On October 4, 2018 Delcath Systems, Inc. (OTCQB: DCTH), an interventional oncology company focused on the treatment of primary and metastatic cancers of the liver, reported that results of a multicenter analysis of outcomes in patients with intrahepatic cholangiocarcinoma (ICC) treated with CHEMOSAT has been published in the journal European Radiology (Press release, Delcath Systems, OCT 4, 2018, View Source;p=RssLanding&cat=news&id=2370255 [SID1234529788]). The study is the first analysis on the use of Delcath’s PHP Therapy for the treatment of ICC.

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The retrospective analysis—Percutaneous Hepatic Perfusion (Chemosaturation) with Melphalan in Patients with Intrahepatic Cholangiocarcinoma: European Multicentre Study on Safety, Short Term Effects and Survival—was conducted by investigators in Germany, Italy, Netherlands, Spain and France with Dr. Steffen Marquardt of Hannover Medical School serving as lead author. The study evaluated 15 patients with ICC who were selected for PHP treatment after failing prior therapies. The patients were treated at nine hospitals throughout Europe between 2012 and 2016. Treatment outcomes were assessed by imaging every three months following PHP treatment.

Results of the study showed that after the first PHP treatment, one patient (7%) has a complete response (CR), two patients (13%) had a partial response (PR), and stable disease (SD) was observed in eight patients (53%). This equates to a control rate (CR+PR+SD) of 73%. The complete response patient was not retreated and is still alive. Three patients (20%) progressed after the first treatment and one patient died prior to post-procedure imaging. Five of the patients with SD received a second PHP treatment, resulting in one PR (20%), three SD (60%), and one PD (20%). During the follow-up phase two of the SD patients received additional PHP treatments.

Median overall survival (OS) was 26.9 months from initial diagnosis and 7.6 months from first PHP treatment. One-year OS from first PHP was 40%. Median progression free survival (PFS) was 122 days, and median hepatic progression free survival (hPFS) was 131 days.

In this retrospective data collection, side-effects were potentially under-reported but were considered by the investigators to be tolerable and comparable to other systemic and local therapies. Nevertheless, in the context of the patient selection, baseline characteristics and number of PHP treatments provided in this retrospective study, practitioners observed no adverse events of grades 3 or 4 severity during the PHP procedure. Post-procedurally, significant hematological toxicity was observed in the form of anemia and thrombocytopenia 5-7 days after the PHP procedure. Management with Granulocyte Colony Stimulating Factor (GCSF) was employed in some patients. These toxicities were considered consistent with those toxicities reported in the ABC 02 trial of systemic chemotherapy in this patient population.

Investigators concluded that PHP Therapy provides "promising response rates in patients with ICC," and that side-effects were tolerable and comparable to other treatment strategies.

Commenting on the study, Jennifer K. Simpson, PhD, MSN, CRNP, President & CEO of Delcath Systems, said, "Results of this study are very encouraging when you consider that PHP Therapy was used for these patients after failing prior therapy(ies) and that all patients had been heavily pre-treated. Additionally, many of the patients included in this retrospective analysis were treated before certain aspects of the PHP procedure had become standard, such as the prophylactic use of GCSF growth factors to mitigate certain side-effects. These data have been previously used to inform the trial design for our Phase 3 trial in ICC, and we look forward to further investigating the use of PHP Therapy in a disease that has particularly challenging patient outcomes."

On October 4, 2018 Halozyme Therapeutics, Inc. (NASDAQ: HALO), a biotechnology company developing novel oncology and drug-delivery therapies, reported the publication of nonclinical data for PEGPH20 in Clinical Cancer Research, an American Association for Cancer Research (AACR) (Free AACR Whitepaper) journal (Press release, Halozyme, OCT 4, 2018, View Source [SID1234529759]). PEGPH20 is the PEGylated version of Halozyme’s proprietary recombinant human hyaluronidase enzyme, rHuPH20, that temporarily degrades hyaluronan (HA). HA is a naturally occurring glycosaminoglycan that can accumulate in the tumor microenvironment (TME) of certain solid tumor types.

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The paper further characterizes the biological and physical changes associated with HA-accumulating (HA-high) tumors in mouse models demonstrating an association with increased collagen content, high tumor interstitial pressure (tIP), vascular collapse, hypoxia, drug resistance and increased metastatic potential. Treatment with PEGPH20 at the human equivalent dose degraded HA in the TME reversing these changes, and also depleted an important proangiogenic growth factor, VEGF-A165, suggesting that treatment with PEGPH20 may diminish the angiogenic potential of the TME.

"The publication of this preclinical work highlights PEGPH20’s encouraging anti-tumor activity profile through the degradation of hyaluronan. In addition, for the first time, it presents evidence that PEGPH20 depletes stores of VEGF-A165, a key proangiogenic growth factor, suggesting that PEGPH20 may diminish the angiogenic potential of the tumor microenvironment," said Dr. Helen Torley, president and chief executive officer. "These data expand our understanding of the PEGPH20 mechanism of action and provide additional support for the potential for meaningful clinical responses in high hyaluronan accumulating tumors."

The accumulation of HA is common in many cancers, particularly in pancreatic cancer where increased HA accumulation predicts a less favorable outcome. A Phase 3 study evaluating the ability of PEGPH20 plus Abraxane (nab-paclitaxel) and gemcitabine to increase Progression Free Survival and Overall Survival versus Abraxane and gemcitabine alone in metastatic pancreatic ductal adenocarcinoma patients, is under way.

Key findings from the Clinical Cancer Research publication included:

Accumulation of HA in tumors correlated with high tIP, vascular collapse, hypoxia, drug resistance and increased metastatic potential
HA accumulation also correlated with increased collagen content and was associated with an increase in α-SMA
Remodeling of the tumor microenvironment is mediated by the enzymatic removal of tumor HA
Treatment with PEGPH20 at the human equivalent dose depleted tumor-associated VEGF-A165 to an undetectable level potentially reducing the angiogenic potential of the TME
The paper, titled "Parallel Accumulation of Tumor Hyaluronan, Collagen, and Other Drivers of Tumor Progression" was published online in Clinical Cancer Research on September 27, 2018.

On October 4, 2018 Heat Biologics, Inc. (NASDAQ: HTBX), a biopharmaceutical company developing drugs designed to activate a patient’s immune system against cancer, and its Pelican Therapeutics subsidiary ("Pelican") reported updates its novel PTX-35 co-stimulatory antibody (Press release, Heat Biologics, OCT 4, 2018, View Source [SID1234529923]). PTX-35 is designed to harness the body’s natural antigen-specific immune activation mechanisms. When combined with immunotherapies, including checkpoint inhibitors as well as Heat’s ImPACT and ComPACT technologies, PTX-35 has been shown to enhance antigen-specific T-cell activation to eliminate tumor cells in pre-clinical models.

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Recent PTX-35 highlights:

Completed cell line development and creation of validated master cell bank for cGMP manufacturing
Established CMC path for the production of GMP clinical material and non-clinical preliminary pharmacology / non-GLP toxicology studies
Preliminary non-GLP pharmacology demonstrates positive results, including efficient binding and activation on cells expressing the TNFRSF25 receptor, as well as increased expansion of T-cells in-vivo
2-week IND enabling dose range finding toxicology studies in primates receiving two doses show no signs or signals of clinical toxicity across wide dose range
Ongoing pre-IND discussions with FDA; expect to submit IND in Q1 2019
Rahul Jasuja, Ph.D., CEO of Pelican, commented, "We are progressing rapidly with our pre-clinical activities and expect to submit an IND for PTX-35 in the first quarter of 2019. We are strongly encouraged by the preliminary pre-clinical efficacy and safety data which shows no signs of toxicity across a wide range of doses."

Dr. Jasuja continued, "We have been efficient in our use of funds, which has allowed us to come in under budget, further extending our runway for this program. Given our operating efficiency thus far, we expect to receive the next tranche of grant funding once we fully utilize the funds that the Cancer Prevention Research Institute of Texas ("CPRIT") has previously provided. As we progress, our plan is to advance a broad clinical development program that could include combination therapy with Heat’s ImPACT and ComPACT therapies, as well as other costimulatory agonists, checkpoint inhibitors and immune modifiers to address the unmet need for patients who do not respond well to current cancer therapies."

The Company further reported that PTX-35 was featured in Nature’s Biopharma Dealmakers September 2018 edition, which is available at: View Source

To-date, Pelican has received $8.3 million in grants from CPRIT. The CPRIT award supports pre-clinical development, manufacturing and clinical development through a comprehensive 70-patient Phase 1 clinical trial for PTX-35. The Company expects to meet the qualifications to receive the third tranche of its $15.2 million CPRIT grant award, totaling $6.9 million, later this year.

On October 4, 2018 Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD), a clinical-stage biopharmaceutical company focused on the development of specialized CAR-T cell-based therapies, reported that clinical and preclinical data on the company’s pipeline of candidates will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting being held November 7-11, 2018, in Washington, D.C (Press release, Celyad, OCT 4, 2018, View Source [SID1234529760]). Ten different abstracts have been selected by the SITC (Free SITC Whitepaper) Program Committee attesting to a vigorous and ambitious research program.

"We view SITC (Free SITC Whitepaper) 2018 as an important meeting for a number of reasons", said David Gilham, Ph.D., VP of Research and Development at Celyad. "Firstly, we will provide a clinical update on our CYAD-01 program in solid tumors. Secondly, we will share how we’ve continued to develop the early academic NKG2D CAR-T asset into the commercially feasible clinical entity CYAD-01. We will provide an update on our next generation CAR-T pipeline, and in particular on our non-gene edited allogeneic CAR-T program. We believe we are on a trajectory to be a leading player in the autologous and allogeneic CAR-T cell therapy landscape in the years to come."

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On October 4, 2018 Pfizer Inc. reported the recipients of the Advancing Science through Pfizer Investigator Research Exchange (ASPIRE) Breast Cancer Research Awards (Press release, Pfizer, OCT 4, 2018, View Source [SID1234529942]). Four grants totaling more than $3 million (USD) in funding will be awarded to investigators in the United States (U.S.) to support clinical research projects involving Pfizer compounds in breast cancer. Since 2015, Pfizer has provided more than $16 million in total funding for the ASPIRE Oncology Research Awards Program across breast and hematologic cancers.

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"The ASPIRE awards underscore Pfizer’s commitment to collaborating with investigators to expand scientific knowledge and improve the treatment of breast cancer," said Lynn McRoy, M.D., breast cancer lead, U.S. Medical Affairs, Pfizer Oncology. "The recipients of the 2018 awards submitted outstanding clinical research proposals that have the potential to advance care for people living with breast cancer."

Recipients of the 2018 awards were selected through a competitive application process overseen by an independent review panel of experts. The following investigators and studies have been selected to receive grants:

Dr. Mylin A. Torres, Glenn Family Breast Center, Winship Cancer Institute, Emory University – A Phase 2 Multi-institutional Study of Concurrent Radiotherapy, Palbociclib, and Hormone Therapy for Treatment of Bone Metastasis in Breast Cancer Patients
Dr. Aditya Bardia, Massachusetts General Hospital Cancer Center – Evaluation of Talazoparib, a PARP Inhibitor, for Patients With Somatic BRCA Mutant Metastatic Breast Cancer in a Genotyping Based Clinical Trial
Dr. Antoinette Tan, Levine Cancer Institute, Atrium Health – IGNITE-Immunoprofiling of Gedatolisib, a Dual PI3-Kinase and mTOR Inhibitor, in the Neo-Immunoadjuvant Treatment of Early Stage Breast Cancer
Dr. Kari Wisinski, University of Wisconsin Carbone Cancer Center – Phase 2 Trial with Safety Run-In of Gedatolisib Plus Talazoparib in Advanced Triple Negative or BRCA1 or 2 Positive, HER2 Negative Breast Cancers
Investigators in the U.S. were encouraged to submit proposals for the 2018 ASPIRE Breast Cancer Research Awards that advance knowledge in the treatment and disease management of breast cancer. Proposals were eligible for IBRANCE (palbociclib), an oral, first-in-class inhibitor of cyclin-dependent kinases (CDKs) 4 and 6, for metastatic breast cancer, the most advanced stage of breast cancer (stage IV)1,2; talazoparib, an investigational, once-daily, oral poly ADP ribose polymerase (PARP) inhibitor; and gedatolisib (PF-05212384), an investigational, small molecule, dual inhibitor targeting the phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) signaling pathways in the development of solid tumors.

For more information about ASPIRE, please visit www.aspireresearch.org.

About IBRANCE (palbociclib) 125 mg capsules
IBRANCE is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer in combination with an aromatase
inhibitor as initial endocrine based therapy in postmenopausal women, or fulvestrant in women with disease progression following endocrine
therapy.

IMPORTANT IBRANCE (palbociclib) SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

Neutropenia was the most frequently reported adverse reaction in PALOMA-2 (80%) and PALOMA-3 (83%). In PALOMA-2, Grade 3 (56%) or 4 (10%) decreased neutrophil counts were reported in patients receiving IBRANCE plus letrozole. In PALOMA-3, Grade 3 (55%) or Grade 4 (11%) decreased neutrophil counts were reported in patients receiving IBRANCE plus fulvestrant. Febrile neutropenia has been reported in 1.8% of patients exposed to IBRANCE across PALOMA-2 and PALOMA-3. One death due to neutropenic sepsis was observed in PALOMA-3. Inform patients to promptly report any fever.

Monitor complete blood count prior to starting IBRANCE, at the beginning of each cycle, on Day 15 of first 2 cycles and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

Based on the mechanism of action, IBRANCE can cause fetal harm. Advise females of reproductive potential to use effective contraception during IBRANCE treatment and for at least 3 weeks after the last dose. IBRANCE may impair fertility in males and has the potential to cause genotoxicity. Advise male patients with female partners of reproductive potential to use effective contraception during IBRANCE treatment and for 3 months after the last dose. Advise females to inform their healthcare provider of a known or suspected pregnancy. Advise women not to breastfeed during IBRANCE treatment and for 3 weeks after the last dose because of the potential for serious adverse reactions in nursing infants.

The most common adverse reactions (≥10%) of any grade reported in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (80% vs 6%), infections (60% vs 42%), leukopenia (39% vs 2%), fatigue (37% vs 28%), nausea (35% vs 26%), alopecia (33% vs 16%), stomatitis (30% vs 14%), diarrhea (26% vs 19%), anemia (24% vs 9%), rash (18% vs 12%), asthenia (17% vs 12%), thrombocytopenia (16% vs 1%), vomiting (16% vs 17%), decreased appetite (15% vs 9%), dry skin (12% vs 6%), pyrexia (12% vs 9%), and dysgeusia (10% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia (66% vs 2%), leukopenia (25% vs 0%), infections (7% vs 3%), and anemia (5% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-2 for IBRANCE plus letrozole vs placebo plus letrozole were decreased WBC (97% vs 25%), decreased neutrophils (95% vs 20%), anemia (78% vs 42%), decreased platelets (63% vs 14%), increased aspartate aminotransferase (52% vs 34%), and increased alanine aminotransferase (43% vs 30%).

The most common adverse reactions (≥10%) of any grade reported in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%), stomatitis (28% vs 13%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16% vs 8%), and pyrexia (13% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were neutropenia (66% vs 1%) and leukopenia (31% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-3 for IBRANCE plus fulvestrant vs placebo plus fulvestrant were decreased WBC (99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%), decreased platelets (62% vs 10%), increased aspartate aminotransferase (43% vs 48%), and increased alanine aminotransferase (36% vs 34%).

Avoid concurrent use of strong CYP3A inhibitors. If patients must be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg. If the strong inhibitor is discontinued, increase the IBRANCE dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit juice may increase plasma concentrations of IBRANCE and should be avoided. Avoid concomitant use of strong CYP3A inducers. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced as IBRANCE may increase their exposure.

For patients with severe hepatic impairment (Child-Pugh class C), the recommended dose of IBRANCE is 75 mg. The pharmacokinetics of IBRANCE have not been studied in patients requiring hemodialysis.