8-K – Current report

On September 23, 2015 Provectus Biopharmaceuticals, Inc. (NYSE MKT: PVCT, http://www.pvct.com), a development-stage oncology and dermatology biopharmaceutical company ("Provectus" or the "Company"), reported it has completed development of the protocol for Phase1b/2 testing of its investigational cancer drug PV-10 in combination with pembrolizumab in patients with Stage IV melanoma (Filing, 8-K, Provectus Pharmaceuticals, SEP 23, 2015, View Source [SID:1234507527]). Pembrolizumab (also known as Keytruda, a product of Merck and Co. Inc., NYSE: MRK) is an immune checkpoint inhibitor approved for treatment of patients with advanced or unresectable melanoma. PV-10 is Provectus’s novel investigational drug for cancer that is injected into solid tumors (intralesional administration); it is currently undergoing Phase 3 clinical testing in patients with Stage III melanoma. Clinical testing under the new Phase 1b/2 protocol is expected to commence before the end of the year.

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The combination protocol enables initial clinical testing of concepts at the center of a patent held by Provectus, U.S. Patent number 9,107,887, which Pfizer, Inc. (NYSE: PFE) jointly owns. Specifically, the patent covers the use of PV-10 in combination with systemic inhibitors of immune system down-regulation, such as anti-CTLA-4, PD-1 and PD-L1 immune checkpoint inhibiting antibodies. Pembrolizumab is an anti-PD-1 antibody. Pre-clinical testing of PV-10 used in combination with these important classes of drugs demonstrated potential importance for treatment of advanced cancers.

The FDA granted accelerated approval to pembrolizumab in September 2014, making it the first FDA-approved anti-PD-1 immune checkpoint inhibitor. Because pembrolizumab is already FDA-approved, Provectus can commence this study with or without assistance of a partner.

The Phase 1b/2 study will incorporate a modest sized single arm Phase 1b component of 24 subjects with expedited safety and efficacy end points. This is designed to support expansion to a larger randomized Phase 2 component. Combined, these two arms will enable assessment of the potential safety and clinical benefit of PV-10 when used with pembrolizumab for treatment of advanced melanoma.

Dr. Eric Wachter, CTO of Provectus, stated, "The primary end point of tolerability in the Phase 1b portion of the study, combined with assessment of progression free survival (PFS) and objective response rate (ORR) by RECIST criteria as key secondary endpoints, assessed over a 15 week treatment interval, establish a basis for determining whether to proceed to the larger, randomized Phase 2 portion of the study. We will use an adaptive design for powering Phase 2 based on preliminary results from Phase 1, and estimate this portion of the study to require at least 120 subjects, with a primary endpoint of PFS and key secondary endpoint of ORR. In both portions of the study, pembrolizumab will be administered every three weeks for up to 24 months, as is standard of care; PV-10 will be administered on the same schedule for the first 15 weeks to all of the subject’s skin lesions. Subjects in Phase 1b will receive both PV-10 and pembrolizumab, whereas in Phase 2 subjects will be randomized to PV-10 + pembrolizumab or pembrolizumab alone."

Pete Culpepper, CFO and COO of Provectus, noted, "This study is both scientifically and commercially important to Provectus. Scientifically, combination therapy in cancer treatment is a rapidly maturing area, where rational combination of agents is replacing the empirical approaches of the past. Commercially, this is the second of three steps that we hope will significantly strengthen our hand in negotiating a co-development transaction with an immunotherapy-focused partner. Our joint patent with Pfizer was the first; this study is the second; and the third is our immune mechanism of action clinical study, which is underway at the Moffitt Cancer Center and which has completed recruitment."

The mechanism of action study’s preliminary clinical findings, reported last year, showed that the immunologic effects of tumor ablation with PV-10 may be complementary to immune checkpoint inhibition. Companion pre-clinical testing of PV-10 in murine models of melanoma, also reported last year, showed that the therapeutic effects of PV-10 and immune checkpoint inhibition are increased when the two are used in combination.

The cost of pembrolizumab is reimbursed so it is not paid for by Provectus and the remaining cost of this study is budgeted with existing cash on hand of the Company.

For further details on the protocol visit View Source

Clovis Oncology Announces Data Presentations at 2015 European Cancer Congress

On September 23, 2015 Clovis Oncology (NASDAQ:CLVS) reported that three oral presentations and four scientific posters highlighting updated results from clinical studies of the company’s two compounds in advanced clinical development are being presented at the 2015 European Cancer Congress (ECC), which will take place Sept. 25-29 in Vienna, Austria (Press release, Clovis Oncology, SEP 23, 2015, View Source;p=RssLanding&cat=news&id=2089808 [SID:1234507525]).

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"We are pleased to have the opportunity to share significant clinical progress across our product pipeline at ECC this year," said Patrick J. Mahaffy, CEO and President of Clovis Oncology. "Some key highlights include updated results from our rucaparib studies in the treatment of advanced ovarian cancer, including ARIEL2, for which we intend to file our initial regulatory submissions in the US in mid-2016."

Rucaparib, the Company’s oral, potent, small molecule inhibitor of PARP1 and PARP2 being developed for the treatment of ovarian cancer, specifically in patients with tumors with BRCA mutations and other DNA repair deficiencies beyond BRCA such as high genomic LOH (also referred to as "BRCA-like"), is the subject of two oral presentations and two posters:

Abstract #2700 – Final results of ARIEL2 (Part 1): a Phase 2 trial to prospectively identify ovarian cancer (OC) responders to rucaparib using tumor genetic analysis

R Kristeleit
Tuesday, Sept. 29, 9-9:15am CEST
Room: Hall A2

Abstract #2701 – Quantification of genomic loss of heterzygosity enables prospective selection of ovarian cancer patients who may derive benefit from the PARP inhibitor rucaparib

A Oza
Tuesday, Sept. 29, 9:15-9:30am CEST
Room: Hall A2

Poster # P409 – A phase 2 open-label, multicenter study of single-agent rucaparib in the treatment of patients with relapsed ovarian cancer and a deleterious BRCA mutation

R Shapira-Frommer
Monday, Sept. 28, 2015, 9:15-11:15am CEST
Room: Hall C

Rociletinib, the Company’s oral, potent, mutant-selective inhibitor of epidermal growth factor receptor (EGFR) under investigation for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC), is the subject of one oral and three posters presentations:

Abstract #3009 – Activity of rociletinib in EGFR mutant NSCLC patients with a history of CNS involvement

A Varga
Monday, Sept. 28, 10:10-10:25am CEST
Room: Strauss

Poster # P356 – Rociletinib treatment and outcomes in non-small cell lung cancer (NSCLC) patients with negative central testing for T790M

B Soloman
Sunday, Sept. 27, 9:15-11:15am CEST
Room: Hall C

Poster # P356 – Efficacy of rociletinib (CO-1686) in EGFR-mutant non-small cell lung cancer (NSCLC) patients assessed with a plasma EGFR test

S Gadgeel
Sunday, Sept. 27, 9:15-11:15am CEST
Room: Hall C

Poster # P357 – Dose optimization of rociletinib for EGFR mutated NSCLC: Benefit/risk analysis from the TIGER-X trial

JC Soria
Sunday, Sept. 27, 9:15-11:15am CEST
Room: Hall C

About Rucaparib

Rucaparib is an oral, potent small molecule inhibitor of PARP1 and PARP2 being developed for the treatment of ovarian cancer, specifically in patients with tumors with BRCA mutations and other DNA repair deficiencies beyond BRCA, such as high genomic LOH, which is commonly referred to as "BRCA-like." Rucaparib was granted Breakthrough Therapy designation by the U.S. FDA in April 2015.

About Rociletinib

Rociletinib is an oral, potent, mutant-selective inhibitor of epidermal growth factor receptor (EGFR) under investigation for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC). Rociletinib targets the activating mutations of EGFR (L858R and Del19), while also inhibiting the dominant acquired resistance mutation, T790M, which develops in approximately 60 percent of patients treated with first- and second-generation EGFR inhibitors, while sparing wild-type, or "normal" EGFR at anticipated therapeutic doses. Rociletinib was granted Breakthrough Therapy designation by the U.S. FDA in May 2014.

Amgen To Present New Kyprolis® (carfilzomib) Data At 15th International Myeloma Workshop

On September 23, 2015 Amgen (NASDAQ:AMGN) reported the presentation of several studies evaluating Kyprolis (carfilzomib) for Injection, a next-generation proteasome inhibitor, at the 15th International Myeloma Workshop (IMW), from Sept. 23-26, 2015, in Rome (Press release, Amgen, SEP 23, 2015, View Source;p=RssLanding&cat=news&id=2089855 [SID:1234507524]). Kyprolis is approved in the United States (U.S.) for use in combination with lenalidomide and dexamethasone for the treatment of relapsed multiple myeloma, an incurable blood cancer. In the European Union (EU), Kyprolis is under accelerated assessment with the European Medicines Agency (EMA).

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"Multiple myeloma 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," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Data to be presented at IMW will help provide further insight into the potential of Kyprolis as an important treatment option for patients living with relapsed multiple myeloma."

The following Amgen-sponsored abstracts will be presented at the meeting:

Kyprolis

Efficacy and Safety of Carfilzomib, Lenalidomide, and Dexamethasone (KRd) vs Lenalidomide and Dexamethasone (Rd) in Patients (Pts) With Relapsed Multiple Myeloma (RMM) Based on Age: Secondary Analysis From the Phase 3 Study ASPIRE (NCT01080391)
A. Palumbo, Abstract BP-051, Friday, Sept. 25, 6:40 p.m. – 7:40 p.m. CEST (Poster Area)
Superior Health-Related Quality of Life with Carfilzomib, Lenalidomide, and Dexamethasone versus Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma (MM): Results From the ASPIRE Trial
A.K. Stewart, Abstract BP-052, Friday, Sept. 25, 6:40 – 7:40 p.m. CEST (Poster Area)

Observational

Survival Analysis in Newly Diagnosed Multiple Myeloma Patients in the United States Medicare Database
A. A. Yusuf, Abstract PO-171, Thursday, Sept. 24, 6:40 – 7:40 p.m. CEST (Poster Area)
Hospitalization Rates for Newly Diagnosed Multiple Myeloma Patients in the United States Medicare Database
A.A. Yusuf, Abstract PO-179, Thursday, Sept. 24, 6:40 – 7:40 p.m. CEST (Poster Area)
In the U.S., Kyprolis is approved as a monotherapy and in combination with lenalidomide and dexamethasone. In Mexico, Israel, Argentina and Thailand, Kyprolis is approved as monotherapy for relapsed, refractory multiple myeloma. In the EU, Kyprolis is under accelerated assessment with the EMA. The EMA application for Kyprolis is based on data from the Phase 3 ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone versus Lenalidomide and Dexamethasone for the treatment of PatIents with Relapsed Multiple MyEloma) trial and other relevant data. The study showed that patients treated with Kyprolis in combination with Revlimid (lenalidomide) and low-dose dexamethasone (regimen referred to as KRd) lived 50 percent longer (8.7 months) without their disease worsening compared to patients treated with lenalidomide and low-dose dexamethasone alone (regimen referred to as Rd). The median progression free survival was 26.3 months in those treated with KRd compared to 17.6 months in those treated with Rd (HR=0.69; 95 percent CI: 0.57-0.83; p<0.0001). The most common adverse events in the Kyprolis arm included pneumonia (1 percent), myocardial infarction (0.8 percent) and upper respiratory tract infection (0.8 percent).

About Multiple Myeloma
Multiple myeloma is the second most common hematologic cancer.1 Worldwide, more than 230,000 people are living with multiple myeloma with approximately 114,000 new cases diagnosed and 80,000 people dying of the disease each year.2,3 In the U.S., there are nearly 96,000 people living with, or in remission from, multiple myeloma.4 The estimated number of new cases of multiple myeloma in 2014 was more than 24,000 and the estimated number of deaths was 11,090.4 In Europe, it is estimated that more than 89,000 people are living with multiple myeloma. Approximately 39,000 new cases were diagnosed and 24,000 people died in 2012.3

About ASPIRE
The international, randomized Phase 3 ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone versus Lenalidomide and Dexamethasone for the treatment of PatIents with Relapsed Multiple MyEloma) trial evaluated Kyprolis in combination with lenalidomide and low-dose dexamethasone, versus lenalidomide and low-dose dexamethasone alone, in patients with relapsed multiple myeloma following treatment with one to three prior regimens. The primary endpoint of the trial was progression-free survival (PFS), defined as the time from treatment initiation to disease progression or death. Secondary endpoints included overall survival (OS), overall response rate (ORR), duration of response (DOR), disease control rate, health-related quality of life (HR-QoL) and safety. Patients were randomized to receive Kyprolis (20 mg/m2 on days 1 and 2 of cycle one only, escalating to 27 mg/m2 subsquently), in addition to a standard dosing schedule of lenalidomide (25 mg per day for 21 days on, 7 days off) and low-dose dexamethasone (40 mg per week in 4 week cycles), versus lenalidomide and low-dose dexamethasone alone. In the Kyprolis arm, patients were given a 10 minute infusion on days 1, 2, 8, 9, 15 and 16. Kyprolis was omitted on days 8 and 9 during cycles 13-18 and not administered beyond 18 cycles.The study randomized 792 patients at sites in North America, Europe and Israel.

The OS results did not cross the pre-specified early stopping boundary for the interim analysis. At the time of the interim analysis, there were 143 deaths (36.1 percent) in the KRd group, compared to 162 deaths (40.9 percent) in the Rd group. The ORR was 87 percent with KRd and 67 percent with Rd. In the KRd and Rd groups, 32 percent versus 9 percent of patients achieved a complete response or higher (stringent complete response [sCR] or complete response [CR]), a measurement indicating depth of response. Median DOR was 28.6 months for patients receiving KRd (95 percent CI, 24.9 to 31.3 months) and 21.2 months for patients receiving Rd (95 percent CI, 16.7 to 25.8 months).

The rate of deaths due to adverse events (AEs) within 30 days of the last dose was balanced between the KRd arm and the Rd arm. The most common causes of death occurring in patients in the KRd arm compared to the Rd arm included cardiac disorders (3 percent versus 2 percent), infection (2 percent versus 3 percent), renal (0 percent versus less than 1 percent) and other AEs (2 percent versus 3 percent). Serious AEs were reported in 60 percent of the patients in the KRd arm and 54 percent of the patients in the Rd arm. The most common serious AEs reported in the KRd arm compared to the Rd arm were pneumonia (14 percent versus 11 percent), respiratory tract infection (4 percent versus 1.5 percent), pyrexia (4 percent versus 2 percent) and pulmonary embolism (3 percent versus 2 percent). Discontinuation due to any AE occurred in 26 percent of patients in the KRd arm versus 25 percent of patients in the Rd arm. Adverse events leading to discontinuation of Kyprolis occurred in 12 percent of patients.

The ASPIRE data were presented at the 56th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) and published in The New England Journal of Medicine in December 2014.

About Kyprolis (carfilzomib) for Injection
Kyprolis (carfilzomib) for Injection is indicated in 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 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, Mexico and Thailand. For more information about Kyprolis, visit www.kyprolis.com.

Important Safety Information Regarding Kyprolis (carfilzomib) for Injection U.S. Indication
This safety information is specific to the current U.S. approved indication.

Cardiac Toxicities
New onset or worsening of preexisting 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 neuroradiological 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.

Lytix Biopharma presents initial results from LTX-315 Phase I study at ECC2015

On September 23, 2015 Lytix reported they will present initial safety and efficacy data from the ongoing Phase I monotherapy trial with LTX-315 as a poster presentation at the 18th European Cancer Congress (ECC2015) in Vienna on September 26 (Press release, Lytix Biopharma, SEP 23, 2015, View Source [SID:1234507523]). These results follow the Proof of Concept declared in April 2015, after the immunotherapeutic oncolytic peptide showed a favorable safety profile and emerging evidence of clinical anti-tumour activity and immune effects. Adding to the strong preclinical synergy with LTX-315 and immune checkpoint inhibitors (ICIs), Lytix also presses forward with its plans to initiate the first combination trial early 2016.

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LTX-315 induces a potent stimulation of an extended range of tumour-specific T-cells attacking cancer, potentially increasing immune response in patients. It appears LTX-315 "pushes the accelerator" of the immune system through the release of potent immune stimulants. Furthermore, LTX-315 differentiates from many other cancer immunotherapies by inducing the release of an extended range of patient-specific tumour antigens.

Combinations of complementary immunotherapy treatments are expected to be an integral part of future cancer treatment delivering significant clinical benefit. ICIs "release the brakes" imposed by the tumour on the immune system. LTX-315 has the potential to augment efficacy of ICIs without adding toxicity.

Dr. James Spicer (King’s College London at Guys Hospital London, UK), principal investigator of the Phase I study and presenter at ECC2015 commented:

"Emerging evidence of anti-tumour activity and immune effects have been observed with LTX-315 in the ongoing Phase I study. With a manageable and predictable safety profile it is both attractive and appropriate to explore combination therapy of LTX-315 with immune checkpoint inhibitors."

Dr. Andrew Saunders, CMO of Lytix Biopharma commented on the development of LTX-315:

"We are moving forward rapidly in completing the Phase I study. We have 7 active centers and 2 new centers joining the study in EU and have filed an IND to have US participation. Based on these data, and the complementary mode of action to immune checkpoint inhibitors, we are planning to initiate a combination trial program."

CTI BioPharma To Submit NDA For Pacritinib In Q4 Based Primarily On Data From Single Pivotal Persist-1 Trial

On September 23, 2015 CTI BioPharma Corp. (CTI BioPharma) (NASDAQ and MTA: CTIC) reported its plan to submit a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) following a productive pre-NDA meeting for pacritinib, an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R (Press release, CTI BioPharma, SEP 23, 2015, View Source [SID:1234507526]).

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The company expects to submit the NDA in the fourth quarter of 2015 and to request accelerated approval for the treatment of patients with intermediate and high-risk myelofibrosis with low platelet counts of less than 50,000 per microliter (<50,000/uL). The NDA will be based primarily on data from the PERSIST-1 Phase 3 trial – as well as data from Phase 1 and 2 studies of pacritinib – and additional information requested by the FDA, including a separate study report and datasets for the specific patient population with low platelet counts of less than 50,000 per microliter (<50,000/uL) for whom there are no approved drugs. Submission of an NDA after a single Phase 3 trial under accelerated approval, instead of waiting to complete two Phase 3 trials, could potentially reduce time to market by up to 14 months.

Myelofibrosis is a rare and serious chronic blood cancer that can affect patients of all ages with a median age of 65 years, with an estimated prevalence in the United States of approximately 18,000 patients.

"This improved timing on the plan to submit an NDA – which is supported by data after completion of the PERSIST-1 trial – will allow us the potential for making pacritinib available to patients with low platelet counts earlier than expected," said James A. Bianco, M.D., President and CEO of CTI BioPharma. "We look forward to working with the FDA on the submission and review of this application."

PERSIST Update

Pacritinib is currently being evaluated in two Phase 3 clinical trials, known as the PERSIST program, for patients with myelofibrosis. PERSIST-1 is a randomized, open-label, multicenter Phase 3 trial comparing the efficacy and safety of pacritinib with that of best available therapy (exclusive of a JAK inhibitor) in 327 enrolled patients with myelofibrosis (primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis), regardless of the patients’ platelet counts. PERSIST-2 is a randomized, open-label, multicenter Phase 3 clinical trial evaluating pacritinib compared to best available therapy (BAT), including the approved JAK1/JAK2 inhibitor dosed according to product label for patients with myelofibrosis whose platelet counts are less than or equal to 100,000 per microliter. In October 2013, CTI BioPharma reached agreement with the FDA on a Special Protocol Assessment (SPA) for the PERSIST-2 trial. The SPA is a written agreement between CTI BioPharma and the FDA regarding the design, endpoints and planned statistical analysis approach of the trial to be used in support of a potential NDA submission. The design of PERSIST-1 and PERSIST-2 allows for patients on the BAT arm to crossover and receive treatment with pacritinib if their disease progresses or after they achieve the 24-week measurement endpoint. Although crossover design of clinical trials may confound evaluation of survival, such designs are frequently used in cancer studies, and the FDA has approved multiple oncology drugs that utilized crossover design in Phase 3 trials. The Independent Data Monitoring Committee (IDMC) for the PERSIST program recommended patients on the best available therapy arm should not crossover to receive pacritinib due to non-statistically significant safety concerns in patients who crossover after 24 weeks, which crossover confounds evaluation of survival. After receiving input from external independent experts and providing the FDA the PERSIST-1 data, IDMC’s recommendation and correspondence, CTI BioPharma and Baxalta notified the FDA of the decision to proceed per protocol. Following a written response in lieu of a Type C meeting with the FDA, CTI BioPharma and Baxalta determined that no modifications to the ongoing trials were required. Enrollment in PERSIST-2, which is designed to enroll up to 300 patients in North America, Europe, Australia, New Zealand and Russia is continuing. Based on current timelines, PERSIST-2 enrollment is expected to be completed in the first quarter of 2016. Additional details on PERSIST-2 are available at www.clinicaltrials.gov or www.PERSISTprogram.com.

About Pacritinib
Pacritinib is an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R. In August 2014, pacritinib was granted Fast Track designation by the FDA for the treatment of intermediate and high risk myelofibrosis, including but not limited to patients with disease-related thrombocytopenia, patients experiencing treatment-emergent thrombocytopenia on other JAK2 inhibitor therapy, or patients who are intolerant of, or whose symptoms are sub-optimally managed on other JAK2 inhibitor therapy. The FDA’s Fast Track process is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Pacritinib does not have regulatory approval and is not commercially available.

CTI BioPharma and Baxalta (NYSE:BXLT) are parties to a worldwide license agreement to develop and commercialize pacritinib. CTI BioPharma and Baxalta will jointly commercialize pacritinib in the U.S. while Baxalta has exclusive commercialization rights for all indications outside the U.S.