On October 10, 2016 Panther Biotechnology, Inc. reported that a request for a Pre-IND (Investigational New Drug) meeting with the Division of Oncology Products 1 (DOP1) of the Center for Drug Evaluation and Research (CDER) of the U.S. Food and Drug Administration ("FDA") has been submitted (Press release, Panther Biotechnology, OCT 10, 2016, View Source [SID1234517403]). The purpose of the requested meeting is to obtain FDA’s input regarding Panther’s plans for the development of TRF-DOX, Panther’s novel transferrin-doxorubicin conjugate for the treatment of platinum-resistant ovarian cancer. In preparation for the meeting, Panther is preparing a Pre-IND Package to be submitted to FDA that describes the information Panther intends on submitting in the TRF-DOX IND planned for submission in 2017. The IND is the regulatory vehicle that will allow for the initiation of clinical trials with TRF-DOX for the treatment of ovarian cancer.

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FDA will specifically review Panther’s manufacturing, preclinical pharmacology and toxicology, and clinical plans for TRF-DOX and provide specific feedback to Panther prior to the meeting.

TRF-DOX binds to transferrin receptors on tumor cells, inhibits cancer cell proliferation and causes cell death. TRF-DOX has been shown to exhibit increased cytotoxicity relative to unconjugated doxorubicin toward a variety of cancer cell lines and reduced cytotoxicity to normal cells. In addition to improvements in cytotoxicity and selectivity, TRF-DOX exhibits cytotoxic effects in many multidrug-resistant cells in vitro. Tumor targeting of doxorubicin to transferrin receptors on the cell membranes of tumor cells is intended to improve the therapeutic index of doxorubicin and to reduce the development of doxorubicin resistance. Panther is proposing to conduct an open label, multiple ascending dose study to investigate the safety, pharmacokinetics and preliminary efficacy of TRF-DOX in patients with platinum-resistant ovarian cancer.

On October 10, 2016 NOXXON Pharma N.V. (Paris:ALNOX) a clinical-stage biopharmaceutical company primarily focused on cancer treatment, reported that it presented data yesterday at the ESMO (Free ESMO Whitepaper) conference in Copenhagen, Denmark, studying the role of CXCL12 inhibition by NOX-A12 (olaptesed pegol) in tumor stroma spheroids, a preclinical model that mimics the complexity of the tumor microenvironment (Press release, NOXXON, OCT 10, 2016, View Source [SID:SID1234515721]). These studies showed that NOX-A12 synergizes with therapies working through either T cells or NK cells. Further studies of NOX-A12 with agents working through T-cells such as checkpoint inhibitors or CAR-T cells as well as NK cell-based therapies are warranted.

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Poster Title: CXCL12 Inhibition with NOX-A12 (Olaptesed Pegol) Increases T and NK Cell Infiltration and Synergizes with Immune Checkpoint Blockade and ADCC in Tumour-Stroma Spheroids
Authors: Dirk Zboralski, Anna Kruschinski, Dirk Eulberg and Axel Vater
Location & time: ESMO (Free ESMO Whitepaper) Congress 2016, Copenhagen, Denmark, 7-11 October 2016, Session Immunotherapy of cancer: Abstract #1083P, Hall E, Sunday, 9 October 2016, 13:00 – 14:00

The poster may be downloaded from the company’s website:
www.noxxon.com/downloads/poster/ESMO2016.pdf

NOX-A12, which inhibits the key tumor microenvironment chemokine CXCL12, may be a key partner for a wide range of IO (immuno-oncology) agents. NOXXON has generated promising pre-clinical and clinical data, including recent animal data showing synergy with a checkpoint inhibitor as well as recent phase 2a trials in multiple myeloma and a second hematological cancer that showed a safety profile that supports further development and first signs of efficacy. The company believes that additional clinical trials are warranted to investigate combinations of NOX-A12 multiple classes of IO agents including those acting on or through T-cells and NK cells.

On October 10, 2016 Genomic Health, Inc. (Nasdaq: GHDX) reported results from eight Oncotype DX Breast Recurrence Score (RS) presentations at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress in Copenhagen, Denmark, highlighting superior clinical evidence in identifying which patients with node-negative and node-positive invasive breast cancer should be treated with chemotherapy (Press release, Genomic Health, OCT 10, 2016, View Source [SID:SID1234515720]). Specifically, prospective clinical outcomes in more than 7,400 patients with node-positive invasive breast cancer from two independent studies show excellent survival in women with RS results less than 18.

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"The ESMO (Free ESMO Whitepaper) presentations continue to reinforce that Oncotype DX provides unique and unsurpassed value beyond tumor size and tumor grade for invasive breast cancer patients with node-negative and certain patients with node-positive disease," said Steven Shak, M.D., chief scientific officer, Genomic Health. "With our level 1 evidence for predicting chemotherapy benefit and prospective outcomes now in over 63,000 patients from the TAILORx, Clalit, PlanB and SEER studies, it is clear that Oncotype DX is the only genomic test that can provide doctors with confidence that their patients will receive the quality care they deserve."

New data confirm Oncotype DX accurately predicts clinical outcomes in node-positive breast cancer patients
Two independent studies in more than 7,400 patients from the United States and Israel provide further evidence that Oncotype DX accurately predicts outcomes in patients with early-stage, node-positive invasive breast cancer. Specifically, an updated analysis of the National Cancer Institute’s (NCI) Surveillance, Epidemiology, and End Results (SEER) Registry results from 6,768 patients who were treated based on RS results showed that in 3,919 patients with a RS of less than 18, breast cancer specific survival was excellent. Specifically, it was greater than 97 percent in patients with micrometastases, one, or two positive lymph nodes.

Similarly, results from a prospective study of more than 700 patients tested with Oncotype DX within Clalit Health Services, the largest health maintenance organization in Israel, showed that patients with micrometastases or one to three positive lymph nodes and a RS less than 18, the vast majority (92.9 percent) of whom were treated with hormonal therapy alone, had very good outcomes with low rates of distant recurrence (3.2 percent) and excellent breast cancer survival ( > 99 percent) at five years.

"These two important updates add significantly to the growing body of evidence that Oncotype DX accurately predicts outcomes and aids treatment decision making in women with early-stage, node-positive breast cancer. Just as we have learned in node-negative disease, it is now increasingly evident that women with one to three positive nodes and the lower scores do extremely well without chemotherapy," said Kathy S. Albain, MD, FACP, FASCO, professor of medicine, Loyola University Chicago, Cardinal Bernardin Cancer Center, Maywood, IL. "While we are now completing accrual of the RxPONDER trial looking at whether chemotherapy adds to standard endocrine therapy in this group, getting the results will take several years. In the meantime, these data along with previously published results, provide extremely strong evidence to justify use of Oncotype DX in 1-3 node-positive disease. If the patient’s tumor biology is that of a low Recurrence Score, chemotherapy simply does not add benefit, and its risks and costs can be avoided."

In addition, exploratory analyses of patients with RS results of 18 to 30 showed that the rate of distant recurrence were generally closer to lower risk patients with a RS less than 18. The group of patients with mid-range Recurrence Score results is also being studied in the Trial Assigning IndividuaLized Options for Treatment (Rx), or TAILORx, and the RxPONDER trial.

Oral presentation of additional SEER analysis reveals large disparities in survival and Oncotype DX testing in older patients
Following up on the results of the multinational TEAM study, which reported worse outcomes for older patients with hormone-receptor-positive (HR+) breast cancer, this study examined RS results in patients 70 years and older versus those under 70 years. The results showed that mortality was indeed much higher in older patients who were either not tested with Oncotype DX or had a RS result greater than 18. Patients age 70 or older also had lower reported chemotherapy use, supporting continued examination of the often reported issue of under-treatment of the elderly.

Oncotype DX reduces overtreatment of breast cancer and increases confidence in treatment decisions globally
Results from multiple international studies conducted in Canada, the Czech Republic, Italy and Spain reinforce the findings of more than 20 previous decision impact studies from around the world. Collectively, the results demonstrated that the RS increases confidence in treatment decisions and changes approximately 30 percent of treatment recommendations, resulting in a 22-24 percent reduction in use of chemotherapy in patients, including in those with node-positive disease.

About Oncotype DX
The Oncotype DX portfolio of breast, colon and prostate cancer tests applies advanced genomic science to reveal the unique biology of a tumor in order to optimize cancer treatment decisions. With more than 600,000 patients tested in more than 90 countries, the Oncotype DX tests have redefined personalized medicine by making genomics a critical part of cancer diagnosis and treatment. To learn more about Oncotype DX tests, visit www.OncotypeDX.com, www.mybreastcancertreatment.org and www.myprostatecancertreatment.org.

On October 10, 2016 Galena Biopharma, Inc. (NASDAQ:GALE), a biopharmaceutical company committed to the development and commercialization of hematology and oncology therapeutics that address unmet medical needs, reported that it has presented interim safety data from the Company’s NeuVax (nelipepimut-S) Phase 2b combination study with trastuzumab at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress in Copenhagen, Denmark (Press release, Galena Biopharma, OCT 10, 2016, View Source [SID:SID1234515719]). The clinical trial is a randomized, multicenter, investigator-sponsored, 300 patient Phase 2b study. It is currently enrolling HER2 1+ and 2+ node positive, and high-risk node negative patients to study NeuVax in combination with trastuzumab to prevent breast cancer recurrence.

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Poster #1069P, entitled "Interim safety analysis of a phase II trial combining trastuzumab and NeuVax, a HER2-targeted peptide vaccine, to prevent breast cancer recurrence in HER2 low expression," demonstrated that this novel combination of trastuzumab and NeuVax in HER2 low-expressing (LE) patients is well-tolerated and the cardiac effects of trastuzumab are not impacted by the addition of NeuVax.

In March 2016, the 150th patient was randomized into the trial, triggering this pre-specified safety analysis (Vaccine Group (VG) n=81, Control Group (CG) n=69). There were no significant differences in treatment factors, but a significant difference in node positivity appreciated between the groups. The sponsor expects this randomization imbalance to equalize over the duration of the study. Cardiac ejection fraction (EF) was assessed at baseline and serially throughout treatment. The majority of toxicities were Grade 1 and 2, and there was no difference between treatment arms. There was no difference in EF over time (baseline (T0) to 6mo (T6)) between VG v CG (T0: 61.4+0.6%, T6: 60.5+0.9% v T0: 61.6+0.7%, T6: 60.7+1.0%, p=0.9). There was one CG patient who experienced a grade 3 cardiac adverse event, but their EF returned to baseline after discontinuation of trastuzumab.

"This pre-specified, interim safety analysis is crucial to this trial to ensure that the combination of NeuVax and trastuzumab is well-tolerated in patients, and importantly that it does not increase the cardio-toxicity effects known to be associated with trastuzumab," said Bijan Nejadnik, M.D., Executive Vice President and Chief Medical Officer. "There is a growing consensus that combination therapies may yield the greatest clinical benefit, and this Phase 2b trial remains ongoing with enrollment expected to complete by the end of this year. As a result, we expect to report our first interim efficacy and immunologic outcomes after 12 months of follow-up, currently expected at the end of 2017. We are grateful to Dr. George Peoples and his team who continue this groundbreaking work."

Disease-free, HLA-A2+, A3+, A24+, or A26+, HER2 LE breast cancer patients at high risk for recurrence were enrolled after standard of care treatment and randomized to vaccine group (VG) receiving trastuzumab and NeuVax or control group (CG) receiving trastuzumab and GM-CSF only. Trastuzumab dosing was 8mg/kg loading, then 6mg/kg every 3 weeks. Patients received 6 total inoculations of NeuVax or GM-CSF, one every 3 weeks starting with the third trastuzumab infusion, followed by four booster inoculations administered every 6 months. Demographic and safety data were collected and analyzed with appropriate statistical tests.

The poster presentation from the conference will be available on Galena’s website here.
Abstract #3981 can be found on the conference website here.

About NeuVax (nelipepimut-S)

NeuVax (nelipepimut-S) is a first-in-class, HER2-directed cancer immunotherapy under evaluation to prevent breast cancer recurrence after standard of care treatment in the adjuvant setting. It is the immunodominant peptide derived from the extracellular domain of the HER2 protein, a well-established target for therapeutic intervention in breast carcinoma. The nelipepimut-S sequence stimulates specific CD8+ cytotoxic T lymphocytes (CTLs) following binding to specific HLA molecules on antigen presenting cells (APC). These activated specific CTLs recognize, neutralize and destroy, through cell lysis, HER2 expressing cancer cells, including occult cancer cells and micrometastatic foci. The nelipepimut-S immune response can also generate CTLs to other immunogenic peptides through inter- and intra-antigenic epitope spreading. In clinical studies, NeuVax is combined with recombinant granulocyte macrophage-colony stimulating factor (GM-CSF).

NeuVax is currently in two breast cancer studies in combination with trastuzumab (Herceptin; Genentech/Roche): a Phase 2b trial in node positive and triple negative HER2 IHC 1+/2+ (clinicaltrials.gov identifier: NCT01570036); and, a Phase 2 trial in high risk, node positive or negative HER2 IHC 3+ patients (clinicaltrials.gov identifier: NCT02297698). Phase 2 clinical trials with NeuVax are also planned in patients with ductal carcinoma in situ (DCIS), and in patients with gastric cancer.

About HER2 1+/2+ Breast Cancer

According to the National Cancer Institute, over 230,000 women in the U.S. are diagnosed with breast cancer annually. Of these women, only about 25% are HER2 positive (IHC 3+). NeuVax targets approximately 50%-60% of these women who are HER2 low to intermediate (IHC 1+/2+ or FISH < 2.0) and achieve remission with current standard of care, but have no available HER2-targeted adjuvant treatment options to maintain their disease-free status.