On December 14, 2016 Pfizer Inc. (NYSE:PFE) and Astellas Pharma Inc. (TSE:4503) reported the Phase 4 PLATO study, evaluating the efficacy and safety of continued treatment with XTANDI (enzalutamide), plus abiraterone acetate and prednisone as compared to treatment with abiraterone acetate and prednisone alone, did not meet its primary endpoint of improvement in progression-free survival (PFS) in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (CRPC) whose prostate-specific antigen (PSA) has previously progressed on XTANDI (Press release, Pfizer, DEC 14, 2016, View Source [SID1234517076]).

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"While the PLATO trial did not meet its primary endpoint, it is critical that we continue to focus on addressing the unmet needs of men with metastatic CRPC, who have a poor prognosis despite treatment advances," said Mohammad Hirmand, M.D., interim chief medical officer at Medivation, Inc., which is now part of Pfizer. "We will continue to analyze these data to better understand the results with the goal of further helping these patients."

understand the results with the goal of further helping these patients."

"XTANDI continues to remain an important treatment option for men with metastatic CRPC and their physicians. We are committed to continuing to explore the clinical potential of XTANDI across the disease continuum," said Steven Benner, M.D., senior vice president, therapeutic area head for oncology development, Astellas.

XTANDI is approved by the U.S. Food and Drug Administration for the treatment of patients with metastatic castrate-resistant prostate cancer (CRPC), based on clinical studies showing statistically significant overall survival benefit versus placebo.

About PLATO

The Phase 4 PLATO trial (NCT01995513) is a global randomized, double-blind, placebo-controlled, two-period study designed to evaluate the efficacy and safety of continued treatment with XTANDI plus abiraterone acetate and prednisone at the time of confirmed PSA progression, as compared to treatment with abiraterone acetate and prednisone alone at the time of PSA progression. The study enrolled 509 patients with chemotherapy-naïve metastatic CRPC who received open label XTANDI during period 1 of the study, until PSA progression was confirmed. Eligible patients were then randomized to one of the two treatments and assessed for the primary endpoint of the study, PFS, defined by either: 1) radiographic progression or 2) unequivocal clinical progression or 3) death during the study.

Period 1 patients were treated with XTANDI 160mg/day orally and period 2 patients were treated with blinded XTANDI 160 mg/day orally in combination with abiraterone at a dose of 1,000 mg/day administered orally and prednisone at a dose of 5 mg administered orally twice daily, versus placebo plus the same doses of abiraterone acetate and prednisone.

For additional information regarding the PLATO trial, visit clinicaltrials.gov (link is external).

About Metastatic Castration-Resistant Prostate Cancer (CRPC)

Metastatic castration-resistant prostate cancer (CRPC) refers to prostate cancer that has spread to parts of the body other than the prostate, and continues to spread despite treatment.1 Up to 40 percent of men diagnosed with prostate cancer who undergo therapy develop metastatic, or advanced, prostate cancer.2 In the U.S., the five-year relative survival rate for prostate cancer patients with metastatic disease is 28 percent, compared with 100 percent for prostate cancer patients with non-metastatic disease.3

About XTANDI (enzalutamide) capsules

XTANDI (enzalutamide) is an androgen receptor inhibitor that blocks multiple steps in the androgen receptor signaling pathway within the tumor cell. In preclinical studies, enzalutamide has been shown to competitively inhibit androgen binding to androgen receptors, and inhibit androgen receptor nuclear translocation and interaction with DNA. The clinical significance of this mechanism of action (MOA) is unknown.

XTANDI is approved by the U.S. Food and Drug Administration for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).

Important Safety Information

Contraindications

XTANDI is not indicated for women. XTANDI can cause fetal harm and potential loss of pregnancy.

Warnings and Precautions

Seizure occurred in 0.5% of patients receiving XTANDI in clinical studies. In placebo-controlled studies, 8 of 1671 (0.5%) patients treated with XTANDI and 1 of 1243 (0.1%) patients treated with placebo experienced a seizure. In patients who previously received docetaxel, 7 of 800 (0.9%) patients treated with XTANDI experienced a seizure and no patients treated with placebo experienced a seizure. In a placebo-controlled study in chemotherapy-naïve patients, 1 of 871 (0.1%) treated with XTANDI and 1 of 844 (0.1%) patients treated with placebo experienced a seizure. In bicalutamide-controlled studies conducted in chemotherapy-naïve patients, 3 of 380 (0.8%) patients treated with XTANDI and 1 of 387 (0.3%) patients treated with bicalutamide experienced a seizure. Permanently discontinue XTANDI in patients who develop a seizure during treatment.

Posterior Reversible Encephalopathy Syndrome (PRES) In post approval use, there have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder which can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES.

Adverse Reactions

The most common adverse reactions (≥ 10%) that occurred more commonly (≥ 2% over placebo) in the XTANDI patients from the two placebo-controlled clinical trials were asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight decreased, headache, hypertension, and dizziness/vertigo. In the bicalutamide-controlled study of chemotherapy naïve patients, the most common adverse reactions (≥ 10%) reported in XTANDI patients were asthenia/fatigue, back pain, musculoskeletal pain, hot flush, hypertension, nausea, constipation, upper respiratory tract infection, diarrhea, and weight loss.

In the study of patients taking XTANDI who previously received docetaxel, Grade 3 and higher adverse reactions were reported among 47% of XTANDI patients and 53% of placebo patients. Discontinuations due to adverse events were reported for 16% of XTANDI patients and 18% of placebo patients. In the placebo-controlled study of chemotherapy-naïve patients, Grade 3-4 adverse reactions were reported in 44% of XTANDI patients and 37% of placebo patients. Discontinuations due to adverse events were reported for 6% of both study groups. In the bicalutamide-controlled study of chemotherapy naïve patients, Grade 3-4 adverse reactions were reported in 38.8% of XTANDI patients and 37.6% of bicalutamide patients. Discontinuations due to adverse events were reported for 7.6% of XTANDI patients and 6.3% of bicalutamide patients.

Lab Abnormalities: In the two placebo-controlled trials Grade 1-4 neutropenia occurred in 15% of XTANDI patients (1% Grade 3-4) and 6% of placebo patients (0.5% Grade 3-4). Grade 1-4 thrombocytopenia occurred in 6% of XTANDI patients (0.3% Grade 3-4) and 5% of placebo patients (0.5% Grade 3-4). Grade 1-4 elevations in ALT occurred in 10% of XTANDI patients (0.2% Grade 3-4) and 16% of placebo patients (0.2% Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of XTANDI patients (0.1% Grade 3-4) and 2% of placebo patients (no Grade 3-4).

Infections: In a study of patients taking XTANDI who previously received docetaxel, 1% of XTANDI patients compared to 0.3% of placebo patients died from infections or sepsis. In the placebo-controlled study of chemotherapy-naïve patients, 1 patient in each treatment group (0.1%) had an infection resulting in death.

Falls (including fall-related injuries) occurred in 9% of XTANDI patients and 4% of placebo patients in the two placebo-controlled trials. Falls were not associated with loss of consciousness or seizure. Fall-related injuries were more severe in XTANDI patients, and included non-pathologic fractures, joint injuries, and hematomas.

Hypertension occurred in 11% of XTANDI patients and 4% of placebo patients in the two placebo-controlled trials. No patients experienced hypertensive crisis. Medical history of hypertension was balanced between arms. Hypertension led to study discontinuation in < 1% of all patients in each arm.

Drug Interactions

Effect of Other Drugs on XTANDI Avoid strong CYP2C8 inhibitors, as they can increase the plasma exposure to XTANDI. If co-administration is necessary, reduce the dose of XTANDI.

Avoid strong CYP3A4 inducers as they can decrease the plasma exposure to XTANDI. If co-administration is necessary, increase the dose of XTANDI.

Effect of XTANDI on Other Drugs Avoid CYP3A4, CYP2C9, and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.

Please see Full Prescribing Information at View Source (link is external) for additional safety information.

You are encouraged to report negative side effects of prescription drugs to the FDA.

Visit www.fda.gov/medwatch (link is external) or call 1-800-FDA-1088.

Champions Oncology has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission .

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On December 13, 2016 TTY Biopharm’s (4105:TW) reported that anticancer agent S-1 Capsule received a Taiwan National Health Insurance (NHI) reimbursement for adjuvant chemotherapy of locally-advanced gastric cancer [stage II (excluding T1), IIIA or IIIB in TNM system], after the review from Pharmaceutical Benefit and Reimbursement Scheme Joint committee (PBRS) (Press release, TTY Biopharm, DEC 13, 2016, View Source [SID1234527287]). The validated date was December 1st, 2016. This was the second reimbursement indication after S-1 Capsule had received its first reimbursement for locally advanced un-resectable or metastatic pancreatic cancer patient since June, 2014. S-1 Capsule had been developed by Taiho Pharmaceutical Co., Ltd. of Japan and TTY Biopharm received an exclusive right to develop and market in Taiwan.

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According to Ministry of Health and Welfare’s database, around 3,600 to 3,800 new patients were diagnosed with gastric cancer annually. Gastric cancer was ranked the 7th in cancer incidence and 5th in mortality. For the early stage gastric cancer, the primary treatment was surgery; however, about 40% of patients who were diagnosed with stage II and III gastric cancer after surgery would still relapse and nearly 90% of the relapsed cases happened within 3 years. Unfortunately, for those relapsed patients, the median survival rate was less than 10%. The clinical practice recommended chemotherapy to be an adjuvant therapy. S-1 Capsule, after publication of a large-scale randomized Phase III clinical trial, was approved to be the first agent to decrease the risk of death by 33.1% and risk of relapse by 34.7% for stage II (excluding T1)-III gastric cancer patients. It was also the only oral chemotherapy agent with TFDA and NHI reimbursement label in Stage II-IIIB gastric cancer. Clinical results were first published on the New England Journal of Medicine and the final result was published on Journal of Clinical Oncology.

TTY Biopharm indicated: "Although the number of patients with gastric cancer has slowed down, the overall survival rate is lower than other Asian countries, Japan and South Korea for example. We keep not only reminding citizens to receive regular upper gastrointestinal examinations, but also educating public the benefits of adjuvant chemotherapy for lowering the risk of relapse and increasing chances of being cured." S-1 Capsule is expected to allow patients to maintain original lives. With reimbursement for gastric cancer patients, about 1,200 patients would be benefitted.

On December 13, 2016 MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, as well as autoimmune disorders and infectious diseases, reported an update on several of the Company’s product candidates and technology platforms (Press release, MacroGenics, DEC 13, 2016, View Source [SID1234517060]).

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"At today’s R&D Day, MacroGenics highlighted the continued progress our team is making to advance our growing portfolio of potential treatment options for patients with cancer, autoimmune disorders and infectious diseases," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "Today, we reviewed our expanded strategy for pursuing a balanced approached across novel and validated targets to develop three immuno-oncology franchises centered around HER2, B7-H3 and PD-1. This approach underscores our belief that cancer patients may significantly benefit from combinatorial and multi-specific strategies that are directly addressed by our core scientific expertise in creating and developing antibody, DART and TRIDENT therapeutics. The promising updates we provided on 11 of our programs today underscore the potential of our approach."

Program Updates and Highlights:

HER2 Franchise. MacroGenics provided an update regarding its most advanced franchise targeting the human epidermal growth factor receptor 2, or HER2, led by margetuximab, its Fc-optimized monoclonal antibody:

Phase 3 Metastatic Breast Cancer Study. The pivotal SOPHIA study is evaluating the efficacy of margetuximab plus chemotherapy compared to trastuzumab plus chemotherapy in approximately 530 relapsed/refractory HER2-positive metastatic breast cancer patients. MacroGenics today confirmed that it expects to complete enrollment of this study by late 2018.
Phase 2 Gastric Cancer Combination of Margetuximab with Anti-PD-1 mAb. The Company presented initial clinical data from a Phase 1b/2 trial of margetuximab in combination with an anti-PD-1 monoclonal antibody (pembrolizumab) in advanced HER2-positive gastric and gastroesophageal junction cancer patients. Preliminary data from the dose escalation portion of the study includes patients with objective response following progression on previous lines of treatment with trastuzumab and chemotherapy.
Pre-Clinical DART Program. MacroGenics presented preliminary non-clinical data from a DART program designed to engage both HER2 and CD137 (4-1BB), a costimulatory molecule, allowing for tumor-targeted immune cell activation.
B7-H3 Franchise. MacroGenics highlighted its industry-leading franchise related to the therapeutic targeting of B7-H3, a member of the B7 family of molecules involved in immune regulation, that is broadly expressed in multiple solid tumors:

Enoblituzumab. The Company provided clinical updates on ongoing monotherapy and combination studies with enoblituzumab, an Fc-optimized monoclonal antibody. In the Phase 1 monotherapy study, the antibody continues to be well-tolerated and the most promising activity to-date has been observed in prostate, bladder and post-checkpoint melanoma patients, consistent with what has been previously reported. Combination studies of enoblituzumab with either an anti-CTLA-4 mAb (ipilimumab) or anti-PD-1 mAb (pembrolizumab) indicate a manageable safety profile to date as well as initial signs of antitumor activity.
MGD009. MacroGenics presented initial data from the ongoing Phase 1 dose escalation study of MGD009, a bispecific B7-H3 x CD3 DART molecule. Adverse events have been manageable to date and initial signs of antitumor activity have been observed in three patients with triple negative breast cancer, renal cell carcinoma and mesothelioma.
MGC018. The Company introduced MGC018, an anti-B7-H3 antibody drug conjugate (ADC) based on a duocarmycin payload with cleavable peptide linker licensed from Synthon Biopharmaceuticals. The Company plans to submit an Investigational New Drug (IND) application for MGC018 in 2018.
PD1-Directed Immuno-Oncology Franchise. MacroGenics introduced several new programs in its pipeline directed towards PD-1, which will enable both a broad set of combination opportunities across its portfolio and further differentiation from existing PD-1-based treatment options:

MGA012. The Company introduced MGA012, an anti-PD-1 monoclonal antibody that recently began a Phase 1 clinical study. With anti-PD-1 therapy becoming a mainstay of cancer treatment across multiple tumors, MacroGenics believes this molecule will be the basis for combination therapy with several of its proprietary molecules.
MGD013. MacroGenics is developing MGD013 to provide co-blockade of two immune checkpoint molecules expressed on T cells, PD-1 and LAG-3, for potential treatment of diseases spanning a range of solid tumors as well as hematological malignancies. The Company has observed synergistic immunoregulatory activity in vitro, demonstrating that co-blockade with a PD-1 x LAG-3 DART molecule exceeds the effects achieved by combining two separate antibodies against these targets. The Company is completing IND-enabling studies and plans to submit an IND for MGD013 in the first half of 2017.
PD-1 x CTLA-4 Program. MacroGenics is developing a multi-specific therapeutic to address the co-blockade of PD-1 and CTLA-4, two clinically validated co-inhibitory molecules expressed on T cells.
Update on DART Clinical Programs. Across its portfolio of clinical DART programs, the Company highlighted the promising features of its DART platform, including on-target engagement, manageable safety and preliminary evidence of biological activity. These DART programs include MGD009 and the following:

MGD006. MacroGenics presented elements of its initial clinical experience from the ongoing Phase 1 dose escalation study of MGD006, a CD123 x CD3 DART molecule, in patients with AML (acute myeloid leukemia) or MDS (myelodysplastic syndrome). Supportive care regimens have been refined to enable significant limitations in the severity of cytokine release syndrome (CRS). In addition, the Company has characterized predictable pharmacokinetic properties of MGD006 and established biological and preliminary clinical activity in AML patients. The Company is now recruiting patients with AML or MDS in the U.S. and Europe.
MGD007. MacroGenics presented its initial clinical experience from the ongoing Phase 1 dose escalation study of MGD007, a gpA33 x CD3 DART, in patients with primary and metastatic colorectal cancers. In this study, gastrointestinal and constitutional symptoms have been reversible and consistent with the known target distribution of gpA33. Translational findings to date have included dose-dependent binding to CD4+ and CD8+ T cells in patients’ peripheral blood as well as histological demonstration of MGD007 binding to tumor cells in tumor biopsy specimens.

MGD010. The Company presented data from the fully enrolled Phase 1 study of MGD010, a CD32B x CD79B DART molecule, being developed for potential treatment of autoimmune disorders. MGD010 was well tolerated in healthy subjects in the single ascending dose study. In addition, MGD010 was shown to down-modulate B-cell function at multiple levels and preliminary data indicated that MGD010 was able to inhibit antibody response to Hepatitis A vaccination, providing clinical evidence consistent with the molecule’s expected mechanism of action.

On December Moleculin Biotech, Inc., (NASDAQ: MBRX) ("Moleculin" or the "Company"), a preclinical pharmaceutical company focused on the development of anti-cancer drug candidates, many of which are based on license agreements with The University of Texas System on behalf of the M.D. Anderson Cancer Center, reported its scientific presentation at the 28th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics (Press release, Moleculin, DEC 13, 2016, View Source [SID1234517062]). Waldemar Priebe, PhD, Moleculin’s Founder, Founding Scientist, and Chair of the Scientific Advisory Board presented the Abstract on November 30th at the Symposium in Munich, Germany.

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Wally Klemp, Chairman and CEO stated, "This presentation shows proof of concept data for our WP1122 portfolio, including data demonstrating increased survival of animals with human brain tumors treated with WP1122, as well as its biodistribution and pharmacokinetics. In non-optimal doses and treatment regimens, our lead inhibitor WP1122 performed equal to or better than the current market leader, cytotoxic drug temozolomide and significantly improved survival in animals treated with WP1122 in combination with temozolomide."

The following is an overview of the presentation, titled "Latentiation of 2-deoxy-D-glucose". No curative therapy exists for patients with high-grade malignant gliomas (GBMs). New approaches to the treatment of this disease are currently being evaluated with mixed results. One approach, that deserves to be therapeutically exploited, is targeting brain tumor metabolism. 2-Deoxy-D-glucose (2-DG), a known effective inhibitor of glycolysis, has been clinically tested but results did not meet expectations due to poor drug-like characteristics and inability to achieve therapeutic concentrations of 2-DG in the brain.

Dr. Waldemar Priebe stated, "We proposed to use latentiation of 2-DG to overcome this problem by chemically modifying biologically active 2-DG to form prodrugs with increased brain uptake that will be able to liberate in vivo the parent compound 2-DG in the brain. In our approach, we synthesized a series of differentially acetylated derivatives of 2-DG. Preliminary in vivo studies in mice of selected diacetates of 2-DG demonstrated >9 fold increased levels of 2-DG in the brain when compared with levels of 2-DG after administration of equimolar amount of 2-DG itself. Ultimately, our studies focused on a single compound 3,6-di-O-acetyl-2-deoxy-D-glucose (WP1122)."

Compound WP1122 was administered in vivo without toxic death up to the highest feasible dose of 3.0 g/kg intravenously and orally up to 6.0 g/kg. Significantly increased survival, comparable to or better than that of temozolomide, was observed for orally administered WP1122 in a U87 orthotopic glioma model at a dose of 1.25 g/kg. These promising results prompted continuation of preclinical toxicology evaluation of WP1122 aimed at the initiation of formal IND enabling studies. In addition, the proof of concept delivered by WP1122 has provided not only an effective approach to develop novel agents able to effectively cross the blood brain barrier but also a method to create a new class of dual function prodrugs by exploring biologically active acids.

Moleculin’s Chairman and CEO, Walter Klemp, concluded, "We are excited to present our results at this prestigious symposium. Clearly, the significantly increased survival data is key, especially as no curative therapy exists for patients with high-grade malignant gliomas today. We look forward to presenting additional data as we progress toward our clinical timeline."
For more information on the Symposium click: View Source