On November 21, 2016 Kite Pharma, Inc. (Nasdaq:KITE) reported that data from the interim analysis of the pivotal ZUMA-1 trial of KTE-C19 in patients with chemorefractory aggressive non-Hodgkin lymphoma (NHL) have been accepted as an oral late-breaking presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) 58th Annual Meeting in San Diego, CA, on December 6, 2016 (Press release, Kite Pharma, NOV 21, 2016, View Source [SID1234516710]). The abstract was one of only six accepted in this category and will be included in the December 1 online issue of Blood. Schedule your 30 min Free 1stOncology Demo! "Outcomes for patients with aggressive NHL depend on whether their disease is sensitive to chemotherapy. The ZUMA-1 study was designed to support registration of KTE-C19 by enrolling a well-defined chemorefractory patient population," said Jeff Wiezorek, M.D., Senior Vice President of Clinical Development of Kite. "We are pleased with the outcome of the study to date and thank the patients and investigators for their participation in the first positive pivotal study in CAR-T therapy."
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
The abstract, titled "KTE-C19 (anti-CD19 CAR T Cells) Induces Complete Remissions in Patients with Refractory Diffuse Large B-Cell Lymphoma (DLBCL): Results from the Pivotal Phase 2 ZUMA-1," will be presented by Sattva S. Neelapu, M.D., Associate Professor at the University of Texas MD Anderson Cancer Center, Houston, TX.
Session Information
Session Name: Late-Breaking Abstracts Session
Session Date: Tuesday, December 6, 2016
Session Time: 7:30 AM – 9:00 AM PT
Presentation Time: 8:45 AM PT
Room: San Diego Convention Center, Hall AB
This oral presentation will feature interim results from the ZUMA-1 Phase 2 trial. In September 2016, Kite announced ZUMA-1 positive interim topline results (objective response rate 79 percent; complete remission rate 52 percent) from 62 patients with 3 months of follow-up in both Cohort 1 and Cohort 2. Cohort 1 included patients with DLBCL, and Cohort 2 enrolled patients with transformed follicular lymphoma (TFL) and primary mediastinal B-cell lymphoma (PMBCL). Details of data available at the time of interim analysis, including 93 patients who had the opportunity to be followed for one month, will be presented in the late-breaker presentation on December 6, 2016. Cohort 2 data will be covered in a separate oral presentation on December 5, 2016: Abstract #998, A Phase 2 Multicenter Trial of KTE-C19 (anti-CD19 CAR T Cells) in Patients with Chemorefractory Primary Mediastinal B-Cell Lymphoma (PMBCL) and Transformed Follicular Lymphoma (TFL): Interim Results From ZUMA-1, View Source
About KTE-C19
Kite Pharma’s lead product candidate, KTE-C19, is an investigational therapy in which a patient’s T cells are engineered to express a CAR to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias, and redirect the T cells to kill cancer cells. KTE-C19 has been granted Breakthrough Therapy Designation status for diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL) by the U.S. Food and Drug Administration (FDA) and Priority Medicines (PRIME) regulatory support for DLBCL in the EU.
DelMar Pharmaceuticals Delivers an Address and Presents an Overview of Upcoming GBM Trials with VAL-083 at the CNS Anticancer Drug Discovery Development Conference and Society for NeuroOncology Annual Meeting
On November 21, 2016 DelMar Pharmaceuticals, Inc. (NASDAQ: DMPI) ("DelMar" and the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, reported the Company’s presentations at the CNS Anticancer Drug Discovery and Development Conference and Society for NeuroOncology Annual meeting, which was held November 16-20, 2016 in Scottsdale, Arizona (Press release, DelMar Pharmaceuticals, NOV 21, 2016, http://ir.delmarpharma.com/news/detail/838/delmar-pharmaceuticals-delivers-an-address-and-presents-an-overview-of-upcoming-gbm-trials-with-val-083-at-the-cns-anticancer-drug-discovery-development-conference-and-society-for-neurooncology-annual-meeting [SID1234516708]). Schedule your 30 min Free 1stOncology Demo! During the conference, DelMar’s chairman and CEO, Jeffrey Bacha, delivered an oral address during CNS Anticancer Drug Discovery and Development sessions. Mr. Bacha described DelMar’s research and recent clinical trial results and how these data position VAL-083 as a potential solution for newly diagnosed GBM patients whose cancer exhibits features, such as a high expression of MGMT, implicated in resistance to currently approved chemotherapy.
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"It was an honor to be invited to share and discuss our research with leaders in the global neuro-oncology community," stated Mr. Bacha. "Overcoming the unique challenges in treating brain tumors requires cooperation among experts across a range of medical and scientific disciplines. We look forward to continuing to advance VAL-083 as a potential new chemotherapy in collaboration with leading cancer centers and researchers."
DelMar also provided an overview of three upcoming clinical trials with VAL-083 for the treatment of chemo-resistant GBM. A copy of the company’s poster presentation entitled ‘Clinical Trials of VAL-083 in Patients with Chemo-Resistant Glioblastoma’ can be viewed at View Source The planned trials include:
1. A pivotal, randomized multi-center Phase 3 study measuring survival outcomes compared to a "physicians’ choice" control for the treatment of bevacizumab-failed GBM. A summary of the proposed clinical trial design includes:
Approximately 180 patients with histologically confirmed recurrent GBM who have failed both standard chemo-radiation and bevacizumab will be randomized in a 2:1 fashion to receive either VAL-083 or a commonly used salvage chemotherapy;
The proposed study is projected to be enrolled at approximately 25 centers;
The proposed primary endpoint is overall survival (OS);
The proposed statistical design between the two arms of the study is 90% power, and is proposed to include an interim analysis at 50% events for futility with O’Brien-Fleming superiority boundary and non-binding, gamma (-5) futility boundary; and
The estimated length of the proposed study is less than two years from initiation.
The proposed trial design is subject to feedback from the FDA and other regulatory authorities. DelMar plans to submit the protocol to the FDA in coming weeks.
2. An open label, single-arm, biomarker-driven, Phase 2 study of VAL-083 in patients with MGMT-unmethylated, bevacizumab-naïve recurrent GBM (clinicaltrials.gov identifier: NCT02717962)
This single arm, biomarker-driven study will enroll 48 patients to determine if treatment of MGMT-unmethylated recurrent glioblastoma with VAL-083 improves overall survival (OS), compared to historical reference control;
The lomustine arm of the recently published EORTC26101 trial will serve as the reference control; and
The study is initially being enrolled at the University of Texas MD Anderson Cancer Center as a single center trial, but may be expanded to include additional centers.
This trial is being conducted in collaboration with the University of Texas MD Anderson Cancer Center ("MDACC"). The MDACC Institutional Review Board (IRB) has approved the protocol for this Phase II Study, and DelMar has completed a formal site initiation visit. DelMar and MDACC anticipate commencing enrollment and initiating patient treatment in the coming weeks.
3. An open label, single-arm, biomarker-driven, Phase 2 study of VAL-083 and radiation therapy patients in newly diagnosed MGMT-unmethylated GBM
This single-arm trial will enroll up to 30 newly diagnosed (temozolomide-naïve) GBM patients to examine whether VAL-083 is active in patients with newly diagnosed GBM with MGMT-unmethylated compared to historical control;
If successful, data from the trial will serve as a lead-in to a global randomized Phase II/III clinical trial of VAL-083 in newly diagnosed GBM patients with MGMT-unmethylated;
Progression free survival (PFS) will serve as the primary endpoint to assess VAL-083 treatment activity;
The study will also confirm the safety and tolerability of VAL-083 in combination with a standard-of-care radiation regimen; and
The study will initially be enrolled at the Sun-Yat Sen University (Guangzhou, China) as a single center trial, but may be expanded to include additional centers.
This trial is being conducted in collaboration with Guangxi Wuzhou Pharmaceutical (Group) Co. Under the terms of the company’s collaboration agreement Guangxi Wuzhou Pharmaceuticals is providing drug product and funding for the trial. The Sun-Yat Sen University Clinical Review Committee has approved the protocol and DelMar is completing the final remaining regulatory steps required for initiation of the trial and expects to begin enrollment in early 2017.
In a separate poster presentation, DelMar provided additional non-clinical data regarding VAL-083’s unique anti-cancer mechanism and potential combination therapies. DelMar’s poster presentation, entitled ‘Molecular Mechanisms of Dianhydrogalactitol (VAL-083) in Overcoming GBM Chemo-resistance’ can be viewed on the company’s website at: View Source
In summary, DelMar’s data indicates that:
The mechanism of action of VAL-083 is distinct from other alkylating agents used in the treatment of CNS tumors;
VAL-083 induces irreparable DNA double strand breaks, irreversible S/G2-phase arrest and activation of the homologous recombination DNA repair pathway;
VAL-083’s cytotoxic activity is MGMT-independent and able to overcome TMZ-resistance in GBM cancer stem cells and non-stem cells in vitro;
VAL-083 potentiates radiation in GBM cancer stem cells in vitro;
VAL-083’s activity appears independent of p53; and
VAL-083 displays synergy with a number of agents used in the treatment of GBM and other CNS tumors, including temozolomide, topoisomerase inhibitors, and platinum-based chemotherapy.
"These data are particularly valuable because they demonstrate the potential to combine VAL-083 with topoisomerase inhibitors, which are regularly used in the treatment of recurrent GBM," added Mr. Bacha. "Topoisomerase inhibitors such as irinotecan and etoposide have a relatively narrow therapeutic window and require cells to be in the ‘S-phase’ of the cell cycle for activity. Because VAL-083 causes cell-cycle arrest in the S-phase these data suggest an opportunity to combine VAL-083 with a lower and better tolerated dose of a topoisomerase inhibitor while maintaining or improving efficacy."
About Glioblastoma Multiforme (GBM)
Glioblastoma multiforme (GBM) is the most common and most malignant form of brain cancer. Approximately 15,000 people are diagnosed with GBM each year in the U.S., with similar incidence in Europe. Standard of care is surgery, followed by either radiation therapy, or radiation therapy combined with temozolomide. Approximately 60 percent of GBM patients treated with temozolomide experience tumor progression within one year. More than half of glioblastoma patients will fail the currently approved therapies and face a very poor prognosis.
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.
DelMar’s research has demonstrated that VAL-083 is active against GBM cell lines that are resistant to standard-of-care chemotherapy due to features such as high expression of MGMT, in vitro.
DelMar presented data from its Phase I/II clinical trial in refractory GBM at the 2016 American Association of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual meeting demonstrating that the median survival of 22 patients receiving an assumed therapeutic dose of VAL-083 (≥20mg/m2) was 8.35 months following Avastin (bevacizumab) failure compared to published literature where survival of approximately two to five months has been reported.
VAL-083 has received an orphan drug designation in Europe for the treatment of malignant gliomas and the U.S. FDA Office of Orphan Products has granted an orphan designation to VAL-083 for the treatment of glioma, medulloblastoma and ovarian cancer.
DelMar believes that data from its upcoming clinical trials, if successful, will form the basis of a new paradigm in the treatment for all GBM patients who fail, or whose tumors exhibit features that make them unlikely to respond to currently available chemotherapy.
Further details can be found at View Source
Partial Clinical Hold Lifted and Enrollment Resumes for Aduro Biotech LADD Clinical Trials
On November 21, 2016 Aduro Biotech, Inc. (Nasdaq:ADRO), a biopharmaceutical company with three distinct immunotherapy technologies, reported that the U.S. Food and Drug Administration (FDA) has lifted the partial clinical hold placed on its clinical trials evaluating the LADD (live, attenuated double-deleted) immunotherapy platform, enabling patient enrollment to resume in all Aduro-sponsored clinical studies (Press release, Aduro BioTech, NOV 21, 2016, View Source [SID1234516707]). Schedule your 30 min Free 1stOncology Demo! "We are pleased to come to a rapid agreement with the FDA to resume new patient enrollment in our LADD clinical studies," said Stephen T. Isaacs, chairman, president and CEO of Aduro Biotech. "With slight protocol modifications implemented, we remain on track to initiate a Phase 2 clinical study using our LADD-based therapy CRS-207 in combination with an anti-PD-1 compound for patients with mesothelioma in the first half of 2017. Additionally, we continue to make significant progress with our STING Pathway Activator and B-select Antibody programs and with our three diverse immunotherapy platforms, we believe we are uniquely positioned to bring innovative therapies to patients with late-stage cancers."
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
In agreement with the FDA, Aduro’s LADD-based clinical trial protocols have been modified to include extended patient surveillance, to exclude patients with certain prosthetic devices that are not easily removed, and to add guidance to administer prophylactic antibiotics following LADD-based treatment for patients who may receive immune-suppressive treatments.
Cellthera Presents Preclinical Data at SITC Using Argos’ Individualized Immunotherapy
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.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
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.
Peptide-based vaccination against VEGF results in efficient antitumor activity
On November 18, 2016 Immunovo reported on the successful development of a peptide-based vaccine enabling a successful active anti-tumor immunization therapy targeting the growth hormone Vascular Endothelial Growth Factor (VEGF) (Press release, Immunovo, NOV 18, 2016, View Source [SID1234516684]). An academic research team, in collaboration with Immunovo, has established that treatment with vaccine caused suppression of tumor growth in mice. These encouraging preclinical results were published last week in the leading international journal "Proceedings of the National Academy of Sciences of the USA" (PNAS). An exploratory Phase I/II studie in patients is now well underway at VU Medical Center (Amsterdam, The Netherlands). Schedule your 30 min Free 1stOncology Demo! The vascular endothelial growth factor (VEGF) is a pivotal growth factor for angiogenesis (blood vessel formation) in tumor tissue. Therefore, it has been frequently investigated as a target in anticancer therapy. Its inhibition by the monoclonal anti-VEGF antibody bevacizumab (Avastin) has already demonstrated improved survival in patients with several types of cancer.
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
There are, however, limitations to the effectiveness of this passive immunotherapy strategy since it does not stimulate a patient’s immune system to actively respond to a disease in the way a vaccine does. The starting point of the research now reported in PNAS is that a VEGF vaccination has the potential to outperform the current clinical anti-VEGF treatment strategies.
Vaccination will not only provide durable VEGF suppression, it is also expected that the induced antibodies will have superior VEGF-neutralizing ability in comparison to bevacizumab. Furthermore, vaccination requires only a few intramuscular injections and reduces the number of hospital visits in comparison to treatment with bevacizumab.
However, vaccination with intact VEGF has major drawbacks such as unwanted biological activity and weak immunogenicity. The strategy pursued in the current research therefore is to use a VEGF mimicking peptide as a vaccine. The major challenge here was to identify the minimal peptide able to generate antisera with potent VEGF-neutralizing capacity and tumor-reducing capabilities.
A total of 33 peptide mimics of VEGF with varying levels of structural complexity (linear, conformational, and discontinuous) were designed, synthesized, and tested for the ability to generate potent antisera. It was established that induction of neutralizing antibodies with tumor-growth-inhibiting power was only successful for a 3D-structured 79-mer peptide with a fully intact cysteine-knot fold (covering the complete discontinuous binding site of bevacizumab).
Eradication of tumor growth using this peptide was demonstrated in two different tumor models (mice). It thus became clear that enforcing a native-like, secondary structure in the peptide is the key to success for inducing neutralizing anti-VEGF antibodies with tumor-inhibiting power.
Joost van Bree, CEO of Immunovo explains: "At Immunovo, we think that clinical benefit could be enhanced by inducing a humoral immune response against VEGF through active immunization with VEGF-based peptides. In this study we demonstrated the successful development of a unique synthetic vaccine with potent in vitro and in vivo VEGF-neutralizing activities, as shown in passive and active immunization tumor models. We strongly believe that this strategy has the exciting potential to outperform the current clinical anti-VEGF treatment strategies"
The research team included Professor Peter Timmerman of Pepscan Systems BV and the University of Amsterdam’s Van’t Hoff Institute for Molecular Sciences (HIMS) and Madelon Wentink and Professor Arjan Griffioen, both of VU Medical Center Amsterdam.