P2.02-043 Randomized Ph II Trial of Allogeneic DPV-001 Cancer Vaccine Alone or with Adjuvant for Curatively-Treated Stage III NSCLC

Abstract

Tumor-derived autophagosomes (DRibbles®) are a novel cancer immunotherapy providing cross-protection against related tumors and efficacy against established tumors preclinically. We hypothesize efficacy is via presentation of short-lived proteins (SLiPs) and defective ribosomal products (DRiPs) normally not cross-presented by antigen-presenting cells (APCs). DRibble DPV-001 vaccine packages putative cancer antigens, including 13 from the NCI priority list and TLR 2, 3, 4, 7 and 9 agonist activity into microvesicles, with molecules targeting DRibbles to CLEC9A+ APCs. NSCLC overexpresses an average of 176 proteins found in DPV-001. Many of these antigens have single amino acid variants that may serve as immunogenic mimetopes, or altered peptide ligands. Pts completed curative-intent therapy for stage III NSCLC. Treatment: Induction cyclophosphamide; DPV-001 vaccine every 3 weeks x7; then every 6-weeks x4. Randomization was to DPV-001 alone (Arm A), or with an adjuvant; imiquimod (Arm B), or GM-CSF (Arm C). Peripheral blood mononuclear cells and serum were collected at baseline and at each vaccination. Serum was analyzed for >15 fold increased antibody responses to >9000 human proteins (ProtoArray) from baseline to week 12. 11 pts were to be randomized to each arm, with 15 more enrolled on the arm with the greatest number of >15 fold antibody responses. 13 pts were enrolled into the randomized phase I portion, when enrollment was stopped due to end of grant term. Arm A: 5 pts; B: 4; C: 4. Median Age: 60 (range 45-76); Male/Female: 6/7. Median vaccines administered: 6 (range 3-11); 2 pts still receiving treatment. Reasons for discontinuation: Disease progression (6); 2 toxicity (1 grade 3 dyspnea possibly related, 1 recurrent grade 1 migratory rash with pruritis, related); 1 noncompliance; 1 for elective surgery (unrelated). Other toxicities were grade 1/2; 1 additional grade 3 fatigue (possibly related). Analysis was limited due to small sample size. Median >15 fold antibody responses for Arm A: 8; B: 43.5; C: 50.5 (ranges 0-9; 41-46; 9-162, respectively). There was a significant difference in antibody response between Arms A and B (P=0.0001). Allogeneic DPV-001 vaccine administration was tolerable, and >15 fold antibody responses were documented in all but 1 pt. Greatest antibody responses were seen with vaccine/GM-CSF. For pts who may not respond to anti-PD1 due to lack of endogenous anti-tumor response, vaccination with DPV-001 could potentiate checkpoint inhibitors by inducing anti-tumor response. A combination DPV-001 vaccine with anti-PD1 study in advanced NSCLC is pending. NCT01909752, NCI sponsored trial R44 CA121612.