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7 Background: The IRX-2 biologic is an injectable immunotherapy containing cytokines derived from stimulated lymphocytes. In preclinical models, IRX-2 activates T-cells, natural killer (NK) cells, macrophages, and dendritic cells, and facilitates maturation of antigen-presenting cells. Stromal tumor-infiltrating lymphocytes (sTILs) are associated with improved outcomes in early stage breast cancer (ESBC), and neoadjuvant IRX-2 increased TILs in a head/neck squamous cell carcinoma trial. We conducted a phase Ib trial to evaluate the feasibility/activity of IRX-2 in ESBC. Methods: Beginning 21 days prior to surgical resection, enrolled operable patients with stage I-III ESBC received the pre-operative IRX-2 regimen consisting of a single low dose of cyclophosphamide (300 mg/m2 to facilitate T-regulatory cell depletion), followed by 10 days of subcutaneous peri-areolar injections of IRX-2 into the affected breast (1 mL × 2 at tumor axis and at 90°). Endpoints were feasibility (primary), sTIL count (secondary), and immune monitoring by flow cytometry and immune transcriptome analysis (Nanostring PanCancer Immune Panel). Results: As of October 2017, 12 patients are enrolled and evaluable. All patients received all planned injections with no treatment-related surgical delays, complications, or grade III/IV toxicities. Treatment was associated with a mean 52% relative increase in sTILs (range –25% to +166%, p = 0.02). RNA expression profiling revealed the greatest increases in Th1 cell signature (mean +28.5%, range -5.3% to +283%), but also increases in CD8+, NK, and DC signatures. PDL1 RNA expression increased in 10/12 patients (mean +131.5%, range –83% to +1112%). In blood, increases in T-cell activation markers (ICOS, HLADR, and CD38) and T-reg depletion were observed at 1-month follow-up. Conclusions: Peri-lymphatic IRX-2 was well tolerated with preliminary evidence of sTIL recruitment, PDL1 upregulation, and peripheral lymphocyte activation. Study enrollment is ongoing, including patients for a pre-neoadjuvant-chemotherapy triple-negative ESBC cohort. Clinical trial information: NCT02950259.

e14578Background: Survivin is strongly expressed in tumors of about 60% of diffuse large B-cell lymphoma (DLBCL) patients. DPX-Survivac contains survivin HLA class I peptides in a novel formulation...

e14577Background: Survivin is an important protein that regulates apoptosis, proliferation, and angiogenesis of tumors. Increased expression of survivin in various tumors correlates with progressio...

PURPOSE The purpose of this review was to assess the outcome of patients with non-Hodgkin's lymphoma (NHL) who achieve an incomplete or slow response to front-line chemotherapy and to determine whether salvage treatment with intensive combination chemotherapy with or without autologous bone marrow transplantation (ABMT) is successful in such patients. METHODS A comprehensive literature search of studies using combination chemotherapy for the front-line therapy of advanced-stage intermediate- and high-grade NHL and for salvage therapy of patients with a partial response (PR) was reviewed. RESULTS The median survival duration of patients with a PR ranged between 5 to 14 months, while the median survival duration of patients with a complete response (CR) was not reached in many studies. For patients in CR, the probability of survival at 24 months ranged between 0.79 to 1, while for patients in PR it ranged from 0 to 0.31. The rapidity of a response to front-line therapy was often found to be of prognostic importance. Patients who relapsed after a PR to front-line therapy had similar outcomes to intensive salvage therapy as those who relapsed after a CR. ABMT performed immediately after a PR to induction therapy, before progressive disease occurred, resulted in high CR rates in nonrandomized studies. CONCLUSION Patients with aggressive NHL who experience a PR or who respond slowly to front-line chemotherapy have a poor prognosis. Early introduction of dose-intensive salvage therapy before the development of progressive disease may benefit patients with a PR and requires testing in randomized clinical trials.

3072 Background: Survivin is important in apoptosis, proliferation, and angiogenesis. High expression has been linked to progression and drug resistance. DPX-Survivac vaccine (DPX) contains a mix o...

5555 Background: Survivin plays a key role in apoptosis, proliferation and angiogenesis. It is overexpressed in 90% of epithelial OC making it an attractive target. Increases in expression have been correlated with progression and drug resistance. DPX-Survivac is a vaccine containing a mix of survivin HLA class I peptides designed to evoke a cytotoxic T cell response against survivin. This Phase I/Ib de-escalation study reports the safety and immune potency of DPX-Survivac in combination with metronomic low dose oral cyclophosphamide (CPA) in OC. Methods: 30 Stage IIc-IV advanced or recurrent OC patients (pts) with no evidence of disease progression post chemotherapy were enrolled. Dose limiting toxicities (DLT) were defined as ≥gd3 AEs, ≥gd2 allergic or autoimmune reactions by CTCAE v4.03. Immune correlates (MDSCs; T regs; B cells) and vaccine induced T cell immunity (ELISpot; tetramer analysis; multi-parametric intracellular cytokine staining) were assessed in purified PBMC and blood. Clinical response ...

3030 Background: Survivin, a protein involved in regulation of apoptosis, is highly expressed in many tumor types and has reported prognostic value. DPX-Survivac is a cocktail of survivin HLA class I peptides (A1, A2, A3, A24 and B7) formulated in the novel adjuvanting vaccine platform DepoVax. A phase I study examined the safety and immune potency of DPX-Survivac in combination with cyclophosphamide in ovarian cancer patients. Methods: 18 of 19 advanced ovarian cancer patients treated with platinum chemotherapy and showing no disease progression completed their vaccine therapy. Cohort A (6 pts) received three 0.5 mL vaccine injections 3 weeks apart; cohorts B and C (6 pts each) received three 0.1 mL or 0.5 mL vaccine injections in combination with metronomic low dose oral cyclophosphamide. Adverse events were assessed using CTCAE v4.0. Blood was collected to study immune function (MDSCs, T regs and B cells) and vaccine-induced T cell immunity (ELISpot, tetramer analysis and multi-parametric intracellular cytokine staining). Repeated measures of immunity at baseline and after 1, 2 and 3 injections were analyzed using a general linear model. Results: DPX-Survivac was well tolerated with no significant systemic AEs. Local injection AEs occured in all patients. Grade 3 local reactions occured in 3 patients (1 pt in B and 2 pts in C). 11 of 12 patients receiving the combination therapy produced immune responses by at least 2 assays, generally established with one or two vaccinations and increased or maintained with boosters. A dose response was observed, with cohort C patients producing significantly higher magnitude responses (C vs B, P=.013). Low dose cyclophosphamide significantly enhanced the 0.5 ml dose (C vs A, P=.015). Notably, antigen specific CD8 T cells were detected ex vivoi n PBL’s using tetramers and further characterized as polyfunctional by multi-parametric ICS, suggesting a robust immune response. Conclusions: DPX-Survivac is well tolerated and immunogenic. Immune modulation with low dose oral cyclophosphamide can dramatically enhance the immunogenicity of this vaccine. The efficacy of the proposed DPX-Survivac vaccine therapy needs to be tested in a randomized phase II study. Clinical trial information: NCT01416038.

2588 Background: To increase the efficacy of peptide cancer vaccines, we developed a novel vaccine platform called DepoVax, an adjuvanted water-free depot formulation with the ability to generate enhanced immune responses. Naturally processed HLA-A2 restricted peptides that are selectively presented by breast, ovarian and prostate cancer cell lines, but not by normal HLA-A2+ cells, were used as antigens with a proprietary adjuvant and a T helper peptide epitope to create a therapeutic cancer vaccine, DPX-0907. Methods: A phase I clinical study was designed to examine the safety and immune activating potential of DPX-0907 in advanced stage breast, ovarian and prostate cancer patients. A total of 23 late stage cancer patients were recruited and were divided into two dose volume cohorts in a three immunization clinical protocol. Results: DPX-0907 proved to be safe with no serious adverse effects related to the vaccine reported. Of those evaluable for immunogenicity, all breast cancer patients (3/3), most of ovarian (5/6) and one third of prostate (3/9) cancer patients demonstrated immune response to one or more of seven antigenic peptides, resulting in a 61% response rate. Immune responses correlated with achievement of CR, PR or SD to last treatment. No difference in immune response rate or magnitude was seen between the two dose groups. DPX-0907 displayed strong immune induction potential, with 73% of immune responders showing responses with just one dose of vaccine. In 83% of responders, immune responses were detected at ≥2 time points post vaccination and 64% had a persistent immune response at one month post last vaccination. Immune monitoring showed peptide-specific CD8 T cells, and these T cells were able to secrete multiple Th1 cytokines indicating their multifunctionality, a feature attributable to cells that mediate protective responses. Conclusions: These data support the ability of DPX-0907 to elicit Th1 dominated, specific immunity and support the rationale for further testing in immunologically competent cancer patients. The novel DepoVax formulation may promote multifunctional memory responses with peptides from other tumor associated antigens.

e13050 Background: Immunovaccine Inc. (IMV) has developed a novel liposome-in-oil depot vaccine platform called DepoVax (DPX), which increases the potency of peptide-based vaccines. DPX-0907 is a D...

8098 Background: CNS relapse following initial treatment of DLBCL is an uncommon but fatal complication. The addition of rituximab improves the clinical outcome dramatically, but its influence on C...