On August 24, 2017 Celsion Corporation (NASDAQ:CLSN), an oncology drug development company, reported an update on its OVATION Study, a Phase Ib dose escalating clinical trial combining GEN-1, the Company’s DNA-based immunotherapy, with the standard of care for the treatment of newly-diagnosed patients with advanced (stage III/IV) ovarian cancer who will undergo neoadjuvant chemotherapy followed by interval debulking surgery (Press release, Celsion, AUG 24, 2017, View Source [SID1234520311]). GEN-1 is an IL-12 DNA plasmid vector formulated as a nanoparticle in a non-viral delivery system to cause the sustained local production and secretion of the Interleukin-12 (IL-12) protein loco-regionally to the tumor site.

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The Company announced that an abstract for the OVATION Study has been accepted for presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Addressing Critical Questions in Ovarian Cancer Research and Treatment Special Conference, which will take place from October 1 – 4, 2017 at the Wyndham Grand Pittsburgh Downtown in Pittsburgh, PA.

The abstract, entitled "Immunological changes following intraperitoneal administration of a formulated IL-12 plasmid in combination with neoadjuvant chemotherapy in newly diagnosed advanced ovarian cancer patients," will be presented in a poster presentation session by Dr. Khursheed Anwer, Celsion’s executive vice president and chief scientific officer.

The presentation will summarize clinical findings and translational data from all patients treated in the Phase Ib dose escalating clinical trial. The translational data provides further insight into GEN-1’s mechanism of action through the evaluation of dose-related changes in the tumor and peritoneal immune cell population, as well as through the peritoneal cytokine levels.

Celsion previously reported highly encouraging clinical data from the first fourteen patients who have completed treatment in the OVATION Study. GEN-1 plus standard chemotherapy produced positive clinical results, with no dose limiting toxicities and promising dose dependent efficacy signals which correlate well with successful surgical outcomes as summarized below:
Of the fourteen patients treated to date in the entire study, 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 microscopically margin-negative resection in which no gross or microscopic tumor remains in the tumor bed. Seven out of eight (87%) patients in the highest two dose cohorts experienced a R0 surgical resection. All five patients treated at the highest dose cohort experienced a R0 surgical resection.

All patients experienced a clinically significant decrease in their CA-125 protein levels as of their most recent study visit. CA-125 is used to monitor certain cancers during and after treatment. CA-125 is present in greater concentrations in ovarian cancer cells than in other cells.

Of the eight patients who have received GEN-1 treatment over one year ago and are being followed, only two patients’ cancer has progressed. 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 surgery. Of the remaining six patients who have been on the study for over one year, their average PFS as of this date is 17 months with the longest progression-free patient at 23 months.

"We have completed enrollment of our OVATION Study in newly diagnosed ovarian cancer patients, one goal of which is to determine GEN-1’s activity in combination with standard chemotherapy. The remarkable surgical outcomes among all patients completing the prescribed eight weekly treatments reinforce our confidence in the promise of GEN-1’s ability to work safely and effectively in advanced ovarian cancer," said Michael H. Tardugno, Celsion’s chairman, president and CEO. "We have scheduled an Advisory Board Meeting in late September 2017 with our clinical investigators and scientific experts from the Roswell Park Cancer Institute and M.D. Anderson Cancer Center to review the clinical and translational research data from the OVATION Study in order to determine the next steps forward for this exciting new immunotherapy. With the endorsement and recommendations from the Advisory Board, we fully expect to file a next phase protocol with FDA later this year."

OVATION Study Design
The Phase Ib trial will evaluate weekly intraperitoneal dosing of GEN-1 in combination with neoadjuvant chemotherapy, the standard of care for patients newly diagnosed with ovarian cancer. Concurrently with neoadjuvant chemotherapy, enrolled patients will receive escalating weekly doses of GEN-1, from levels beginning at 36mg/m², to 47mg/m², 61mg/m² and 79mg/m² weekly for 8 treatments in total, with interval debulking surgery to follow. The regimen will primarily be evaluated for its safety and tolerability.

About GEN-1 Immunotherapy
GEN-1, designed using Celsion’s proprietary TheraPlas platform technology, is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anti-cancer immunity acting through the induction of T-lymphocyte and natural killer (NK) cell proliferation. The Company has previously reported positive safety and encouraging Phase I results with GEN-1 given as monotherapy in patients with peritoneally metastasized ovarian cancer, and recently completed a Phase Ib trial of GEN-1 in combination with PEGylated doxorubicin in patients with platinum-resistant ovarian cancer.

On August 24, 2017 Novartis reported that the European Commission (EC) approved Kisqali (ribociclib) in combination with an aromatase inhibitor for treatment of postmenopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) locally advanced or metastatic breast cancer as initial endocrine-based therapy (Press release, Novartis, AUG 24, 2017, View Source [SID1234520306]). Kisqali is the first CDK4/6 inhibitor approved in Europe based on a first-line Phase III trial that met its primary endpoint of progression-free survival (PFS) at interim analysis.

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"This approval of Kisqali reinforces our recognized leadership in cancer research and our commitment to innovative targeted therapies," said Bruno Strigini, CEO, Novartis Oncology. "We are proud of our collaboration with study investigators and patients, which provides the medical community with an important new treatment option for women with advanced or metastatic breast cancer."

EU approval follows a positive opinion granted in June by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), which was based on superior efficacy and demonstrated safety of Kisqali plus letrozole versus letrozole alone in the pivotal Phase III MONALEESA-2 trial. The opinion included a recommendation that allows oncologists the flexibility to prescribe Kisqali with any aromatase inhibitor (i.e., letrozole, anastrozole or exemestane) they deem most appropriate for their patient.

"Advanced breast cancer remains incurable, so it’s important to start with a powerful treatment option at initial diagnosis," said Wolfgang Janni, MD, PhD, University of Ulm, MONALEESA-2 investigator. "I am encouraged that women in Europe living with HR+/HER2- advanced breast cancer may be treated in first-line with ribociclib in combination with letrozole, which demonstrated strong progression-free survival of more than two years in the pivotal MONALEESA-2 trial."

MONALEESA-2 enrolled 668 postmenopausal women with HR+/HER2- advanced or metastatic breast cancer who received no prior systemic therapy for their advanced breast cancer and showed that Kisqali plus letrozole, an aromatase inhibitor, reduced the risk of progression or death by 43% over letrozole alone (median PFS=25.3 months (95% CI: 23.0-30.3) vs. 16.0 months (95% CI: 13.4-18.2); HR=0.568 (95% CI: 0.457-0.704; p<0.0001)[1]. More than half of patients (55%) with measurable disease taking Kisqali plus letrozole experienced a tumor reduction of at least 30 percent[1].

Up to one-third of patients with early-stage breast cancer will subsequently develop advanced disease, for which there is currently no cure[3]. Globally approximately 250,000 women are diagnosed with advanced breast cancer each year[4].

Kisqali can be taken orally once-daily with or without food at a suggested starting dose of 600 mg (three 200 mg tablets) for three weeks, followed by one week off treatment. Kisqali is taken in combination with continuous use of any aromatase inhibitor.

This decision is applicable to all 28 European Union member states plus Iceland, Norway and Liechtenstein. Additional regulatory filings are underway with other health authorities worldwide.

In March 2017, the US Food and Drug Administration (FDA) approved Kisqali, in combination with any aromatase inhibitor, as a treatment for metastatic breast cancer. Ribociclib in combination with letrozole was added to the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) as a category 1 option for HR+/HER2- postmenopausal metastatic breast cancer patients[5].

About Kisqali (ribociclib)
Kisqali (ribociclib) is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably.

Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.

About the Kisqali Clinical Trial Program
Novartis is continuing to assess Kisqali through the robust MONALEESA clinical trial program, which includes two additional Phase III trials, MONALEESA-3 and MONALEESA-7 that are evaluating Kisqali in combination with multiple endocrine therapy partners across a broad range of patients, including premenopausal women. MONALEESA-3 is evaluating Kisqali in combination with fulvestrant compared to fulvestrant alone in postmenopausal women with HR+/HER2- advanced breast cancer who have received no or a maximum of one prior endocrine therapy. MONALEESA-7 is investigating Kisqali in combination with endocrine therapy and goserelin compared to endocrine therapy and goserelin alone in premenopausal women with HR+/HER2- advanced breast cancer who have not previously received endocrine therapy. These trials are fully enrolled.

Novartis is initiating two multi-center, randomized, double-blind Phase III clinical trials, EarLEE-1 and EarLEE-2, to evaluate the safety and efficacy of Kisqali with endocrine therapy as adjuvant therapy in pre- and postmenopausal women who have not previously received treatment with CDK4/6 or aromatase inhibitors. EarLEE-1 aims to assess Kisqali with adjuvant endocrine therapy compared to adjuvant endocrine therapy alone in women with HR+/HER2- high-risk early breast cancer. EarLEE-2 will investigate Kisqali with adjuvant endocrine therapy compared to adjuvant endocrine therapy alone in women with HR+/HER2- intermediate-risk early breast cancer.

The CompLEEment-1 study is evaluating the safety and efficacy of Kisqali plus letrozole in men and pre- or postmenopausal women with HR+/HER2- advanced breast cancer with no prior hormonal therapy for advanced disease. The open-label, multicenter, Phase IIIb CompLEEment-1 trial is currently enrolling participants.

About Novartis in Advanced Breast Cancer
For more than 25 years, Novartis has been at the forefront of driving scientific advancements for breast cancer patients and improving clinical practice in collaboration with the global community. With one of the most diverse breast cancer pipelines and the largest number of breast cancer compounds in development, Novartis leads the industry in discovery of new therapies and combinations, especially in HR+ advanced breast cancer, the most common form of the disease.

Important Safety Information FROM THE KISQALI EU SmPC
The most common ADRs and the most common grade 3/4 ADRs (reported at a frequency >=20% and >=2% respectively) for which the frequency for Kisqali plus letrozole exceeds the frequency for placebo plus letrozole were blood and lymphatic system disorders (including abnormally low neutrophil and white blood cell count), headache, back pain, nausea, fatigue, diarrhea, vomiting, constipation, hair loss and rash and abnormally low levels of neutrophils or white blood cells, abnormal liver function tests (increased alanine and aspartate aminotransferase), abnormally low lymphocyte count, low levels of phosphate, vomiting, nausea, fatigue and back pain, respectively. Low levels of neutrophils was the most commonly seen severe adverse event; fever in addition to a low neutrophil count was reported in 1.5% of patients.

Kisqali can cause serious side effects such as a significant decrease in neutrophil count, abnormal liver function tests and may have an effect on the electrical activity of the heart known as QT/QTc interval prolongation, which could lead to disturbances in heart rhythm. As a precaution, patients should have complete blood counts, liver function, and serum electrolyte levels measured prior to starting treatment as well as during treatment with Kisqali. Patients should also have their heart activity checked before and monitored during treatment.

The efficacy and safety of ribociclib have not been studied in patients with critical visceral disease.

The use of Kisqali with medicinal products known to prolong QTc interval or strong CYP3A4 inhibitors should be avoided as this may lead to prolongation of the QT/QTc interval. If treatment with a strong CYP3A4 inhibitor cannot be avoided, the Kisqali dose should be reduced. Concomitant administration with other medicines that could affect cardiac repolarization or prolong the QT/QTc interval should be taken into account prior to and during treatment with Kisqali. Patients taking sensitive CYP3A4 substrates with narrow therapeutic index should use caution because of the increased risk of adverse events that may occur if these medications are co-administered with Kisqali.

Kisqali contains soya lecithin and therefore it should not be taken by patients who are allergic to peanut or soya.

Animal studies suggest that Kisqali may cause fetal harm in pregnant women. Therefore, as a precaution, women of childbearing potential should use effective contraception while receiving Kisqali during treatment and up to 21 days after stopping treatment. Women should not breast feed for at least 21 days after the last dose of Kisqali. Kisqali may affect fertility in males.

Please see full Prescribing Information for KISQALI, available at www.kisqali.com

On August 23, 2017 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE:CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address cancer, liver and inflammatory diseases, reported it has received a milestone payment in the amount of $500,000 from Chong Kun Dang Pharmaceuticals (CKD) (Korean Stock Exchange: 185750.KS), which has licensed the exclusive right to distribute Namodenoson (CF102) for the treatment of liver cancer in Korea upon receipt of regulatory approvals (Press release, Can-Fite BioPharma, AUG 23, 2017, View Source [SID1234520309]). This is the second payment received by Can-Fite, as part of the Korean distribution agreement with CKD which is valued at up to $3,000,000 in upfront and milestone payments plus 23% royalties on sales of Namodenoson. Can-Fite has received $1,000,000 to date from CKD and may receive up to an additional $2,000,000 in milestone payments.

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"Namodenoson’s clinical development in the treatment of liver cancer is advancing, as marked by our recent completion of patient enrollment in the U.S., Europe and Israel in our Phase II study of patients with advanced hepatocellular carcinoma with underlying Child-Pugh Class B cirrhosis," stated Can-Fite CEO Dr. Pnina Fishman. "We are pleased to work with CKD in Korea to advance Namodenoson."

Under the distribution agreement with CKD, Can-Fite will supply Namodenoson to CKD, which will be responsible for all costs and activities associated with development, regulatory approvals, marketing, sales and distribution of Namodenoson in Korea. This agreement with CKD marks Can-Fite’s second distribution and licensing deal in Korea, where the Company’s drug candidate Piclidenoson has been out-licensed to Kwang Dong Pharmaceutical Co. for the treatment of rheumatoid arthritis.

51,000 people had liver cancer in Korea, with 11,000 deaths, in 2012 according to a study published in Cancer Research and Treatment: Official Journal of Korean Cancer Association 2015.

About Namodenoson (CF102)

Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson is being evaluated in Phase II trials for two indications, as a second line treatment for hepatocellular carcinoma, and as a treatment for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug. Can-Fite has received Orphan Drug Designation for Namodenoson in Europe and the U.S., as well as Fast Track Status in the U.S. as a second line treatment for hepatocellular carcinoma.

On August 23, 2017 Unum Therapeutics Inc., a clinical stage biopharmaceutical company developing a universal cellular immunotherapy to treat multiple cancers, reported that an investigational new drug (IND) application is now active for ACTR087 T cells in combination with a novel antibody, SEA-BCMA, for the treatment of adult patients with relapsed/refractory multiple myeloma (Press release, Unum Therapeutics, AUG 23, 2017, View Source [SID1234520308]). The IND, which the Company filed in the United States with the Food and Drug Administration, enables Unum to initiate a multi-center Phase 1 trial. This will be the first novel-novel Antibody Coupled T cell receptor (ACTR)-antibody combination. It will also be the first program under Unum’s global collaboration with Seattle Genetics (Nasdaq: SGEN) to enter clinical development, and Unum’s third clinical trial with an ACTR T cell therapy.

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"Despite significant advances in the multiple myeloma field over the past 15 years, there remain significant unmet medical needs in the treatment of the disease, as almost all patients eventually become refractory to therapy"
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"Despite significant advances in the multiple myeloma field over the past 15 years, there remain significant unmet medical needs in the treatment of the disease, as almost all patients eventually become refractory to therapy," said Michael Vasconcelles, MD, Unum’s Chief Medical Officer. "B cell maturation antigen, or BCMA, is considered an attractive therapeutic target for cellular immunotherapies, due to its high and selective expression on the surface of malignant plasma cells in multiple myeloma and its potential role in survival and growth of myeloma cells. We are eager to assess the potential of ACTR087 in combination with SEA-BCMA to become an important new therapy for multiple myeloma patients."
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Site initiation activities are currently underway and the Company anticipates to initiate patient dosing in Q1 2018.
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The ATTCK-17-01 trial is an open-label Phase 1 adaptive dose-escalating study of genetically modified ACTR087 T cells in combination with SEA-BCMA, a novel humanized non-fucosylated anti-BCMA antibody developed using Seattle Genetics’ sugar-engineered antibody (SEA) technology, in patients with relapsed or refractory multiple myeloma. The primary objective of this trial is to evaluate the safety and tolerability of ACTR087 in combination with SEA-BCMA in this study population and determine the recommended Phase 2 dose of the combination. Secondary objectives include patient response measured using the International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma, and ACTR087 persistence, as well as safety and tolerability of SEA-BCMA. The trial will be conducted at several clinical sites in the U.S.
Unum and Seattle Genetics entered into a global strategic collaboration in June 2015, to develop and commercialize novel ACTR combination therapies for cancer.
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About Antibody-Coupled T-cell Receptor (ACTR) Technology
Unum’s proprietary ACTR is a chimeric protein that combines components from receptors normally found on two different human immune cell types – natural killer (NK) cells and T cells – to create a novel approach to cancer cell killing. T cells bearing the ACTR receptor protein can be directed to attack a tumor by combining with a monoclonal antibody that binds antigens on the cancer cell surface.
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In contrast to other T cell therapy approaches for cancer that are limited to a single cancer cell surface target and, therefore, treat a narrow set of tumors, Unum’s approach is not restricted by a specific tumor cell antigen and, thus, may have applications for treating many different types of cancers when combined with the right antibodies.
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Unum is developing ACTR in combination with a range of tumor-targeting antibodies for use in both hematologic and solid tumor indications. ACTR087 in combination with rituximab, an anti-CD20 antibody, is Unum’s most advanced product candidate, currently in Phase I clinical testing for the treatment of adult patients with relapsed/refractory CD20-positive B cell non-Hodgkin lymphoma. ACTR707, is Unum’s second program to enter Phase I clinical testing in combination with rituximab in the same patient population. The Company anticipates that enrollment in this trial will begin in the second half of 2017. ACTR087 in combination with SEA-BCMA will be the Company’s third program to enter clinical development.
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About Multiple Myeloma
Multiple myeloma (MM) is a hematologic malignancy characterized by proliferation of monoclonal plasma cells in the bone marrow and/or extramedullary sites; it accounts for 1.8% of all cancers and approximately 13% of all hematologic malignancies (SEER CSR). The American Cancer Society estimates that in 2017 alone, approximately 30,280 people will be diagnosed with this disease with a higher incidence and prevalence in the elderly. Combination regimens consisting of immunomodulatory agents, proteasome inhibitors and corticosteroids, constitute the backbone of treatment in newly diagnosed MM patients. However, almost all patients with MM who survive initial treatment will eventually relapse and require further therapy. Despite current treatment advances, MM remains largely incurable, necessitating indefinite, sequential therapies and the need for novel therapies in the setting of disease relapse or progression. BCMA (or CD269) has recently emerged as a promising candidate antigen for therapeutic targeting in MM its universal expression on MM cancer cells.