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B. Boulmay
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P3.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 214)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.03-016 - Randomized ph II Trial of Cyclophosphamide with Allogeneic DPV-001 Cancer Vaccine Alone or with Adjuvant for Curatively-Treated Stage III NSCLC (ID 3028)
09:30 - 09:30 | Author(s): B. Boulmay
- Abstract
Background:
Tumor-derived autophagosomes (DRibbles) are a novel dendritic cell-targeted cancer immunotherapy that preclinically provides cross-protection against related tumors and efficacy against established tumors. We hypothesize DRibbles’ efficacy is due to presentation of stabilized tumor-derived short-lived proteins (SLiPs) and defective ribosomal products (DRiPs) normally not processed or presented by antigen presenting cells (APCs). SLiPs and DRiPs provide a potential pool of tumor antigen to which the host may not be not tolerant. This DRibble DPV-001 vaccine packages several hundred putative cancer antigens, including 13 antigens from the NCI list of priority antigens and agonist activity for TLR 2, 3, 4, 7 and 9 into stable double membrane microvesicles which have surface molecules targeting DRibbles to CLEC9A+ APCs (the most effective APC at cross-priming immunity). DPV-001 contains an average of 176 proteins from genes overexpressed in NSCLC patient tumors. Many of these putative cancer antigens have single amino acid variants that may serve as mimetopes, or altered peptide ligands, and thereby increase immunogenicity.
Methods:
Pts are eligible after completion of standard curative-intent therapy for stage III NSCLC. Pts receive induction cyclophosphamide, then 7 DPV-001 vaccines at 3-week intervals. The first vaccine is given intranodally; subsequent vaccines intradermally. Pts are randomized to receive DRibble alone, or with adjuvant imiquimod or GM-CSF. Peripheral blood mononuclear cells and serum are collected at baseline and at each vaccination. Serum from baseline and week 12 is analyzed for antibody response to >9000 human proteins (ProtoArray). When available, multispectral Immunoprofiling is performed on tumor to evaluate pre-existing immunity and Human Exome Capture and Next Generation Sequencing is done on tumor (100x coverage) and matched normal tissue. Tumor somatic mutations are compared to DPV-001 to identify shared non-synonymous single nucleotide variations (nsSNVs) with the vaccine, including mutations with potential increased immunogenicity. Pts will be analyzed comparatively for strong antibody responses (>15 fold increase in titer). 11 pts will be randomized to each arm, with 15 more enrolled on the arm with greatest number of strong antibody response. 8 pts have been enrolled, and accrual is ongoing.
Results:
Not applicable
Conclusion:
Not applicable
