On September 18, 2015 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on the development and commercialization of new cancer immunotherapies, reported the presentation of clinical and preclinical data from the Company’s Ad-RTS-IL-12 program in various malignancies at the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) taking place September 16-19, 2015 in New York City (Press release, Ziopharm, SEP 18, 2015, View Source [SID:1234507506]). Ad-RTS-IL-12 is a novel gene therapy candidate for the controlled expression of IL-12, a critical protein for stimulating an anti-cancer T cell immune response.

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The first poster presentation, titled, "Demonstration of Systemic Antitumor Immunity via Intratumoral Regulated Expression of IL-12 in Advanced Breast Cancer and Melanoma Patients," highlights additional evidence of systemic immune activation with AD-RTS-hIL-12 and veledimex in advanced melanoma and breast cancer patients. The data were drawn from two previously completed open-label Phase II clinical studies: one which enrolled 12 patients with metastatic advanced stage breast cancer, and one which enrolled 26 patients with metastatic melanoma, both exploring the immune-mediated local and systemic anti-tumor effects of Ad-RTS-hIL-12 and veledimex. Among other findings, treatment with Ad-RTS-hIL-12 and veledimex in patients with melanoma was found to increase in the immune cytokine IL-12 and downstream cytokines, IFNg, IP-10 and IL-10, resulting in a significant increase in tumor infiltrating lymphocytes both locally, in injected lesions, and systemically, in non-injected lesions.

The second poster presentation, titled "Demonstration of Systemic Antitumor Immunity via Intratumoral Regulated Expression of IL-12 as a Gene Therapy Approach to Treatment of Cancer," demonstrates the anti-tumor effects and tolerability of Ad-RTS-mIL-12 in murine models of glioblastoma (brain cancer), colon cancer and melanoma. The data demonstrated dose-related increases in veledimex in both plasma and brain tissue, leading to an increase in expression of IL-12 mRNA and in-tumor IL-12p70 expression with minimal increase in serum IL-12. Ad-RTS-mIL-12 + veledimex also demonstrated systemic memory upon rechallenge in multiple syngeneic mouse models, providing further evidence of systemic anti-tumor immunity elicited by Ad-RTS-mIL-12.

Both posters are available under "Presentations and Publications" on the Company’s website at www.ziopharm.com. In addition to the poster presentations, Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM, is scheduled to deliver an oral presentation titled "Non-viral gene transfer to redirect T cell specificity" on Saturday, September 19.

"Clinical and preclinical data from our Ad-RTS-IL-12 program continue to demonstrate the ability to achieve both local anti-tumor effect and systemic effects across a variety of malignancies," said Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM. "We look forward to understanding how these results translate to our ongoing, multicenter Phase 1 gene therapy study in malignant glioma as well as our Phase 1b/2 Study in locally advanced or metastatic breast cancer. These data also provide support for our integration of both the RTS gene switch and cytokines into our broader adoptive cell therapy programs."

On September 18, 2015 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing novel protein therapeutics for cancer and inflammatory diseases, reported that the Phase 1a/1b clinical trial combining FPA008 with OPDIVO (nivolumab) in multiple tumor types was featured today in a trial-in-progress poster at the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) in New York City (Press release, Five Prime Therapeutics, SEP 18, 2015, View Source [SID:1234507502]). FPA008 is Five Prime’s monoclonal antibody that inhibits colony stimulating factor-1 receptor (CSF1R). OPDIVO is Bristol-Myers Squibb’s PD-1 immune checkpoint inhibitor. The poster entitled "A Phase 1a/1b Study of FPA008 in Combination with Nivolumab in Patients with Selected Advanced Cancers" was presented by F. Stephen Hodi, Jr., M.D., of Dana-Farber Cancer Institute.

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The comprehensive design of the study, which is being conducted by Five Prime under a clinical collaboration with Bristol-Myers Squibb, will allow the company to explore the potential of FPA008 in immuno-oncology, both as a monotherapy and in combination with anti-PD-1 therapy. During Phase 1a, Five Prime will evaluate the safety, pharmacokinetics and biomarkers of escalating doses of FPA008 alone, and in combination with the approved 3 mg/kg dose of nivolumab. Approximately 30 patients with advanced cancers are expected to be enrolled during Phase 1a and both drugs will be administered every two weeks. In Phase 1b, Five Prime will evaluate the safety, tolerability and preliminary efficacy of the selected dose of FPA008 in combination with nivolumab in approximately 240 patients across eight tumor settings:

Second- or third-line non-small cell lung cancer (NSCLC, anti PD-1 therapy naïve)
Anti PD-1 therapy resistant NSCLC (either de novo or acquired)
Previously untreated melanoma (anti PD1 therapy naïve)
Anti PD-1 therapy resistant melanoma (de novo)
Second-line squamous cell carcinoma of the head and neck
Second-line pancreatic cancer
Third-line colorectal cancer
Second-line glioblastoma multiforme (GBM)

Tumor biopsies will be obtained both pre-treatment and one month post-treatment in all patients enrolled in the Phase 1a portion and in a subset of patients enrolled in the Phase 1b portion to analyze the immune response within the tumor microenvironment. Five Prime will use this analysis to further guide FPA008’s development in oncology.

"We are pleased to now have patient dosing underway and to be evaluating the FPA008/nivolumab immunotherapy combination in the original six tumor settings we’ve communicated, as well as in two additional settings, anti-PD1 resistant non-small cell lung cancer and melanoma," said Julie Hambleton, M.D., Executive Vice President and Chief Medical Officer of Five Prime. "We remain on track to complete Phase 1a dose escalation and expand into Phase 1b across the eight tumor settings in late 2015 or early 2016."

About FPA008

FPA008, Five Prime’s antibody that inhibits colony stimulating factor-1 receptor (CSF1R), targets macrophages and monocytes, which are activated or elevated in multiple disease settings. In cancer, tumor-associated macrophages suppress the immune system’s ability to kill cancer cells. In joint diseases, such as PVNS and RA, synovial macrophages play a central role in the disease process. Five Prime is evaluating the immunotherapy combination of FPA008 and OPDIVO (nivolumab), Bristol-Myers Squibb’s investigational PD-1 immune checkpoint inhibitor, in six tumor types in a Phase 1a/1b clinical trial. Five Prime is also conducting a Phase 1/2 trial of FPA008 in pigmented villonodular synovitis (PVNS), a joint tumor driven by the CSF1 pathway and an orphan disease, and a Phase 1 study in rheumatoid arthritis.

On September 18, 2015 Amgen (NASDAQ: AMGN) reported the U.S. Food and Drug Administration (FDA) has accepted for priority review the supplemental New Drug Application (sNDA) of Kyprolis (carfilzomib) for Injection for patients with relapsed multiple myeloma (Press release, Amgen, SEP 18, 2015, View Source;p=RssLanding&cat=news&id=2088926 [SID:1234507501]). The sNDA is designed to expand the current indication to include Kyprolis in combination with dexamethasone for patients who have received at least one prior therapy. The Prescription Drug User Fee Act (PDUFA) target action date is Jan. 22, 2016.

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The FDA’s acceptance of this new sNDA for Kyprolis follows the recent FDA approval for Kyprolis in combination with Revlimid (lenalidomide) and dexamethasone for the treatment of patients with relapsed multiple myeloma who have received one to three prior lines of therapy.

Multiple myeloma is a rare and complex blood cancer that has historically been one of the most difficult to treat diseases because of the inherent complexities related to the recurring pattern of remission and relapse. Patients face poor outcomes, which worsen with each relapse.

"Clinicians need a range of options and robust clinical data to make informed choices that can ideally extend the time patients live without their cancer progressing," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "The acceptance of this submission is an important next step toward providing more options for patients with relapsed multiple myeloma and we look forward to working with the FDA over the coming months."

The application is based on data from the Phase 3 head-to-head ENDEAVOR study, which showed that patients with relapsed multiple myeloma treated with Kyprolis and low-dose dexamethasone lived twice as long without their disease worsening, demonstrating statistically and clinically significant superiority over bortezomib and low-dose dexamethasone (median progression-free survival [PFS] 18.7 months versus 9.4 months, HR=0.53, 95 percent CI, 0.44 – 0.65; p<0.0001).

Treatment discontinuation due to adverse events and on-study deaths was comparable between the two arms. The rates of cardiac failure and renal failure for Kyprolis were comparable to those observed in the Phase 3 ASPIRE study. In ENDEAVOR, the rates for cardiac and renal failure were higher in the Kyprolis arm versus the bortezomib arm. There was also an increase in the incidence of hypertension and dyspnea in the Kyprolis arm compared to bortezomib in ENDEAVOR.

Priority review is assigned to applications for drugs that treat serious conditions and would, if approved, provide significant improvements in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions.

About ENDEAVOR

The randomized ENDEAVOR (RandomizEd, OpeN Label, Phase 3 Study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma) trial of 929 patients evaluated Kyprolis in combination with low-dose dexamethasone, versus bortezomib with low-dose dexamethasone in patients whose multiple myeloma has relapsed after at least one, but not more than three prior therapeutic regimens. The primary endpoint of the trial was PFS, defined as the time from treatment initiation to disease progression or death.

Patients received Kyprolis as a 30-minute infusion on two consecutive days, each week for three weeks followed by a 12 day rest period. Kyprolis was administered on days 1, 2, 8, 9, 15 and 16 of 28 day treatment cycles, along with low-dose dexamethasone (20 mg). For Cycle 1 only, Kyprolis was administered at 20 mg/m2 on days 1 and 2, followed by escalation to 56 mg/m2 from day 8. Patients who tolerated 56 mg/m2 in Cycle 1 were kept at this dose for subsequent cycles. Patients who received bortezomib (1.3 mg/m2) with low-dose dexamethasone (20 mg) were administered bortezomib subcutaneously or intravenously at the discretion of the investigator and in accordance with regulatory approval of bortezomib. More than 75 percent of the patients in the control arm received bortezomib subcutaneously. This study was conducted at 235 sites worldwide. For information about this trial, please visit www.clinicaltrials.gov under trial identification number NCT01568866.

About Multiple Myeloma

Multiple myeloma is the second most common hematologic cancer and results from an abnormality of plasma cells, usually in the bone marrow.1,2 Worldwide, nearly 230,000 people are living with multiple myeloma and approximately 114,000 new cases are diagnosed annually.3 In the U.S., there are nearly 96,000 people living with, or in remission from, multiple myeloma. The estimated number of new cases of multiple myeloma in 2014 was more than 24,000 in the U.S. and the estimated number of deaths was 11,090.4 In Europe, approximately 89,000 people are living with the disease and in 2012 there was an estimated 39,000 newly diagnosed cases and 24,000 deaths.3

About Kyprolis (carfilzomib) for Injection

Kyprolis (carfilzomib) for Injection received approval from the U.S. FDA in July 2015 for combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior lines of therapy.

Kyprolis is also indicated under FDA accelerated approval in July 2012 as a single agent for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an immunomodulatory agent and have demonstrated disease progression on or within 60 days of completion of the last therapy. Approval is based on response rate. Clinical benefit, such as improvement in survival or symptoms, has not been verified.

Kyprolis is a product of Onyx Pharmaceuticals, Inc. Onyx Pharmaceuticals is a subsidiary of Amgen and holds development and commercialization rights to Kyprolis globally, excluding Japan. Kyprolis is also approved for use in Argentina, Israel, Kuwait, Mexico and Thailand. For more information about Kyprolis, visit www.kyprolis.com.

Important Safety Information Regarding Kyprolis (carfilzomib) for Injection

Cardiac Toxicities

New onset or worsening of pre-existing cardiac failure (e.g., congestive heart failure, pulmonary edema, decreased ejection fraction), restrictive cardiomyopathy, myocardial ischemia, and myocardial infarction including fatalities have occurred following administration of Kyprolis. Death due to cardiac arrest has occurred within a day of Kyprolis administration.

Withhold Kyprolis for Grade 3 or 4 cardiac adverse events until recovery, and consider whether to restart Kyprolis based on a benefit/risk assessment.

Adequate hydration is required prior to each dose in Cycle 1. Monitor all patients for evidence of volume overload, especially patients at risk for cardiac failure. Adjust total fluid intake as clinically appropriate in patients with baseline cardiac failure or who are at risk for cardiac failure.

Patients > 75 years, the risk of cardiac failure is increased. Patients with New York Heart Association Class III and IV heart failure, recent myocardial infarction, and conduction abnormalities may be at greater risk for cardiac complications.

Acute Renal Failure

Cases of acute renal failure and renal insufficiency adverse events (renal impairment, acute renal failure, renal failure) have occurred in patients receiving Kyprolis. Acute renal failure was reported more frequently in patients with advanced relapsed and refractory multiple myeloma who received Kyprolis monotherapy. This risk was greater in patients with a baseline reduced estimated creatinine clearance. Monitor renal function with regular measurement of the serum creatinine and/or estimated creatinine clearance. Reduce or withhold dose as appropriate.

Tumor Lysis Syndrome

Cases of Tumor Lysis Syndrome (TLS), including fatal outcomes, have occurred in patients receiving Kyprolis. Patients with multiple myeloma and a high tumor burden should be considered at greater risk for TLS. Adequate hydration is required prior to each dose in Cycle 1, and in subsequent cycles as needed. Consider uric acid lowering drugs in patients at risk for TLS. Monitor for evidence of TLS during treatment and manage promptly. Withhold Kyprolis until TLS is resolved.

Pulmonary Toxicity

Acute Respiratory Distress Syndrome (ARDS), acute respiratory failure, and acute diffuse infiltrative pulmonary disease such as pneumonitis and interstitial lung disease have occurred in patients receiving Kyprolis. Some events have been fatal. In the event of drug-induced pulmonary toxicity, discontinue Kyprolis.

Pulmonary Hypertension

Pulmonary arterial hypertension (PAH) was reported in patients treated with Kyprolis. Evaluate with cardiac imaging and/or other tests as indicated. Withhold Kyprolis for PAH until resolved or returned to baseline and consider whether to restart Kyprolis based on a benefit/risk assessment.

Dyspnea

Dyspnea was reported in patients treated with Kyprolis. Evaluate dyspnea to exclude cardiopulmonary conditions including cardiac failure and pulmonary syndromes. Stop Kyprolis for Grade 3 or 4 dyspnea until resolved or returned to baseline. Consider whether to restart Kyprolis based on a benefit/risk assessment.

Hypertension

Hypertension, including hypertensive crisis and hypertensive emergency, has been observed with Kyprolis. Some of these events have been fatal. Monitor blood pressure regularly in all patients. If hypertension cannot be adequately controlled, withhold Kyprolis and evaluate. Consider whether to restart Kyprolis based on a benefit/risk assessment.

Venous Thrombosis

Venous thromboembolic events (including deep venous thrombosis and pulmonary embolism) have been observed with Kyprolis. Thromboprophylaxis is recommended and should be based on an assessment of the patient’s underlying risks, treatment regimen, and clinical status.

Infusion Reactions

Infusion reactions, including life-threatening reactions, have occurred in patients receiving Kyprolis. Symptoms include fever, chills, arthralgia, myalgia, facial flushing, facial edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina. These reactions can occur immediately following or up to 24 hours after administration of Kyprolis. Premedicate with dexamethasone to reduce the incidence and severity of infusion reactions. Inform patients of the risk and of symptoms of an infusion reaction and to contact a physician immediately if they occur.

Thrombocytopenia

Kyprolis causes thrombocytopenia with recovery to baseline platelet count usually by the start of the next cycle. Thrombocytopenia was reported in patients receiving Kyprolis. Monitor platelet counts frequently during treatment with Kyprolis. Reduce or withhold dose as appropriate.

Hepatic Toxicity and Hepatic Failure

Cases of hepatic failure, including fatal cases, have been reported during treatment with Kyprolis. Kyprolis can cause increased serum transaminases. Monitor liver enzymes regularly. Reduce or withhold dose as appropriate.

Thrombotic Thrombocytopenic Purpura /Hemolytic Uremic Syndrome (TTP/HUS)

Cases of TTP/HUS including fatal outcome have occurred in patients receiving Kyprolis. Monitor for signs and symptoms of TTP/HUS. Discontinue Kyprolis if diagnosis is suspected. If the diagnosis of TTP/HUS is excluded, Kyprolis may be restarted. The safety of reinitiating Kyprolis therapy in patients previously experiencing TTP/HUS is not known.

Posterior Reversible Encephalopathy Syndrome (PRES)

Cases of PRES have occurred in patients receiving Kyprolis. PRES was formerly known as Reversible Posterior Leukoencephalopathy Syndrome. Consider a neuro-radiological imaging (MRI) for onset of visual or neurological symptoms. Discontinue Kyprolis if PRES is suspected and evaluate. The safety of reinitiating Kyprolis therapy in patients previously experiencing PRES is not known.

Embryo-fetal Toxicity

Kyprolis can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals.

Females of reproductive potential should be advised to avoid becoming pregnant while being treated with Kyprolis and the potential hazard to the fetus if Kyprolis is used during pregnancy.

ADVERSE REACTIONS

The most common adverse events occurring in at least 20% of patients treated with Kyprolis in monotherapy trials: anemia, fatigue, thrombocytopenia, nausea, pyrexia, decreased platelets, dyspnea, diarrhea, decreased lymphocyte, headache, decreased hemoglobin, cough, edema peripheral.

The most common adverse events occurring in at least 20% of patients treated with Kyprolis in the combination therapy trial: decreased lymphocytes, decreased absolute neutrophil count, decreased phosphorus, anemia, neutropenia, decreased total white blood cell count, decreased platelets, diarrhea, fatigue, thrombocytopenia, pyrexia, muscle spasm, cough, upper respiratory tract infection, decreased hemoglobin, hypokalemia.

Full prescribing information is available at www.kyprolis.com.

On September 18, 2015 The Bristol-Myers Squibb Foundation reported four new grants awarded through its landmark Secure the Future initiative that will strengthen community-based services addressing cervical cancer in Tanzania, where women living with HIV are more likely to die from cervical cancer than AIDS (Press release, Bristol-Myers Squibb, SEP 18, 2015, View Source [SID:1234507499]).

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The grants will support the ongoing work of four members of the Coalition for the Prevention of Cervical Cancer in Tanzania: Mbeya HIV/AIDS Network, Medical Women’s Association of Tanzania, Tanzania Marketing and Communications and Tanzania Youth Alliance. Secure the Future and the Tanzania coalition are collaborating with Pink Ribbon Red Ribbon to help communities in the East African country prevent cervical cancer by raising awareness and encouraging screening to improve early cervical cancer detection and treatment programs. Pink Ribbon Red Ribbon is affiliated with the George W. Bush Institute.

The Foundation has committed $1.2 million over three years to support Pink Ribbon Red Ribbon’s work in Tanzania and also supports similar work in Swaziland and Ethiopia.

"Cervical cancer is a leading cause of cancer death in women in sub-Saharan Africa," says John Damonti, president, Bristol-Myers Squibb Foundation. "Women in Tanzania are nearly three times more likely to suffer from cervical cancer than women living in other parts of the world. Tragically, four of every five women diagnosed with cervical cancer in Tanzania die within five years of their diagnosis because the cancer is detected at an advanced stage or because they have limited access to care."

The grants awarded by the Foundation directly address both of these problems by promoting awareness and early detection and by building health care system capacity in rural communities:

Mbeya HIV/AIDS Network will help raise community awareness about cervical and breast cancer screening, treatment and prevention services and build the capacity of community volunteers to address the needs of women living in the Chunya, Mbarali and Momba districts of Mbeya. Mbeya will leverage its existing infrastructure for HIV/AIDS, including prevention intervention and peer education, counseling and testing, and home-based care.

Medical Women’s Association of Tanzania will expand its cervical and breast cancer screening campaigns from eight regions to 12 – adding Mwanza, Mara, Mbeya and Iringa – and build the capacity of health care providers while advocating for increased government support for cervical and breast cancer prevention and early detection services at the district, region and national levels.

Tanzania Youth Alliance (TAYOA) will use its national cervical cancer helpline, the government’s SMS short message services and a network of community leaders to help women in the Ilemela, Kwinba, Magu, Sengerema and Ukerewe districts in Mwanza connect with health centers, women’s groups and others who are working to prevent cervical cancer mortality. TAYAO also collaborates with Airtel Tanzania on media campaigns to raise awareness, inform and encourage community members to access to cancer screening services and early detection.

Tanzania Marketing and Communications (T-Marc) will expand its ongoing work with Secure the Future to promote public awareness about cervical cancer prevention, detection and treatment in Iringa to include 23 wards in the Kilolo district, 12 wards in the Mufindi district and 19 villages across Iringa. T-Marc will build capacity and strengthen three CBOs to advocate for, implement, and sustain cervical cancer community mobilization and demand creation interventions.