On November 21, 2016 ImmunoCellular Therapeutics, Ltd. ("ImmunoCellular") (NYSE MKT:IMUC) reported the presentation of updated immune monitoring data from the phase 2 trial of ICT-107 in patients with newly diagnosed glioblastoma (Press release, ImmunoCellular Therapeutics, NOV 21, 2016, View Source [SID1234516718]). Also presented were updated long-term survival data from the phase 1 trial of ICT-107. ICT-107 is a dendritic cell-based immunotherapy targeting multiple tumor-associated antigens on glioblastoma stem cells. ICT-107 is currently being tested in a phase 3 registration trial in patients with newly diagnosed glioblastoma. The updated phase 1 and phase 2 data were presented in two oral sessions on Friday, November 18th, at the 21st Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology, held in Scottsdale, AZ.

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The ICT-107 phase 2 trial was a randomized, double-blind, placebo-controlled phase 2 study of the safety and efficacy of ICT-107 in patients with newly diagnosed glioblastoma following resection and chemoradiation. ICT-107 is an intradermally administered autologous immunotherapy consisting of the patient’s own dendritic cells pulsed with six synthetic tumor-associated antigens: AIM-2, MAGE-1, TRP-2, gp100, HER-2, IL-13Rα2. The placebo control consisted of the patient’s unpulsed dendritic cells. The data from the phase 2 trial indicated a survival advantage in the ICT-107 treated group compared to the control group. The data also showed an association between immune response and survival, especially in HLA-A2 positive (HLA-A2+) patients, which is the target patient population for the ongoing phase 3 registration trial.

The updated immune response data from the phase 2 trial showed that treatment with ICT-107 resulted in the development of a measurable anti-tumor T cell response in some patients, which was associated with survival. Patients that developed the anti-tumor T cell response which was measurable by both ELISpot (to detect viable T cells capable of binding to a target antigen) and multimer testing (to detect T cell binding with higher sensitivity than ELISpot) had improved survival. The data demonstrated that immuno-monitoring can provide an early indication of patients responding to immunotherapy. In the current ongoing phase 3 registration trial of ICT-107, ImmunoCellular plans to perform immuno-monitoring to support the trial.

The data were presented at SNO by Steven J. Swanson, PhD, Senior Vice President, Research, ImmunoCellular Therapeutics, in a presentation titled, "Categorizing immune responders with fusion metrics and simulation for association to survival and progression-free survival with immune response in HLA-A2+ patients with GBM from a phase 2 trial of dendritic cell (DC) immunotherapy (ICT-107)."

Dr. Swanson commented: "ICT-107 is designed to deliver therapeutic benefit by stimulating the patient’s immune system to attack tumor tissue. A first indicator that the immunotherapeutic is active is the production of tumor-specific T cells by the patient. In our SNO presentation, we described our ability to more clearly interpret the immune-monitoring data from the phase 2 trial. The ability to accurately identify negative and positive responses enabled us to better understand which of the patients in our trial generated T cells capable of attacking the tumor. We determined that patients with a T cell response measureable in both the ELIspot assay and through multimer analysis achieved longer survival as compared with patients who did not show a positive response. These data should enable us to better interpret the results of our ongoing phase 3 trial."

Andrew Gengos, ImmunoCellular Chief Executive Officer, said: "The phase 2 trial immune monitoring results indicate that patients who mount a T cell response appear to have improved survival over those without a detectable response. In designing the phase 3 trial, we have made important changes in the protocol to potentially enhance the immune response in ICT-107 treated patients with the goal of optimizing the potential survival outcomes in the trial."

Data from the phase 1 trial of ICT-107 were presented by Surasak Phuphanich, MD, Department of Neurology, Cedars-Sinai in Los Angeles, in a presentation titled "Ten-year follow up with long term remission in patients with newly diagnosed glioblastoma (GBM) treated with ICT-107 vaccine (phase 1)." The phase 1 open-label, single institution trial, which was completed in 2010, included 16 evaluable patients with newly diagnosed glioblastoma. Results of the study were initially published in 2012 (Cancer Immunol Immunother).

Updated survival data presented by Dr. Phuphanich at the 2016 SNO meeting showed that 19% of patients had long-term remission of greater than 8 years, with the longest remission being 9.6 years. Also, 38% of patients demonstrated long-term survival of greater than 8 years, with the longest survivor greater than 10.2 years. Immune response data showed a correlation between survival and cancer-stem-associated expression, and a trend toward greater CD8 T cell cytokine responses in long-term survivors.

ICT-107 Phase 3 Registration Trial Underway

The ongoing phase 3 registrational trial of ICT-107 is designed as a randomized, double-blind, placebo-controlled study of HLA-A2+ subjects, which is being conducted at about 120 sites in the US, Canada and the EU, with plans to randomize at least 500 patients with newly diagnosed glioblastoma. The primary endpoint in the trial is overall survival. Secondary endpoints include progression-free survival and safety, as well as overall survival in the two pre-specified MGMT subgroups.

For patients, families and physicians seeking additional information about the ICT-107 phase 3 trial, please consult www.clinicaltrials.gov.

About ImmunoCellular Therapeutics, Ltd.

On November 18, 2016 Argos Therapeutics Inc. (Nasdaq:ARGS) ("Argos"), an immuno-oncology company focused on the development and commercialization of individualized immunotherapies based on the Arcelis technology platform, and its partner Cellthera Pharm ("Cellthera"), a subsidiary of Pharmstandard focused on personalized therapeutics, reported the presentation of data on a murine ("mouse") model developed by Cellthera to determine functional activity of a therapy modeled after Argos’ AGS-003 individualized immunotherapy (Press release, Argos Therapeutics, NOV 18, 2016, View Source [SID1234516678]). The data were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 31st Annual Meeting, which was held November 11-13 in National Harbor, Maryland.

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The data presented demonstrated the favorable effects of the AGS-003-like therapy as a single agent and in combination with sunitinib and a PD-1 checkpoint inhibitor in a murine model of renal cell carcinoma (RCC). "Our model provides some exciting survival data using an AGS-003-like therapy in a murine kidney cancer model that has proven useful in exploring combinations with other agents in a relevant preclinical setting," said Dr. Alexander Shuster, chairman of Cellthera. In this experiment the agents were administered alone or together 7 days prior to the inoculation of tumor cells and then each group was followed for tumor reduction and survival. Dr. Shuster continued, "The prophylactic mouse data show the superiority of the AGS-003-like therapy as a single agent versus control in both survival and enhanced control of tumor growth. Furthermore, the AGS-003-like therapy when combined with sunitinib or a PD-1 checkpoint inhibitor outperformed each agent alone, and the combination of all three therapies demonstrated the strongest survival advantage."

Argos is currently evaluating AGS-003 in combination with standard of care agents in the pivotal ADAPT Phase 3 clinical trial for the treatment of metastatic renal cell carcinoma (mRCC). Enrollment in this 462-patient study was initiated in February 2013 and completed in July 2015. The Independent Data Monitoring Committee (IDMC) for this study most recently recommended continuation of the study following a meeting in June 2016, with the next IDMC meeting planned for February 2017. In addition, AGS-003 is being studied in Phase 2 investigator-initiated clinical trials as neoadjuvant therapy for RCC and for the treatment of non-small cell lung cancer (NSCLC).

"These mouse data support the expectation of enhanced clinical benefit for the combination of AGS-003 with checkpoint inhibitors and, importantly, also show that amplified total tumor RNA is essential to the anti-tumor activity of Arcelis-derived dendritic cells," noted Dr. Charles Nicolette, chief scientific officer and vice president of research and development at Argos. "Additionally, the observation in mice that the AGS-003-like therapy and sunitinib are each active separately and lead to improved control of tumor growth when combined bodes well for our ongoing Phase 3 ADAPT trial in advanced renal cell carcinoma where AGS-003 is initially being combined with sunitinib."

A copy of this and other Argos-related publications can be found at:
View Source

About the Arcelis Technology Platform
Arcelis is a precision immunotherapy technology that captures both mutated and variant antigens that are specific to each patient’s individual disease. It is designed to overcome immunosuppression by producing a specifically targeted, durable memory T-cell response without adjuvants that may be associated with toxicity. The technology is potentially applicable to the treatment of a wide range of different cancers and infectious diseases and is designed to overcome many of the manufacturing and commercialization challenges that have impeded other personalized immunotherapies. The Arcelis process uses only a small disease sample or biopsy as the source of disease-specific antigens and the patient’s own dendritic cells, which are optimized from cells collected by a leukapheresis procedure. The proprietary process uses RNA isolated from the patient’s disease sample to program dendritic cells to target disease-specific antigens. These activated, antigen-loaded dendritic cells are then formulated with the patient’s plasma and administered via intradermal injection as an individualized immunotherapy.

On November 17, 2016 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in Hematology and Oncology, reported that scientists from MD Anderson Cancer Center will be presenting data from a preclinical study evaluating poziotinib in lung cancer at the 17th International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer taking place in Vienna, Austria, December 4-7, 2016 (Press release, Spectrum Pharmaceuticals, NOV 17, 2016, View Source [SID1234516662]).

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"Poziotinib has shown promising efficacy in preclinical models of non-small cell lung cancer (NSCLC) with exon 20 insertion mutations," said John Heymach, MD, PhD, Chairman, Professor, and David Bruton Junior Chair in Cancer Research, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center. "Tumors with these mutations have generally not been responsive to approved EGFR inhibitors, and there is an unmet need for better therapies for these patients. Computational modeling suggests that poziotinib may overcome steric hindrance of the drug binding pocket induced by the exon 20 insertion mutations. Based on these results, we are in the process of initiating a Phase 2 study in lung cancer that we plan to start in the near future."

"Poziotinib has already shown promising data in breast cancer, and we are excited that it may now have application in lung cancer as well," said Rajesh C. Shrotriya, MD, Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. "Lung cancer is the leading cause of cancer deaths in the world. Due to the mutations in the genes, lung cancer often becomes unresponsive to treatments. Patients who have exon 20 insertion mutations have few options, if any. We look forward to working closely with MD Anderson Cancer Center to continue development of this drug in this area of unmet medical need."

17th IASLC World Conference on Lung Cancer

Abstract Title:
Poziotinib overcomes de novo resistance of EGFR exon 20 insertion mutations in NSCLC
Oral Presentation Schedule:
December 7, 2016 Session "Novel Strategies in Targeted Therapies"
Abstract Link:
View Source

About Poziotinib

Poziotinib is a novel, oral pan-HER inhibitor that irreversibly blocks signaling through the Epidermal Growth Factor Receptor (EGFR, HER) Family of tyrosine-kinase receptors, including HER1 (erbB1; EGFR), HER2 (erbB2), and HER4 (erbB4), and importantly, also HER receptor mutations; this, in turn, leads to the inhibition of the proliferation of tumor cells that overexpress these receptors. Mutations or overexpression/amplification of EGFR family receptors have been associated with a number of different cancers, including non-small cell lung cancer (NSCLC), breast cancer, and gastric cancer.

On November 17, 2016 Triphase Accelerator Corporation, a private drug development company dedicated to advancing novel compounds through Phase 2 proof-of-concept, reported that Celgene Corporation, through an affiliate, has acquired the company’s assets related to its proteasome inhibitor, marizomib (MRZ), which is in development for glioblastoma and relapsed and/or refractory multiple myeloma (Press release, Celgene, NOV 17, 2016, View Source [SID1234527214]).

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Under the terms of the agreement, Celgene will make an upfront payment plus additional regulatory, approval and sales milestone payments. Specific financial terms were not disclosed. "This acquisition validates the potential of marizomib based on early clinical results. Our vision is to become a leading early stage oncology drug development company, and this first opt-in by Celgene brings us a step closer to achieving that goal," said Mohit Trikha, Ph.D., chief scientific officer, Triphase Accelerator Corporation. "Just as importantly, this transaction affords us the opportunity to accelerate our efforts on advancing other assets in our pipeline."

"Consistent with our deep commitment and passion for the patients, glioblastoma is an area of significant unmet medical need, and Celgene is committed to helping these patients. We are pleased with Triphase Accelerator’s rapid and high quality work to date, and we value the exceptional collaboration we have with them to advance marizomib," said Celgene’s President of Hematology Oncology, Michael Pehl.

Going forward Celgene has full responsibility for the development of marizomib and will pay Triphase to complete the ongoing clinical studies with marizomib, including a Phase 1 study in relapsed refractory multiple myeloma, a Phase 2 study in recurrent glioma and a Phase 1 study in newly diagnosed glioma.

About Marizomib
Marizomib is a novel, brain-penetrant proteasome inhibitor, which inhibits all three proteasome subunits.

Triphase Accelerator is developing marizomib in both intravenous (IV) and oral formulations as a proteasome inhibitor for hematologic malignancies and solid tumors. The IV formulation has been evaluated in more than 300 patients in multiple clinical studies in patients with solid and hematologic malignancies, either as a single agent or in combination with dexamethasone, a histone deacetylase inhibitor, or an immunomodulatory drug.

The company is currently evaluating marizomib in a proof-of-concept clinical study in combination with bevacizumab (Avastin) in patients with Grade IV malignant glioma (glioblastoma), and has received Orphan Drug designation for marizomib in glioblastoma in the United States from the FDA. In addition, Triphase Accelerator is currently developing marizomib in combination with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma, and has received Orphan Drug designation for marizomib in multiple myeloma in the United States and the European Union. Triphase Accelerator is also evaluating an oral formulation in preclinical studies.

Marizomib has not been approved for any use in any country.

On November 15, 2016 Cellectar Biosciences, Inc. (Nasdaq: CLRB) (the "company"), an oncology-focused, clinical stage biotechnology company, reported it has selected INC Research (Nasdaq: INCR), a leading, global Phase I to IV contract research organization, to oversee its NCI-supported Phase II clinical trial of CLR 131 in patients with multiple myeloma and select hematologic malignancies (Filing, 8-K, Cellectar Biosciences, NOV 17, 2016, View Source [SID1234516654]). The company anticipates that its $2M NCI grant will cover approximately 50 percent of the study’s cost, and the terms of the grant allow Cellectar to pursue an additional $3M for a pivotal Phase III trial of the company’s lead radiotherapeutic compound.

Cellectar plans to leverage the results of its 80-patient, Phase II study to optimally design its pivotal trial of CLR 131 in multiple myeloma and other hematologic malignancies. The multi-armed study will include relapse/refractory patients with multiple myeloma (MM), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and potentially diffuse large B-cell lymphoma (DLBCL), who have been treated with standard therapy for their underlying malignancies. The company recently accelerated its guidance and announced plans to initiate the trial during the first quarter of 2017.

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"INC Research has outstanding experience in cancer clinical research and a strong reputation within the hematology community. With strong investigator relationships, proven operational expertise and a commitment to high-quality data, they are the ideal partner for this important trial," said Jim Caruso, president and CEO of Cellectar. "Given the accelerated initiation of our Phase II study to the first quarter of 2017 and that we will utilize as many as 15 participating sites, we can confidently plan on providing initial efficacy data in the second half of 2017."

About CLR 131
CLR 131 is an investigational compound under development for a range of hematologic malignancies. It is currently being evaluated in a Phase I clinical trial in patients with relapsed or refractory multiple myeloma. The company plans to initiate a Phase II clinical study to assess efficacy in a range of B-cell malignancies in the first quarter of 2017. Based upon preclinical and interim Phase I study data, treatment with CLR 131 provides a novel approach to treating hematological diseases and may provide patients with therapeutic benefits, including overall response rate (ORR), an improvement in progression-free survival (PFS) and overall quality of life. CLR 131 utilizes the company’s patented PDC tumor targeting delivery platform to deliver a cytotoxic radioisotope, iodine-131 directly to tumor cells. The FDA has granted Cellectar an orphan drug designation for CLR 131 in the treatment of multiple myeloma.

About Phospholipid Drug Conjugates (PDCs)
Cellectar’s product candidates are built upon its patented cancer cell-targeting delivery and retention platform of optimized phospholipid ether-drug conjugates (PDCs). The company deliberately designed its phospholipid ether (PLE) carrier platform to be coupled with a variety of payloads to facilitate both therapeutic and diagnostic applications. The basis for selective tumor targeting of our PDC compounds lies in the differences between the plasma membranes of cancer cells compared to those of normal cells. Cancer cell membranes are highly enriched in lipid rafts, which are glycolipoprotein microdomains of the plasma membrane of cells that contain high concentrations of cholesterol and sphingolipids, and serve to organize cell surface and intracellular signaling molecules. PDCs have been tested in over 70 different xenograft models of cancer.

About Relapsed or Refractory Multiple Myeloma
Multiple myeloma is the second most common blood or hematologic cancer with approximately 30,000 new cases in the United States every year. It affects a specific type of blood cells known as plasma cells. Plasma cells are white blood cells that produce antibodies to help fight infections. While treatable for a time, multiple myeloma is incurable and almost all patients will relapse or the cancer will become resistant/refractory to current therapies.