On May 29, 2017 Takara Bio Inc. (Takara Bio), reported that the first patient with melanoma has been enrolled into Oncolytic Virus HF10(TBI-1401) phase II clinical trial in Japan on May 26, 2017 (Press release, Takara Bio, MAY 29, 2017, View Source [SID1234519312]).

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In this clinical study, HF10 is administered in combination with Ipilimumab in patients with unresectable or metastatic melanoma, and its efficacy and safety will be evaluated as well as immunological test. Also, the HF10 manufactured at Center for Gene and Cell, Takara Bio’s facility, is used in this study.

Takara Bio attempts to achieve the accelerated approval utilizing the conditional and term-limited approval system for regenerative medicine under "The Law on Securing Quality, Efficacy and Safety of Products including Pharmaceuticals and Medical devices". Takara Bio aims to commercialize the HF10 cancer therapy in the fiscal year 2018 in Japan.

On May 29, 2017 – Apogenix AG, a biopharmaceutical company developing next-generation immuno-oncology therapeutics, reported that it has been awarded PRIME (PRIority MEdicines) designation by the European Medicines Agency (EMA) for its lead product candidate, asunercept (APG101), for the treatment of glioblastoma. The PRIME designation was based on the results of a Phase 2 trial (APG101_CD_002) of 86 adult patients with relapsed glioblastoma treated with asunercept. Data from this trial have been published in a peer-reviewed medical journal (Clin Cancer Res. 2014 Dec 15;20(24):6304-13) (Press release, Apogenix, MAY 29, 2017, View Source [SID1234519313]).

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In March 2016, the EMA launched the PRIME program to enhance support for the development of medicines that target an unmet medical need. Eligibility criteria are similar to those of the U. S. Food and Drug Administration (FDA) breakthrough therapy program. The goal of the PRIME program is to help patients to benefit as early as possible from therapies that may significantly improve their quality of life. The program focuses on medicines that may offer a major therapeutic advantage over existing treatments, or benefit patients without treatment options. These medicines are considered priority medicines by EMA. To be accepted for PRIME, a medicine has to show its potential to benefit patients with unmet medical needs based on early clinical data. Since the inception of the program in March 2016 only 2 3 % (2 5 of 108) of requests were granted for access to the program (www.ema.europa.eu/docs/en_GB). Through PRIME, the a gency offers early and proactive support to medicine developers to optimize the generation of robust data on a medicine’s benefits and risks and enable accelerated assessment of marketing applications.

"There is a high unmet need for new medicines to treat glioblastoma patients, who have very few treatment options. The PRIME designation by the EMA supports our belief that asunercept has the potential to improve the lives of patients suffering from glioblastoma, a deadly form of brain cancer,"said Harald Fricke, M.D., Chief Medical Officer of Apogenix. "We are committed to working closely with the agency to make asunercept available to patients as expeditiously as possible."

About glioblastoma
Glioblastoma is an aggressive form of brain cancer that quickly spread s into other parts of the brain. In the US, an estimated 23,800 new cases of brain and central nervous system cancers are expected in 2017 and 16,700 deaths due to the disease. The five-year survival rate is less than 35%. In the European Union (EU-28) recent statistics indicate over 43,000 cases and nearly 33,000 deaths due to the disease. Treatment options today involve surgery, radiation therapy and/or chemotherapy, but these treatments are often inadequate and there remains a major need for more effective treatments.

About a sunercept (APG101)
Apogenix’s lead immuno-oncology candidate asunercept is a fully human fusion protein that consists of the extracellular domain of the CD95-receptor and the Fc domain of an IgG1 antibody. Asunercept is being developed for the treatment of solid tumors and malignant hematological diseases. The World Health Organization (WHO) has assigned the international nonproprietary name (INN) "asunercept" for APG101.

On May 26, 2017 Novartis reported the US Food and Drug Administration (FDA) approved the expanded use of Zykadia (ceritinib) to include the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive, as detected by an FDA-approved test (Press release, Novartis, MAY 26, 2017, View Source [SID1234519304]). Zykadia first received accelerated approval in 2014 for patients with ALK-positive metastatic NSCLC who progressed on or are intolerant to crizotinib. In January 2017, the FDA granted Zykadia Breakthrough Therapy designation for the first-line treatment of patients with ALK-positive metastatic NSCLC with metastases to the brain, and Priority Review for first-line ALK-positive metastatic NSCLC.

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The first-line approval of Zykadia is based on results from an open-label, randomized, multicenter, global, Phase III trial, ASCEND-4. The study demonstrated that patients treated with first-line Zykadia had a median progression-free survival (PFS) of 16.6 months (95% confidence interval [CI]: 12.6, 27.2), compared to 8.1 months (95% CI: 5.8, 11.1) for patients treated with standard first-line pemetrexed-platinum chemotherapy with pemetrexed maintenance[1].

Overall intracranial response rate (OIRR) in patients with measurable brain metastases was 57% (95% CI: 37, 76; n = 28) for patients treated with Zykadia, versus 22% (95% CI: 9, 42; n = 27) for patients treated with chemotherapy[1]. The whole body overall response rate (ORR) was 73% (95% CI: 66, 79; n = 187) in patients treated with Zykadia[1].

"Today’s approval represents the next step in the development of Zykadia as a treatment option for ALK-positive metastatic NSCLC, bringing this important medication to a patient population where a need still exists," said Bruno Strigini, CEO, Novartis Oncology. "At Novartis, we are tireless in our pursuit of developing novel medicines to treat lung cancer, and the first-line approval of Zykadia for ALK-positive metastatic NSCLC illustrates our commitment to cancer patients."

Approximately 3-7% of all patients with NSCLC have an ALK gene rearrangement[2]. An FDA-approved test at the time of diagnosis may help to determine the presence of this mutation and, thus, the most appropriate treatment option[3].

Novartis Commitment to Lung Cancer
Worldwide, lung cancer causes more deaths than colon, breast and prostate cancer combined, and an estimated 1.8 million new cases of lung cancer are diagnosed each year[4],[5]. Among patients with NSCLC, roughly 25% have an actionable mutation that may be targeted with available therapies[6].

Over the past decade, Novartis Oncology’s research has supported the evolution of treatment approaches for patients living with mutation-driven types of lung cancer. The company continues its commitment to the global lung cancer community through ongoing studies, as well as the exploration of investigational compounds that target genomic biomarkers in NSCLC.

About ASCEND-4
ASCEND-4 is a Phase III randomized, open-label, multicenter, global clinical trial to evaluate the safety and efficacy of Zykadia compared to standard chemotherapy, including maintenance, in adult patients with Stage IIIB or IV ALK-positive advanced NSCLC who received no prior therapy for their advanced disease. Patients received Zykadia orally at 750 mg/daily or standard pemetrexed-based platinum doublet chemotherapy (pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 or carboplatin AUC 5-6) for four cycles followed by pemetrexed maintenance.

Of 376 patients, 189 (59 with brain metastases) were randomized to Zykadia and 187 (62 with brain metastases) to chemotherapy[1]. Approximately 70% of patients with measurable brain metastases at baseline did not have prior radiation therapy, the current standard of treatment for baseline brain metastases[1]. Among patients randomized to the chemotherapy arm, 43% received Zykadia as their next treatment after platinum-based chemotherapy[1].

Patients treated with first-line Zykadia had a median PFS of 16.6 months (95% CI: 12.6, 27.2), compared to 8.1 months (95% CI: 5.8, 11.1) for patients treated with standard first-line pemetrexed-platinum chemotherapy with pemetrexed maintenance[1]. A 45% risk reduction in PFS was obtained in the Zykadia arm compared to the chemotherapy arm (hazard ratio [HR] = 0.55 [95% CI: 0.42, 0.73; one-sided p value <0.0001])[1].

Patients without brain metastases at screening receiving Zykadia experienced a median PFS of 26.3 months (95% CI: 15.4, 27.7), compared with 8.3 months (95% CI: 6.0, 13.7) among patients treated with chemotherapy (HR = 0.48 [95% CI: 0.33, 0.69])[7]. Among patients with brain metastases at screening, the median PFS was 10.7 months (95% CI: 8.1, 16.4) in the Zykadia group versus 6.7 months (95% CI: 4.1, 10.6) in the chemotherapy group (HR = 0.70 [95% CI: 0.44, 1.12])[7].

The most common adverse reactions in ASCEND-4 (incidence >=25% all grades) were diarrhea (85%), nausea (69%), vomiting (67%), fatigue (45%), abdominal pain (40%), decreased appetite (34%) and cough (25%)[1]. In ASCEND-4, Grade 3/4 adverse reactions (incidence >=2%) were fatigue (7%), vomiting (5%), diarrhea (4.8%), abdominal pain (3.7%), weight loss (3.7%), nausea (2.6%) and prolonged QT interval (2.6%)[1]. The most common laboratory abnormalities in ASCEND-4 (incidence >=25% all grades) were increased ALT/AST (91%/86%), increased GGT (84%), increased alkaline phosphatase (81%), creatinine increase (77%), anemia (67%), hyperglycemia (53%), decreased phosphate (38%), increased amylase (37%) and neutropenia (27%)[1]. In ASCEND-4, Grade 3/4 laboratory abnormalities (incidence >=2%) were increased GGT (49%), ALT/AST (34%/21%), increased alkaline phosphatase (12%), hyperglycemia (10%), increased amylase (8%), increase lipase (6%), creatinine increase (4.2%), anemia (4.2%), decreased phosphate (3.7%) and neutropenia (2.1%)[1].

About Zykadia
Zykadia is an oral, selective inhibitor of anaplastic lymphoma kinase (ALK), a gene that can fuse with others to form an abnormal "fusion protein" that promotes the development and growth of certain tumors in cancers including non-small cell lung cancer (NSCLC). Zykadia is currently approved in over 69 countries worldwide. Please visit View Source (link is external) for additional information.

Zykadia Important Safety Information
Zykadia may cause serious side effects.

Zykadia may cause stomach upset and intestinal problems in most patients, including diarrhea, nausea, vomiting and stomach-area pain. These problems can be severe. Patients should follow their doctor’s instructions about taking medicines to help these symptoms, and should call their doctor for advice if symptoms are severe or do not go away.

Zykadia may cause severe liver injury. Patients should have blood tests prior to the start of treatment with Zykadia, every two weeks for the first month of treatment and monthly thereafter, and should talk to their doctor right away if they experience any of the following symptoms: tiredness (fatigue), itchy skin, yellowing of the skin or the whites of the eyes, nausea or vomiting, decreased appetite, pain on the right side of the abdomen, urine turns dark or brown, or bleeding or bruising more easily than normal.

Zykadia may cause severe or life-threatening swelling (inflammation) of the lungs during treatment that can lead to death. Symptoms may be similar to those symptoms from lung cancer. Patients should tell their doctor right away about any new or worsening symptoms, including trouble breathing or shortness of breath, fever, cough, with or without mucous, or chest pain.

Zykadia may cause very slow, very fast, or abnormal heartbeats. Doctors should check their patient’s heart during treatment with Zykadia. Patients should tell their doctor right away if they feel new chest pain or discomfort, dizziness or lightheadedness, faint, or have abnormal heartbeats, blue discoloration of lips, shortness of breath, swelling of lower limbs or skin, or if they start to take or have any changes in heart or blood pressure medicines.

Zykadia may cause high levels of glucose in the blood. People who have diabetes or glucose intolerance, or who take a corticosteroid medicine have an increased risk of high blood sugar with Zykadia. Patients should have glucose blood tests prior to the start of treatment with Zykadia and during treatment. Patients should follow their doctor’s instructions about blood sugar monitoring and call their doctor right away with any symptoms of high blood sugar, including increased thirst and/or urinating often.

Zykadia may cause high levels of pancreatic enzymes in the blood and may cause pancreatitis. Patients should have blood tests prior to the start of treatment with Zykadia and as needed during their treatment with Zykadia. Patients should talk to their doctor if they experience signs and symptoms of pancreatitis which including upper abdominal pain that may spread to the back and get worse with eating.

Before patients take Zykadia, they should tell their doctor about all medical conditions, including liver problems; diabetes or high blood sugar; heart problems, including a condition called long QT syndrome; if they are pregnant, if they think they may be pregnant, or if they plan to become pregnant; are breastfeeding or plan to breastfeed.

Zykadia may harm unborn babies. Women who are able to become pregnant must use a highly effective method of birth control (contraception) during treatment with Zykadia and up to 3 months after stopping Zykadia. Patients and their doctor should decide whether to take Zykadia or breastfeed, but should not do both.

Patients should tell their doctor about medicines they take, including prescription medicines, over-the-counter medicines, vitamins and herbal supplements.

The most common adverse reactions with an incidence of >=10% diarrhea, nausea, vomiting, liver laboratory test abnormalities, fatigue, abdominal pain, decreased appetite, weight decreased constipation, blood creatinine increased, rash, anemia, and esophageal disorder. Grade 3-4 adverse reactions with an incidence of >=5% were fatigue, vomiting, diarrhea, abdominal pain, weight loss, nausea, and prolonged QT Interval.

Patients should stop taking Zykadia and seek medical help immediately if they experience any of the following, which may be signs of an allergic reaction:

Difficulty in breathing or swallowing
Swelling of the face, lips, tongue or throat
Severe itching of the skin, with a red rash or raised bumps
Patients should tell their doctor of any side effect that bothers them or does not go away. These are not all of the possible side effects of Zykadia. For more information, patients should ask their doctor or pharmacist.

Patients should take Zykadia exactly as their health care provider tells them. Patients should not change their dose or stop taking Zykadia unless their health care provider advises them to. Zykadia should be taken once a day on an empty stomach. Patients should not eat for at least 2 hours before and 1 hour after taking Zykadia. If a dose of Zykadia is missed, they should take it as soon as they remember. If their next dose is due within the next 12 hours, they should skip the missed dose and take the next dose at their regular time. They should not take a double dose to make up for a forgotten dose. Patients should not drink grapefruit juice or eat grapefruit during treatment with Zykadia, as it may make the amount of Zykadia in their blood increase to a harmful level. If patients have to vomit after swallowing Zykadia capsules, they should not take more capsules until their next scheduled dose.

Please see full Prescribing Information for Zykadia.

On May 26, 2017 Endocyte, Inc. (NASDAQ:ECYT), a leader in developing targeted small molecule drug conjugates (SMDCs) and companion imaging agents for personalized therapy, reported that two posters will be presented on its lead, clinical-stage assets, EC1456 and EC1169, at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held June 2 – 6, 2017, in Chicago (Press release, Endocyte, MAY 26, 2017, View Source [SID1234519303]).

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Updated data will be presented on EC1456-01, a two part phase 1 dose escalation (Part A) and expansion (Part B) study. The presentation includes data for 87 Part A treated patients with advanced solid tumors and 6 Part B treated patients with FR-positive non-small cell lung cancer (NSCLC) as of the data cutoff on May 18, 2017. All patients were imaged to assess folate receptor expression with 99mTc-etarfolatide (FR expression not an eligibility criteria for Part A). Preliminary data from our first patient enrolled in the EC1456 ovarian surgical study, EC1456-02, will also be presented.

An update also will be provided for EC1169-01, a two-part phase 1 dose escalation (Part A) and expansion (Part B) study in patients with metastatic castration-resistant prostate cancer (mCRPC). The presentation includes data for the expansion phase (Part B) for 24 taxane-exposed mCRPC patients and 16 taxane-naïve mCRPC patients as of the data cutoff on May 15, 2017. All patients were imaged to assess PSMA expression with 99mTc-EC0652 (PSMA expression not an eligibility criteria).

The posters will be available on Endocyte’s website following presentation at the conference.

Presentations are as follows:

Abstract #: 2576
Title: Phase 1 dose escalation study of the folate receptor-targeted small molecule drug conjugate EC1456
Presenter: Dr. Wael Harb, Horizon Oncology Center
When: Monday, June 5, 8:00 a.m. – 11:30 a.m. CDT
Session Title: Poster Session: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics


Abstract #: 5038
Title: Phase 1 study of the PSMA-targeted small-molecule drug conjugate EC1169 in patients with metastatic castrate-resistant prostate cancer (mCRPC)
Presenter: Dr. Michael Morris, Memorial Sloan Kettering Cancer Center
When: Monday, June 5, 1:15 p.m. – 4:45 p.m. CDT
Session Title: Poster Session: Genitourinary (Prostate) Cancer

About EC1456

EC1456 is an investigational therapeutic SMDC constructed of a high affinity FR-targeting ligand conjugated through a spacer and bioreleasable linker system to a potent cytotoxic microtubule inhibitor, tubulysin B hydrazide (TubBH). Patient FR-status is determined using the investigational companion imaging agent, etarfolatide. EC1456 is currently being evaluated in a phase 1 study in patients with advanced solid tumors (Part A) and FR-positive NSCLC (Part B) (ClinicalTrials.gov Identifier: NCT01999738) and a phase 1 exploratory study in patients with ovarian cancer undergoing surgery (ClinicalTrials.gov Identifier: NCT03011320).

About EC1169

EC1169 is an investigational therapeutic SMDC constructed of a high affinity prostate specific membrane antigen (PSMA)-targeting ligand conjugated through a bioreleasable linker system to a potent microtubule inhibitor, TubBH. Patient PSMA-status is determined using the investigational companion imaging agent, EC0652. EC1169 is currently being evaluated in a phase 1 study in patients with metastatic castration-resistant prostate cancer (mCRPC) (ClinicalTrials.gov Identifier: NCT02202447).

On May 26, 2017 Kite Pharma, Inc., (Nasdaq:KITE), a leading cell therapy company, reported that the U.S. Food and Drug Administration (FDA) has accepted for priority review the Biologics License Application (BLA) for axicabtagene ciloleucel (Press release, Kite Pharma, MAY 26, 2017, View Source [SID1234519299]). The submission follows positive data demonstrated with a single infusion of axicabtagene ciloleucel in the ZUMA-1 Phase 2 trial in patients with refractory aggressive non-Hodgkin lymphoma (NHL). The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of November 29, 2017.

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"Patients with refractory aggressive NHL face a dire prognosis with only a 50 percent chance of surviving six months. This underscores the urgent medical need for these patients and why every day matters, from development to manufacturing to clinical experience," said David Chang, M.D., Ph.D., Executive Vice President of Research and Development and Chief Medical Officer of Kite. "We firmly believe in the potential for axicabtagene ciloleucel to address this need and forge a new path for the future of cell therapy."

The filing acceptance is supported by data from the ZUMA-1 Phase 2 trial which met the primary endpoint of objective response rate (ORR) recorded after a single infusion of axicabtagene ciloleucel with 82 percent (p < 0.0001). At a median follow-up of 8.7 months, 44 percent of patients were in ongoing response, which included 39 percent of patients in complete response (CR).

The most common grade 3 or higher adverse events included anemia (43 percent), neutropenia (39 percent), decreased neutrophil count (32 percent), febrile neutropenia (31 percent), decreased white blood cell count (29 percent), thrombocytopenia (24 percent), encephalopathy (21 percent) and decreased lymphocyte count (20 percent). There were three deaths throughout the course of the registrational trial not due to disease progression, of which two events, were deemed related to axicabtagene ciloleucel.

In December 2015, axicabtagene ciloleucel received Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) for DLBCL, TFL, and PMBCL. The company expects to submit its Market Authorization Application (MAA) of axicabtagene ciloleucel with the European Medicines Agency (EMA) in the third quarter of 2017.

ZUMA-1 is supported in part by funding from The Leukemia & Lymphoma Society (LLS) Therapy Acceleration Program.

About axicabtagene ciloleucel

Kite’s lead product candidate, axicabtagene ciloleucel, is an investigational therapy in which a patient’s T cells are engineered to express a chimeric antigen receptor (CAR) to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias, and redirect the T cells to kill cancer cells. Axicabtagene ciloleucel has been granted Breakthrough Therapy Designation status for diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL) by the U.S. Food and Drug Administration (FDA) and Priority Medicines (PRIME) regulatory support for DLBCL in the EU.