot assay for immune responses and flow cytometry studies on PBMCs are underway.

    Conclusion
    Conclusion: GM.CD40L plus CCL21 chemokine is well tolerated. The phase II trial including further immune response assays collected pre and post vaccine are underway and updated results will be presented.