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Advaxis to Present at Third CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival

On August 2, 2017 Advaxis, Inc. (NASDAQ:ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, reported three abstracts were selected for presentation at the third annual CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper): Translating Science into Survival (Press release, Advaxis, AUG 2, 2017, View Source [SID1234519986]). The prestigious program brings together leading stakeholders in the field to teach, learn and disseminate the latest cutting-edge information and research in cancer immunology and immunotherapy.

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Two poster presentations will feature preliminary immune correlative data from the ADXS-PSA monotherapy treatment arm of Advaxis’ Phase 1/2 study in combination with KEYTRUDA (pembrolizumab) in metastatic castration-resistant prostate cancer (mCRPC) patients. The third presentation will feature preclinical data with the company’s HPV-targeted immunotherapy, axalimogene filolisbac.

The poster presentation, "Gene expression profiles associated with stable disease in metastatic castration-resistant prostate cancer patients treated with ADXS-PSA immunotherapy," will feature preliminary data identifying potential pharmacodynamic biomarkers of clinical response in mCRPC patients treated with ADXS-PSA monotherapy.

The second poster presentation, "Persistence of expanded TCRβ clonotypes is associated with clinical activity of ADXS-PSA immunotherapy in metastatic castration-resistant prostate cancer," will focus on the stability of expanded T cell clones in mCRPC patients following treatment with ADXS-PSA monotherapy. The preliminary immune correlative data will be presented by Sandy Hayes, Ph.D., Senior Director of Research and Biomarker Lead at Advaxis.

The third poster presentation, "Identification of an intratumoral immune gene signature associated with tumor regression in an axalimogene filolisbac-treated murine HPV+ tumor model," will include preclinical data regarding molecular biomarkers associated with tumor regression in a murine HPV+ tumor model. It will be presented by Rachelle Kosoff, Ph.D., Senior Scientist in Research at Advaxis.

"Our findings provide important insights into identifying those patients who are benefiting from these treatments," said Dr. Hayes. "We’re pleased to share our findings with the rest of the community at the International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) as we continue our work to bring new treatment options to patients."

The third annual International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) takes place in the city of Mainz near Frankfurt, Germany from Sept. 6 – 9, 2017, and is jointly sponsored by the Cancer Research Institute (CRI), the Association for Cancer Immunotherapy (CIMT) (Free CIMT Whitepaper), the European Academy of Tumor Immunology (EATI) and the American Association for Cancer Research (AACR) (Free AACR Whitepaper). Presentations will cover all areas of inquiry in cancer immunology and immunotherapy, including: neoantigens and vaccines, novel mechanisms of immunosuppression and immune evasion, biomarkers, new checkpoint immunotherapies and the tumor microenvironment.

To learn more about Advaxis and its immunotherapy clinical programs, visit www.advaxis.com/clinical-trials.

Helsinn Group and MEI Pharma Announce First Patient Dosed in Pivotal Phase 3 Study of Pracinostat and Azacitidine in Acute Myeloid Leukemia

On August 2, 2017 Helsinn, a Swiss pharmaceutical group focused on building quality cancer care products, and MEI Pharma, Inc. (Nasdaq: MEIP), an oncology company focused on the clinical development of novel therapies for cancer, reported that the first patient has been dosed in the pivotal Phase 3 study of the investigational agent pracinostat in combination with azacitidine in adults with newly diagnosed acute myeloid leukemia (AML) who are unfit to receive intensive induction chemotherapy (Press release, MEI Pharma, AUG 2, 2017, View Source [SID1234519985]).

The randomized, double-blind, placebo-controlled study will enroll approximately 500 eligible patients worldwide. Patients will be randomized 1:1 to receive pracinostat or placebo with azacitidine as background therapy. The primary endpoint of the study is overall survival. Secondary endpoints include, among others, morphologic complete remission (CR) rate, event free survival (EFS) and duration of CR.

Riccardo Braglia, Helsinn Group Vice Chairman and CEO, said: "Helsinn was delighted to be able to announce our strategic partnership with MEI Pharma last year, leveraging on the potential of pracinostat, which was demonstrated in the Phase 2 study. We are very pleased that pracinostat is moving into Phase 3, showing the continued momentum of the clinical programme. As Helsinn broadens its focus beyond cancer supportive care and into cancer therapeutics, high quality partnerships such as our collaboration with MEI Pharma are key for Helsinn to create value and benefit more people with cancer."

"The initiation of this highly anticipated study is the culmination of diligent preparation in collaboration with our partners at Helsinn," said Daniel P. Gold, Ph.D., President and Chief Executive Officer of MEI Pharma. "AML is a rapidly progressing, often fatal disease, and patients who are unable to undergo intensive therapies are in urgent need of new treatment options. We believe that with the well-powered, rigorously designed Phase 3 study underway, pracinostat is now one pivotal step closer to serving this need. Meanwhile, enrollment in our Phase 2 dose-optimization study of pracinostat and azacitidine in myelodysplastic syndrome (MDS) continues as planned and we look forward to reporting interim data from the MDS study early next year."

The Phase 3 study of pracinostat in combination with azacitidine is open to adult patients with newly diagnosed AML who are unfit to receive standard induction chemotherapy due to age ≥ 75 years or predefined co-morbidities. Treatments will be administered based on 28-day cycles, with pracinostat or placebo administered orally once every other day, 3 times a week for 3 weeks, followed by one week of no treatment and azacitidine administered for 7 days of each cycle. Additional information regarding the study, including detailed inclusion and exclusion criteria, is available at ClinicalTrials.gov (identifier: NCT03151408).

Results from a Phase 2 open-label, single-arm, multicenter study of pracinostat and azacitidine in 50 patients aged ≥ 65 years with newly diagnosed AML not eligible for induction chemotherapy showed a median overall survival of 19.1 (95%CI: 10.0-26.5) months, one-year survival of 62% and a CR rate of 42%. Responses were durable (median CR+CRi 17.2 months). Blast clearance was rapid (median 8 weeks) while CR required prolonged therapy (>6 months) in some patients. The combination of pracinostat and azacitidine had no unexpected toxicities. The most common grade 3/4 treatment-emergent adverse events reported in >10% of all patients included thrombocytopenia, febrile neutropenia, neutropenia, fatigue and anemia. These results were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2016.

About AML
AML is the most common acute leukemia affecting adults, and its incidence is expected to continue to increase as the population ages. The American Cancer Society estimates about 21,380 new cases and 10,590 deaths from AML in the U.S. for 2017; the average age of a patient with AML is about 67 years. According to the Surveillance of Rare Cancers in Europe project, the incidence of AML in Europe is 3.7 per 100,000. There are currently no drugs approved in the U.S. to treat AML in patients who are unfit for intensive induction chemotherapy, though hypomethylating agents are recommended by the National Comprehensive Cancer Network (NCCN) guidelines. In the EU, azacitidine is approved for the treatment of adult patients aged 65 years or older who are not eligible for hematopoietic stem cell transplant (HSCT) with AML with >30% marrow blasts according to the World Health Organization (WHO) classification.

About Pracinostat
Pracinostat is an oral histone deacetylase (HDAC) inhibitor that is in late-stage clinical development. The U.S. Food and Drug Administration has granted Breakthrough Therapy Designation for pracinostat in combination with azacitidine for the treatment of patients with newly diagnosed AML who are ≥75 years of age or unfit for intensive chemotherapy. In August 2016, Helsinn and MEI Pharma entered into an exclusive license, development and commercialization agreement for pracinostat in AML and other potential indications. Under the terms of the agreement, Helsinn is granted a worldwide exclusive license to develop, manufacture and commercialize pracinostat, and is primarily responsible for funding its global development and commercialization. Pracinostat is an investigational agent and is not approved for commercial use in the U.S.

Kite Doses First Patient in the Phase 2 Trial of Axicabtagene Ciloleucel in Indolent B-Cell Non-Hodgkin Lymphoma (ZUMA-5)

On August 2, 2017 Kite Pharma, Inc., (Nasdaq:KITE), a leading cell therapy company, reported that patients with relapsed/refractory indolent B-cell non-Hodgkin lymphoma (iNHL) are now being treated in its Phase 2 ZUMA-5 trial with its lead investigational candidate, axicabtagene ciloleucel (axi-cel) (Press release, Kite Pharma, AUG 2, 2017, View Source [SID1234519984]). This study builds upon early clinical results using the same axi-cel anti-CD19 construct previously published in the March 2012 issue of Blood, "B-cell Depletion and Remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells,"1 in which patients with relapsed/refractory iNHL experienced a high response rate and durable disease remissions in a clinical trial at the National Cancer Institute (NCI).

"Despite recent advances in the treatment of NHL, iNHL generally remains an incurable disease. As a result, there is a great unmet need in patients with high-risk disease which is why the focus of this study has the opportunity to make a difference," said David Chang, M.D., Ph.D., Executive Vice President of Research and Development and Chief Medical Officer of Kite. "The dosing of the first patient in ZUMA-5 marks an important milestone in our commitment to serving patients. We will continue to explore the potential for axi-cel to treat hematologic malignancies beyond aggressive NHL, the foundation of our CAR-T program."

B-cell iNHL is expected to account for approximately 25 percent of 2017 newly diagnosed NHL cases in the United States (U.S.). Follicular lymphoma is the most common type of iNHL and one of the most common subtypes of NHL. The company estimates that there will be approximately 4,700 patients in 2017 with follicular lymphoma in the U.S. who could potentially benefit from CAR-T therapy.

ZUMA-5 is a single-arm, open-label, multi-center study in patients with iNHL whose disease has relapsed within two years of first line treatment, is refractory to second line or greater therapy or has relapsed at any point after transplant. The study will enroll approximately 50 patients. Additional details about this study can be found on ClinicalTrials.gov, using identifier NCT: 03105336.

About axicabtagene ciloleucel

Kite’s lead product candidate, axicabtagene ciloleucel is an investigational therapy in which a patient’s T cells are engineered to express a chimeric antigen receptor (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. Axicabtagene ciloleucel is currently under review by the U.S. Food and Drug Administration (FDA) for aggressive non-Hodgkin’s lymphoma and was granted Breakthrough Therapy Designation status for diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL).

Celsion Announces Latest Translational Data from the OVATION Study in Newly Diagnosed Advanced Ovarian Cancer Patients

On August 2, 2017 Celsion Corporation (NASDAQ:CLSN) reported findings from the translational research data from its Phase Ib dose escalating clinical trial (the OVATION Study) combining GEN-1, the Company’s IL-12 gene-mediated immunotherapy, with the standard of care for the treatment of newly-diagnosed patients with Stage III and IV ovarian cancer who will undergo neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (Press release, Celsion, AUG 2, 2017, View Source [SID1234519983]).

Translational research data was reviewed with leading immuno-oncology experts from the Roswell Park Cancer Institute. The analysis of peritoneal fluid and blood samples collected immediately before and 24 hours after IP administration of multiple doses of GEN-1 (36, 47, 61, 72 mg/m2) and standard NACT (carboplatin every 21 days and Taxol weekly) shows clear evidence of IL-12 gene transfer by dose dependent increases in IL-12 levels and immune system activity and significant increases in interferon-gamma (IFN- γ) and decreases in VEGF levels. The treatment-related changes in immune activating cytokines and pro-tumor VEGF levels followed a dose-dependent trend and were predominantly in the peritoneal fluid compartment with little to no changes observed in the patients’ systemic blood stream.

Key translational research findings from the first 12 of 15 patients&supl; enrolled in four patient cohorts are summarized below:
The treatment-related changes in immune activating cytokines and pro-tumor VEGF and IFN- γ levels followed a dose-dependent trend and were predominantly in the peritoneal fluid compartment with little to no changes observed in the patients’ systemic circulation. The observed immunological changes are consistent with an IL-12 based mechanism.

Effects observed in the IHC analysis were pronounced decreases in the density of immunosuppressive T-cell signals (FoxP3, PD-1, PDL-1, IDO-1) and increases in CD8+ cells in the tumor microenvironment.

The ratio of CD8+ cells to immunosuppressive cells was increased in approximately 75% of patients suggesting an overall shift in the tumor microenvironment from immunosuppressive to pro-immune stimulatory following treatment with GEN-1. An increase in CD8+ to immunosuppressive T-cell populations is a leading indicator and believed to be a good predictor of improved overall survival.

"These translational research findings demonstrate that GEN-1 in ovarian cancer patients is biologically active and creates a shift in the tumor microenvironment in the peritoneal cavity in a dose-dependent manner and promotes a pro-immune T-cell population dynamic in the tumor microenvironment," said Dr. Khursheed Anwer, Celsion’s executive vice president and chief science officer. "These distinct immunological changes in the local disease environment appear to translate into clinical benefit and warrant the continued development of our GEN-1 IL-12 immunotherapy as a potential adjuvant, in both first and second-line ovarian cancer. Furthermore, pro-immune changes in the tumor microenvironment appear to support research combining GEN-1 with other exciting immuno-oncology therapies including adaptive T-cell and check point inhibitors."

The Company previously announced the latest clinical findings from the OVATION Study in a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2017 Annual Meeting in June 2017. The presentation summarized clinical findings for all fourteen patients treated in the trial to-date.

Of the fourteen patients treated to date, two (2) patients demonstrated a complete response, ten (10) patients demonstrated a partial response and two (2) patients demonstrated stable disease, as measured by RECIST criteria.
This translates to a 100% disease control rate (DCR) and an 86% objective response rate (ORR).

Of the five patients treated in the highest dose cohort, there was a 100% objective response rate with one (1) complete response and four (4) partial responses.

Fourteen patients had successful resections of their tumors, with nine (9) patients (64%) having an R0 resection, which indicates a margin-negative resection in which no gross or microscopic tumor remains in the tumor bed.

Of the five patients treated at the highest dose cohort, all five patients (100%) experienced a R0 surgical resection.

Seven out of eight (87%) patients in the highest two dose cohorts experienced a R0 surgical resection.

Of the seven patients who have received GEN-1 treatment over one year ago and are being followed, only one patient’s cancer has progressed after 11.7 months. This compares favorably to the historical median progression free survival (PFS) of 12 months for newly-diagnosed patients with Stage III and IV ovarian cancer that undergo neoadjuvant chemotherapy followed by interval debulking surgery². Of the remaining six patients who have been on the study for over one year, their average PFS is 16.4 months with the longest progression-free patient at over 22 months.

"The impressive early trends in tumor response, surgical resections and progression-free survival are consistent with the dose dependent increases in IFN- γ levels, decreases in VEGF levels and immune system activity observed in the translational data," said Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "Ovarian cancer patients have a very poor prognosis. These data along with other published, pre-clinical data, underscore the potential of GEN-1 to serve as an effective, safe IL-12 immunotherapy in this underserved population."

CTI BioPharma Announces Completion of Enrollment in the Phase 3 PIX306 Trial of PIXUVRI® for Aggressive B-cell non-Hodgkin lymphoma

On August 2, 2017 CTI BioPharma Corp. (NASDAQ and MTA: CTIC) reported the completion of enrollment in the Phase 3 PIX306 trial of PIXUVRI (pixantrone) (Press release, CTI BioPharma, AUG 2, 2017, View Source [SID1234519970]). The PIX306 trial is evaluating PIXVURI combined with rituximab in comparison to that of rituximab combined with gemcitabine in patients with aggressive B-cell non-Hodgkin lymphoma (NHL). Patients eligible to be enrolled in the trial had failed front line CHOP-R and were not eligible for autologous stem cell transplant (ASCT) (2nd line) or failed ASCT (3rd or 4th line). PIXUVRI has previously been granted conditional marketing authorization from the European Commission for the treatment of adult patients with multiply relapsed or refractory aggressive B-cell NHL.i The trial is being conducted as a post-authorization requirement of conditional marketing authorization. If positive, the results from this trial could support broader indications. Top-line results are event-driven and are expected in the first half of 2018.

About PIXUVRI (pixantrone)

PIXUVRI is a cytotoxic medicine that works by interfering with the DNA within cells and preventing them from making more copies of DNA. This means that the cancer cells in B-cell NHL cannot divide and eventually die.ii

PIXUVRI is conditionally approved in the EU as monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive B-cell NHL. The benefit has not been established in patients when used as fifth line or greater chemotherapy in patients who are refractory to last therapy.

The Summary of Product Characteristics (SmPC) has the full prescribing information, including the safety and efficacy profile of PIXUVRI in the approved indication. The SmPC is available at www.servier.com.

About NHL

NHL is an uncommon type of cancer that affects the lymphatic system, which is defined as a network of vessels and glands that run throughout the body.iii The lymphatic system is a key component of the immune system, as it plays a role in destroying old or abnormal cells and fighting bacteria and other infections.iv

Around 93,500 new cases of NHL were diagnosed in Europe in 2012, making it the eleventh most common cancer on the continent.v

NHL comprises more than 60 subtypes, with each requiring a different diagnostic evaluation and treatment approaches. Lymphoma patient groups around the world, led by the umbrella group Lymphoma Coalition, have been recently calling for accurate subtype reporting to allow patients to clearly understand their subtype and have better communication with their doctors. Given the complexities of the condition, access to information is essential to empower patients.