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3051 Background: Immunotherapy may produce durable responses in some patients. IMM-101, a systemic immunomodulator containing heat-killed Mycobacterium obuense (NCTC13365), can be combined with var...

336 Background: Immunotherapy is becoming established as an effective way of treating cancer. Immodulon Therapeutics is developing IMM-101, a heat-killed whole cell preparation of Mycobacterium obuense (NCTC 13365), which modulates systemic immune responses, as an adjunctive immunotherapy for pancreatic cancer. Methods: Patients with advanced pancreatic cancer and a WHO score of 0-2 were assigned randomly to receive IMM-101 (0.1 mL intradermal injection of 10 mg/mL) plus Gemcitabine (Gem) (1000 mg/m2for 3 consecutive weeks out of 4) or Gem alone. Per protocol, this could be continued to a 12-cycle maximum. The primary efficacy endpoint was overall survival (OS). Safety, tolerability and progression free survival (PFS) were also assessed. Results: A total of 110 patients were randomized, 75 to receive IMM-101 plus Gem and 35 Gem alone (ITT population). The PP population consisted of 63 and 35 patients, respectively. Conclusions were similar; here we report results of the PP analysis. Median OS was increased significantly by 29% to 7.2 months in the IMM-101 plus Gem group compared to 5.6 months in the Gem group (p=0.022; HR 0.60, 95% CI 0.38-0.94). Median PFS was increased significantly by 83% to 4.4 months in the IMM-101 plus Gem group compared to 2.4 months in the Gem group (p=0.003; HR 0.51, 95% CI 0.32-0.81). In the pre-defined sub-group of patients with metastatic disease (n=82), median OS was increased significantly by 70% to 7.5 months in the IMM-101 plus Gem group (n=54) compared to 4.4 months in the Gem group (n=28) (p=0.002; HR 0.46, 95% CI 0.28-0.76). A highly significant 91% increase in median PFS from 2.3 months in the Gem group to 4.4 months in the IMM-101 plus Gem group was observed (p5%) were asthenia 10.8% and abdominal pain 8.1% (both 2.9% in the Gem group). Conclusion: Clinically meaningful increases in OS and PFS were demonstrated with IMM-101. No additional burden of adverse events above those relating to chemotherapy or the underlying disease was observed. Clinical trial information: NCT01303172.

9050 Background: The cancer testis antigen NY-ESO-1 (ESO) has been evaluated as a biomarker and a therapeutic immunologic cancer target. Preliminary data from a phase I clinical trial of ESO and IS...

3018 Background: Since publication of the registration trial in 2010 (Hodi et al, NEJM 2010;363:711-23), real world use of ipilimumab (Ipi) in previously treated advanced melanoma patients has extended beyond the specific trial entry criteria of ECOG PS 0-1. We undertook a review of UK patients (pts) treated in the international EAP prior to European licensing of Ipi in August 2011, to compare real world survival outcomes. Methods: UK clinicians registered in the EAP provided anonymised data using pre-specified variable fields for all pts. The EAP stipulated pts should have previously treated, unresectable stage III or IV metastatic melanoma and receive Ipi 3 mg/kg, 3 weekly IV, for up to 4 cycles. Response using RECIST criteria was assessed 12 weekly. Grade ≥3 adverse events (AEs) using CTCAE v3.0 were collected. Results: To date, information on 162 pts has been received from 16 UK sites. Primary sites were: 78% cutaneous, 4% ocular, 1% mucosal, 17% unknown. 78% pts had M1c disease, 14% had brain metastases. No prior therapies ranged from 0-4, 72% pts received 1 prior therapy. Median age was 60 years, men>women (1.6:1). ECOG PS was: 38% 0, 47% 1, 14% 2, 1% 3. BRAF status was known in 38% cases and WT in 75% of these. 19% pts were on steroids at baseline. No cycles delivered was 4 in 52%, 3 in 13%, 2 in 16%, 1 in 17% pts. Most frequent reason for stopping early was clinical evidence of disease progression (71%), death (16%) or unacceptable AE (12%). 32% pts experienced a grade ≥3 AE, the most common being diarrhoea (13%) and fatigue (8%). Complete and partial responses were reported in 1% and 21% of treated pts. At median follow-up of 17 months, median progression free survival and overall survival (OS) were 2.8 and 5.7 months, 1 year OS was 30%. Comparing outcomes of various pt subgroups, the strongest prognostic factor for OS was ECOG PS at the start of treatment (p

8534 Background: In phase II trials, postoperative therapy with Canvaxin allogeneic melanoma cell vaccine plus Bacillus Calmette-Guerin (BCG) improved the survival of patients with stage IV melanoma. A multicenter, phase III placebo-controlled study was undertaken to investigate the vaccine’s efficacy. Methods: After complete resection of melanoma involving up to 5 distant sites, patients were randomized to treatment with BCG plus Canvaxin (BCG-Canvaxin) or BCG plus placebo (BCG-placebo). The primary endpoint was overall survival (OS); secondary endpoints were disease-free survival (DFS) and skin test responsiveness to the study agent. Results: Between May 1998 and April 2005, 496 patients were randomized. In April 2005, entry to the study was terminated due to low probability of demonstrating treatment differences. However, 256 patients from sites enrolled in a follow-up study were monitored until March 2010. Median OS and 5-year and 10-year rates of OS were 39.1 months, 43.3% and 33.3%, respectively, in the BCG-placebo group, versus 34.9 months, 42.5% and 36.4%, respectively, in the BCG-Canvaxin group (hazard ratio, 1.053; 95% confidence interval, 0.81 to 1.36; p=0.6964). Median DFS, 5-year DFS, and 10-year DFS were 7.6 months, 23.8% and 21.7%, respectively, for the BCG-placebo group, versus 8.5 months, 30.0%, and 30.0%, respectively, for the BCG-Canvaxin group (hazard ratio, 0.882; 95% confidence interval, 0.708 to 1.097; p=0.2595). Positive skin test results correlated with improved survival. Conclusions: BCG-Canvaxin was not superior to BCG-placebo, but the highly favorable long-term survival for combined groups indicates that complete metastasectomy should be considered as initial therapy for patients with resectable stage IV melanoma (ClinicalTrials.gov identifier: NCT00052156).

e13630 Background: Gemcitabine is the leading therapeutic for the treatment of pancreatic cancer, despite emergence of resistance. Understanding the mechanisms of gemcitabine resistance and discove...

e13155 Background: Docetaxel in combination with prednisone is approved for castrate-resistant metastatic prostate cancer (CRPC). However, docetaxel-based drug combinations may exhibit significant ...

e14635 Background: Lenalidomide is an immunomodulatory and anti-angiogenic agent that has demonstrated activity against a range of hematological malignancies. Despite evidence of direct anti-proliferative activity against hematological cells in vitro, there is no evidence of single agent direct activity against solid tumor cells in vitro. To take advantage of its known immune-enhancing properties alongside direct anti-tumor agents, lenalidomide is being advanced in solid tumor indications in combination with other agents. There are few data regarding the combination of lenalidomide and standard of care chemotherapeutic agents, such as gemcitabine. Methods: Here, we assess the effects of lenalidomide alone, and in combination with gemcitabine, on pancreatic cancer cell growth and survival, and the ability of lenalidomide to enhance the ability of human PBMC to kill allogeneic pancreatic tumor cells (BxPC3, PANC-1 and MiaPaCa) in a PBMC:tumor cell co-culture model. Results: Lenalidomide alone had no effect on the proliferation of pancreatic cancer cells (BxPC-3 and Panc-1) whereas gemcitabine had moderate anti-proliferative activity. With combination therapy there was clear synergistic enhancement of anti-proliferative activity in both cell lines and additive effects were observed in a BxPC-3 xenograft mouse model of pancreatic cancer. About 20% of tumor cells were sensitive to immune-mediated cell death and, for BxPC3, this was increased significantly in the presence of lenalidomide. Lenalidomide significantly and dose-dependently enhanced immune-mediated killing (both T and NK cells are required for tumor cell killing in this model). For PANC-1 and MiaPaCa, immune-mediated killing was also increased by lenalidomide, albeit non-significantly. Conclusions: These results suggest that, in addition to anti-angiogenic and other effects within the tumor microenvironment, lenalidomide may act as an immune adjuvant to enhance the recognition and apoptosis of tumor cells by host T and NK cells. These studies support the potential utility of lenalidomide in combination with chemotherapeutic agents, gemcitabine in particular, in the treatment of patients with solid tumors including pancreatic cancer. [Table: see text]

4213 Introduction: Gemcitabine is currently the standard treatment for patients (pts) with unresectable pancreatic cancer. It is beneficial but not associated with a high response rate. Retinoids are derivatives of vitamin A that have numerous effects on tumour cells, including inhibition of cell growth, and induction of differentiation and apoptosis. The effects of retinoic acid (RA):9-cis-RA or all-trans-RA (ATRA) on pancreatic tumour cell lines include inhibition of in vitro and in vivo growth, accompanied by differentiation, apoptosis, or both. Some studies evaluating combinations of RA and chemotherapeutic agents such as cisplatin, etoposide and paclitaxel have demonstrated synergy. Our data showed that pretreatment of pancreatic cell lines with RA followed by gemcitabine resulted in a dramatic increase in apoptosis. We therefore conducted a phase II pilot study of gemcitabine in combination with 13-cis RA in pts with locally advanced or metastatic carcinoma of pancreas. Methods: Study treatment was:...

4726 Background: We have shown previously that immunization with ONY-P1, a whole cell vaccine comprising 3 irradiated allogeneic prostate cancer cell lines, markedly increased time to disease progr...