On November 09, 2015 Aduro Biotech, Inc. (Nasdaq:ADRO) reported five posters highlighting ongoing clinical trials and pre-clinical programs investigating its novel immunotherapies in development for the treatment of cancer were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting held in National Harbor, Maryland last week (Press release, Aduro BioTech, NOV 9, 2015, View Source;p=RssLanding&cat=news&id=2110402 [SID:1234508127]).

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In a poster presented on Saturday, November 7, 2015 by Nitya Nair, Ph.D., scientist at Aduro, updated safety and efficacy data were shared from the Phase 2a clinical trial of Aduro’s novel immunotherapy CRS-207 in combination with GVAX Pancreas in patients with metastatic pancreatic cancer. Seven patients treated with this regimen survived for over three years, with one patient continuing to receive the combination regimen. In addition, the poster highlighted key biomarker findings in 38 patients from the 93-patient trial which demonstrated a statistically significant correlation between levels of certain immune cells in the peripheral blood and overall survival. Specifically, the data showed elevated subsets of CD8+ immune T cells at baseline and at seven weeks after treatment initiation resulted in better performance outcomes. Conversely, an increase in subsets of certain myeloid cells (CD14+) at the same time points was associated with worse outcomes.

In another poster presented by Jeremy Foote, Ph.D. D.V.M., at Johns Hopkins University School of Medicine, encouraging preclinical results demonstrated that direct intratumoral injection of Aduro’s human STING-activating CDN immunotherapy in a model of HER2+ breast cancer resulted in complete eradication of the injected tumor as well as distant untreated tumors. In addition, the responses observed were durable, showing long lasting immunologic memory and anti-tumor protection when CDN-treated mice were re-challenged with HER2+ breast cancer tumor cells. In a much more challenging tumor model that is profoundly tolerant for the HER2 tumor antigen and with greater similarity to advanced cancer patients, treatment combining a single intratumoral injection of CDN with cyclophosphamide and anti-PD-L1 immune checkpoint antibodies resulted in pronounced inhibition of tumor growth. Together, these results demonstrate that activation of the STING pathway in the tumor microenvironment by the direct injection of Aduro’s proprietary CDNs results in the development of tumor antigen-specific immunity and tumor regression.

Separately, three additional posters were presented at the SITC (Free SITC Whitepaper) meeting that provide details on the ongoing trials, namely the Phase 2b STELLAR trial in pancreatic cancer, an expanded cohort in a Phase 1b trial in mesothelioma and a Phase 1 trial in grade 3/4 gliomas, including glioblastoma multiforme.

The STELLAR (Safety and Therapeutic Efficacy of Live-attenuated Listeria/GVAX with Anti-PD1 Regimen) poster highlighted the randomized, controlled trial that now has an increased enrollment target of 102 adult patients with metastatic pancreatic cancer who have failed one prior chemotherapy regimen for metastatic disease. Patients are randomized equally to one of two arms: Arm A with CRS-207/GVAX Pancreas vaccine and nivolumab or Arm B with CRS-207/GVAX Pancreas vaccine. The primary objective of this study is to compare the overall survival of patients in Arm A and Arm B. Secondary endpoints include evaluation of clinical and immune response and safety. For more information, please visit ClinicalTrials.gov (Identifier: NCT02243371). With the increased enrollment target, Aduro now expects enrollment to be completed in the second half of 2016 and continues to expect interim data in the second half of 2016.

A separate poster highlighted an expansion cohort in the Phase 1b clinical trial of CRS-207 in combination with chemotherapy. In this second cohort, eligible patients will first receive low-dose cyclophosphamide (Cy) one day prior to receiving two prime vaccinations with CRS-207 two weeks apart, followed by up to six cycles of standard-of-care pemetrexed and cisplatin chemotherapy three weeks apart and two CRS-207 boost vaccinations three weeks apart. Cy has been added to the regimen for the second cohort of patients to evaluate whether the triplet regimen improves tumor responses by reducing regulatory T-cells with Cy. Clinically stable patients will continue to receive Cy/CRS-207 maintenance vaccinations every eight weeks and are followed every eight weeks until disease progression. Objectives of the study are safety, immunogenicity, objective tumor responses and tumor marker kinetics.

Another poster provided an overview of the investigator-sponsored Phase 1 trial to evaluate the safety and immunogenicity of Aduro’s ADU-623 in grade 3/4 gliomas (including anaplastic astrocytomas and glioblastoma brain cancers). This is a dose-escalation trial enrolling up to 18 patients. The primary objective of the trial is to identify the maximum tolerated dose and characterize the safety profile of the ADU-623 vaccine in patients with treated and recurrent grade 3/4 astrocytomas. For more information, please visit ClinicalTrials.gov (Identifier: NCT01967758).

About CRS-207
CRS-207 is one of a family of product candidates based on Aduro’s live-attenuated, double-deleted (LADD) Listeria monocytogenes immunotherapy platform that induces a potent innate and T cell-mediated adaptive immune response. CRS-207 has been engineered to express the tumor-associated antigen mesothelin, which is over-expressed in many cancers including mesothelioma and pancreatic, non-small cell lung, ovarian, endometrial and gastric cancers.

About Cyclic Dinucleotide (CDN)
Aduro’s proprietary CDN product candidates are synthetic small molecule immune modulators that are designed to target and activate a receptor known as the Stimulator of Interferon Genes, or STING. The STING receptor is generally expressed at high levels in immune cells, including dendritic cells. Once activated, the STING receptor initiates a profound innate immune response through multiple pathways, inducing the expression of a broad profile of cytokines, including interferons and chemokines. This subsequently leads to the development of an effective tumor antigen-specific T cell adaptive immune response.

About LADD and ADU-623

LADD is Aduro’s proprietary platform of live-attenuated double-deleted Listeria monocytogenes strains that have been engineered to induce a potent innate immune response and to express tumor-associated antigens to induce tumor-specific T cell-mediated immunity. ADU-623 is engineered to express EGFRvIII and NY-ESO-1, which are expressed in glioblastoma and other cancers.

About Aduro

On November 9, 2015 DelMar Pharmaceuticals, Inc. (OTCQX: DMPI) ("DelMar" and the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported that its abstract entitled, "Phase I/II study of Dianhydrogalactitol (VAL-083) In Patients With Recurrent Malignant Glioma," was accepted for poster presentation at the 20th Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology being held November 19 – 22, 2015, in San Antonio, Texas (Press release, DelMar Pharmaceuticals, NOV 9, 2015, View Source [SID:1234508154]).

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The poster presentation will include an update on the Company’s fully enrolled 14-patient expansion cohort from its Phase II clinical study of VAL-083 (dianhydrogalactitol) in refractory glioblastoma multiforme (GBM). Patients enrolled in the GBM trial have failed both front-line therapy with temozolomide and second-line Avastin and, in most cases, one or more salvage therapies.

DelMar recently completed enrollment in the Phase II study and confirmed 40mg/m2 as the maximum tolerated dose (MTD) for advancement into registration-directed Phase II/III clinical trials in GBM.

The Company previously presented data from the Phase I dose-escalation portion of its multicenter Phase I/II clinical study with VAL-083 in patients with recurrent GBM in which dose limiting toxicity was observed at 50mg/m2/day, no drug-related severe adverse events were reported, and myelosuppression was mild at doses <40mg/m2/day.

Additionally, data on a sub-group analysis for patients receiving up to 5 mg/m2 daily x 3 every 21 days (low dose) versus those patients receiving 30mg/m2 or 40mg/m2 (therapeutic dose) of VAL-083 from the clinical trial were also previously presented. The sub-group analysis supports a dose-dependent and clinically meaningful survival benefit in GBM patients whose tumors had progressed following standard treatment with temozolomide, radiotherapy, bevacizumab and a range of salvage therapies.

DelMar’s abstract has been published online in the 2015 abstract supplement to the Society for Neuro-Oncology’s official journal, Neuro-Oncology, at View Source

About VAL-083

VAL-083 is a "first-in-class," small-molecule chemotherapeutic. In more than 40 Phase I and II clinical studies sponsored by the U.S. National Cancer Institute, VAL-083 demonstrated clinical activity against a range of cancers including lung, brain, cervical, ovarian tumors and leukemia both as a single-agent and in combination with other treatments. VAL-083 is approved in China for the treatment of chronic myelogenous leukemia (CML) and lung cancer, and has received orphan drug designation in Europe and the U.S. for the treatment of malignant gliomas.

DelMar has demonstrated that VAL-083’s anti-tumor activity is unaffected by the expression of MGMT, a DNA repair enzyme that is implicated in chemotherapy resistance and poor outcomes in GBM patients following standard front-line treatment with Temodar (temozolomide).

DelMar recently announced the completion of enrollment in a Phase II clinical trial of VAL-083 in refractory GBM. Patients have been enrolled at five clinical centers in the United States: Mayo Clinic (Rochester, MN); UCSF (San Francisco, CA) and three centers associated with the Sarah Cannon Cancer Research Institute (Nashville, TN, Sarasota, FL and Denver, CO).

In the Phase I dose-escalation portion of the study, VAL-083 was well tolerated at doses up to 40mg/m2 using a regimen of daily x 3 every 21 days. Adverse events were typically mild to moderate; no treatment-related serious adverse events reported at doses up to 40 mg/m2. Dose limiting toxicity (DLT) defined by thrombocytopenia (low platelet counts) was observed in two of six (33%) of patients at 50 mg/m2. Generally, DLT-related symptoms resolved rapidly and spontaneously without concomitant treatment, although one patient who presented with hemorrhoids received a platelet transfusion as a precautionary measure.

Sub-group analysis of data from the Phase I dose-escalation portion of the study suggested a dose-dependent and clinically meaningful survival benefit following treatment with VAL-083 in GBM patients whose tumors had progressed following standard treatment with temozolomide, radiotherapy, bevacizumab and a range of salvage therapies.

Patients in a low dose (≤5mg/m2) sub-group had a median survival of approximately five (5) months versus median survival of approximately nine (9) months for patients in the therapeutic dose (30mg/m2 & 40mg/m2) sub-group following initiation of VAL-083 treatment. DelMar reported increased survival at 6, 9 and 12 months following initiation of treatment with VAL-083 in the therapeutic dose sub-group compared to the low dose sub-group.

(Filing, 10-Q, Curis, NOV 9, 2015, View Source [SID:1234508134])

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(Filing, 10-Q, Northwest Biotherapeutics, NOV 9, 2015, View Source [SID:1234508169])

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On November 09, 2015 Advaxis, Inc. (NASDAQ:ADXS), a clinical-stage biotechnology company developing cancer immunotherapies, reported it presented a poster featuring clinical development advances with its Lm Technology at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2015 Annual Meeting in National Harbor, Md (Press release, Advaxis, NOV 9, 2015, View Source [SID:1234508128]). The purpose of this study was to evaluate whether axalimogene filolisbac could be dosed at higher levels than previous studies conducted by Advaxis in patients with persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRmCC).

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While previous clinical studies of axalimogene filolisbac were evaluated at 1 x 109 CFU, data from this Phase 1 dose escalation study showed axalimogene filolisbac may be safely administered with prophylactic antibiotics up to 1 x 1010 CFU, a tenfold increase. Higher doses of axalimogene filolisbac have been shown pre-clinically to correlate with increased antigen presentation and greater targeted anti-tumor activity.

Clinical data from the ongoing Phase 1/2 clinical trial reported the first evidence for the safety and tolerability of axalimogene filolisbac at higher doses in patients with PRmCC. In the study, a total of 27 cycles of therapy were delivered at the 5 x 109 CFU dose level and to date, 5 cycles at the high dose of 1 x 1010 CFU, which will now constitute the randomized Phase 2 dose (RP2D). The adverse events observed at the high dose are consistent with previous experience.

"I’m extremely excited about this study because we have evaluated doses of axalimogene filolisbac at 5 and 10 times the level currently administered in the clinical trial program to date, with the goal of evaluating whether the increased dose and protein expression may lead to greater clinical benefit," said principal investigator Sharad Ghamande, M.D., Director of Gynecology Oncology at GRU Cancer Center, Georgia Regents University in Augusta, Ga. "Importantly, even at higher doses, the adverse event profile continues to be predominantly grade 1 grade 2, transient events, self-resolving within hours or resolving promptly with the introduction of anti-inflammatory medications."

The RP2D will now be explored further in an expansion cohort in subjects with PRmCC.

About Cervical Cancer

Cervical cancer is the fourth most common cancer and the most common cause of mortality in women worldwide. In the United States, nearly 13,000 new cases are diagnosed and approximately 4,100 deaths are reported because of cervical cancer. According to the WHO/ICO Information Centre on HPV and Cervical Cancer, about 3.9 percent of women in the U.S. are estimated to harbor high-risk cervical HPV infection at a given time, and 71.7 percent of invasive cervical cancers are attributed to high-risk HPV strains.

About Axalimogene Filolisbac

Axalimogene filolisbac (ADXS-HPV) is Advaxis’s lead Lm Technology immunotherapy candidate for the treatment of HPV-associated cancers and is in clinical trials for three potential indications: invasive cervical cancer, head and neck cancer, and anal cancer. In a completed randomized Phase 2 study in recurrent/refractory cervical cancer, axalimogene filolisbac showed apparent prolonged survival, objective tumor responses, and a manageable safety profile alone or in combination with chemotherapy, supporting further development of the company’s Lm Technology.