On October 18, 2018 Delcath Systems, Inc. (OTCQB: DCTH), an interventional oncology company focused on the treatment of primary and metastatic liver cancers, reported that patient treatments have begun in the Company’s second global US registration trial investigating Melphalan Hydrochloride for Injection for use with the Delcath Hepatic Delivery System (Melphalan/HDS) in the treatment of patients with intrahepatic cholangiocarcinoma (ICC) (Press release, Delcath Systems, OCT 18, 2018, View Source;p=RssLanding&cat=news&id=2372259 [SID1234530000]).

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The University of Tennessee Health Science Center (UTHSC) in collaboration with Methodist University Hospital (MUH) and West Cancer Center (WCC) in Memphis, Tennessee have enrolled the trial’s first patient and treatments have begun by a team led by Dr. Evan S. Glazer. Dr. Glazer, a board certified surgical oncologist, is the principal investigator for the trial at the UTHSC/MUH/WCC location.

The trial, entitled A Randomized, Controlled Study to Compare the Efficacy, Safety and Pharmacokinetics of Melphalan/HDS Treatment Given Sequentially Following Cisplatin/Gemcitabine versus Cisplatin/Gemcitabine (Standard of Care) in Patients with Intrahepatic Cholangiocarcinoma, (the ALIGN Trial) will seek to enroll approximately 295 ICC patients at approximately 40 clinical sites in the U.S. and Europe.

"ICC is a deadly form of liver cancer, and the current treatment options have only shown very limited benefit," said Dr. Evan Glazer, "Our team is encouraged by the initial data available for Melphalan/HDS and are pleased to participate in this trial to explore this therapy’s potential as a new treatment option for these patients. We are most excited by the multi-disciplinary approach that this trial takes to help our patients."

"We are delighted to be working with Dr. Glazer and the team in Memphis to initiate The ALIGN Trial," said Jennifer K. Simpson, PhD, MSN, CRNP, President and Chief Executive Officer of Delcath Systems. "In this orphan population where there exists a large unmet need, this trial provides us with a potential second pathway to commercial drug approval in the United States, and if successful we believe will be an important value driver for Delcath."

On October 18, 2018 DXC Technology (NYSE: DXC), the world’s leading independent, end-to-end IT services company, reported that it will release financial results for the second quarter of fiscal 2019 on Tuesday, November 6, 2018, at approximately 4:15 p.m. Eastern Standard Time (EST) (Press release, DynPort Vaccine Company, OCT 18, 2018, View Source [SID1234529972]).

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DXC Technology senior management will host a conference call and webcast on the same day at 5 p.m. EST. The dial-in number for domestic callers is (877) 260-1479. Callers who reside outside of the United States should dial +1 (334) 323-0522. The passcode for all participants is 4189723. The webcast audio and any presentation slides will be available on DXC Technology’s Investor Relations website.

A replay of the conference call will be available from approximately two hours after the conclusion of the call until November 13, 2018. Replay numbers can be found at the following link. The replay passcode is also 4189723.

DXC Technology Investor Day

DXC Technology will host its 2018 Investor Day on Thursday, November 8, 2018 in New York City, with presentations beginning at approximately 9:30 a.m. Eastern Standard Time (EST).

A webcast of the Investor Day and any presentation slides will be available on DXC’s Investor Relations website. The webcast will begin on Thursday, November 8, 2018 at 9:30 a.m. EST at View Source

On October 18, 2018 Hutchison China MediTech Limited ("Chi-Med") (AIM/Nasdaq: HCM) reported that it has initiated a Phase I study of HMPL-523, its novel spleen tyrosine kinase ("Syk") inhibitor, in combination with azacitidine, an approved nucleoside metabolic inhibitor, in elderly patients with acute myeloid leukemia ("AML") in China (Press release, Hutchison China MediTech, OCT 18, 2018, https://www.chi-med.com/phasei-hmpl523-azacitidine-aml-china/ [SID1234529956]).

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This is a Phase I, open-label, non-randomized, multicenter study to evaluate the safety, pharmacokinetics and preliminary efficacy of the combination in previously untreated elderly patients with AML who are not eligible for standard induction therapy. The primary outcome measures are overall response rate (ORR) and adverse events (AE). The two-stage study will have a dose escalation and dose expansion stage. Additional details about this study may be found at clinicaltrials.gov, using identifier NCT03483948.

This study complements the ongoing Phase Ib dose expansion program of HMPL-523 in a broad range of hematological cancers in Australia (clinicaltrials.gov identifier: NCT02503033) and China (clinicaltrials.gov identifier: NCT02857998). These include chronic lymphocytic leukemia, small lymphocytic lymphoma, mantle cell lymphoma, follicular lymphoma, marginal zone lymphoma, diffuse large B-cell lymphoma and Waldenstrom’s macroglobulinemia. Chi-Med targets to present dose escalation results at a major scientific conference later in 2018 or in 2019. Chi-Med’s U.S. Investigational New Drug (IND) application for HMPL-523 in hematological cancers was cleared by the Food and Drug Administration (FDA) at the end of June 2018 and hence Chi-Med is now planning for proof-of-concept development in the U.S.

About Syk
Syk is a non-receptor cytoplasmic tyrosine kinase primarily expressed in cells of hematopoietic lineage. Constitutive activation of Syk in AML has been reported and targeted inhibition of Syk demonstrated anti-leukemia activity in AML mouse models. Syk has also been shown to directly phosphorylate the FLT3 receptor, modulating its activation and possibly promoting its role in leukemogenesis.

About AML
AML, a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia. Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells. AML occurs in children and adults of all ages, but is primarily a disease of older adults, with a median age at diagnosis of 67 years. AML is universally fatal without treatment, with a median survival of approximately two months.[i] The vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML. The five-year survival rate for AML is approximately 27%.[ii]

Combination chemotherapy regimens with or without hematopoietic stem cell transplantation (HSCT) are a mainstay of therapy for patients with newly diagnosed AML. Older patients with newly diagnosed AML who are ineligible for intensive chemotherapy typically have poor outcomes and few available treatment options. There is a clear need for new treatments for AML.

On October 18, 2018 Novartis reported that it has entered into an agreement and plan of merger with Endocyte, a US-based biopharmaceutical company focused on developing targeted therapeutics for cancer treatment (Press release, Novartis, OCT 18, 2018, View Source [SID1234529973]). Under the terms of the agreement, Novartis would acquire all outstanding shares of Endocyte common stock for USD 24 per share. This offer values Endocyte’s equity at USD 2.1 billion.

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Endocyte uses drug conjugation technology to develop targeted therapies with companion imaging agents, including 177Lu-PSMA-617, a potential first-in-class investigational radioligand therapy (RLT) for the treatment of metastatic castration-resistant prostate cancer (mCRPC). 177Lu-PSMA-617 targets the prostate-specific membrane antigen (PSMA), present in the majority of patients with mCRPC, and has shown promising Phase II data. 177Lu-PSMA-617 is currently being investigated in the Phase III global VISION clinical trial in men with mCRPC, a disease with limited treatment options and significant unmet medical need.

If completed, the Endocyte acquisition would expand the Novartis RLT platform with both a potential near-term product launch and early-stage clinical development programs. The deal would also enable Novartis to harness its research and development expertise to investigate the potential development of 177Lu-PSMA-617 for use in earlier lines of prostate cancer therapy.

Liz Barrett, CEO, Novartis Oncology, said, "Novartis has a strong legacy of addressing unmet needs with transformative therapies and is building a leadership capability in new, technology-driven platforms that address some of the world’s most complex health challenges, including cancer. Today’s announcement about the proposed acquisition of Endocyte builds on our growing capability in radiopharmaceuticals, which is expected to be an increasingly important treatment option for patients and a key growth driver for our business. We are also excited about the opportunity to break into the prostate cancer arena with a near-term product that has the potential to make a meaningful impact for patients in great need of more options."

In a Phase II study, 50 patients with PSMA-positive mCRPC treated with 177Lu-PSMA-617 showed a median prostate specific antigen (PSA) progression free survival (PFS) of 7.6 months (p<0.0001).[1] Median overall survival for the first cohort of 30 patients enrolled was 13.5 months (p=0.0201).[1]

VISION is a global, prospective, open-label, multi-center, randomized Phase III trial of 177Lu-PSMA-617 in combination with best supportive care versus best supportive care alone. The trial is currently enrolling patients with mCRPC. In September, the US Food and Drug Administration (FDA) agreed to radiographic progression-free survival (rPFS) as an alternative primary endpoint to OS in the trial.

The Endocyte pipeline includes additional investigational RLTs, including 225Ac-PSMA-617 in preclinical studies for the treatment of mCRPC.

Radiopharmaceuticals such as 177Lu-PSMA-617 are innovative medicinal formulations containing radioisotopes that are used clinically for both diagnosis and therapy.

Through the acquisition of Advanced Accelerator Applications (AAA), Novartis acquired Lutathera (lutetium Lu 177 dotatate / INN: lutetium (177Lu) oxodotreotide) – the first ever approved Peptide Receptor Radionuclide Therapy – for the treatment of somatostatin-receptor positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), an orphan disease.

Transaction Details
The transaction would be in the form of a merger of Endocyte and a newly formed Novartis subsidiary. Under the terms of the agreement and plan of merger, upon closing, holders of Endocyte common stock would receive USD 24 in cash per share. This offer values Endocyte’s equity at USD 2.1 billion.

Closing of the transaction is subject to customary closing conditions, including the approval of Endocyte’s stockholders and receipt of regulatory approvals. Until closing, Endocyte will continue to operate as a separate and independent company.

The acquisition of Endocyte is planned to be funded through available cash.

On October 18, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that the first patient has been dosed in a first-in-human phase 1 study assessing the safety and tolerability of DS-1205, a highly selective investigational AXL inhibitor, in combination with gefitinib in patients with metastatic or unresectable epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who have progressed on therapy with tyrosine kinase inhibitors (TKIs) (Press release, Daiichi Sankyo, OCT 18, 2018, View Source [SID1234530247]).

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For patients with metastatic EGFR-mutated NSCLC, targeted EGFR TKI therapies such as gefitinib, erlotinib, afatinib or osimertinib represent the first-line treatment of choice.3,4,5,6 However, patients eventually develop resistance to these treatments, typically experiencing disease progression within a year.3,4,5,6 Once a patient is resistant to all possible EGFR TKIs, there are limited treatment options, including chemotherapy, immunotherapy or investigational agents.3,6 Research suggests that inhibition of AXL, a receptor tyrosine kinase, may help delay or overcome the onset of resistance to the TKIs.1,2

"This first-in-human trial will build upon preclinical research to evaluate the potential of our AXL inhibitor, DS-1205, in combination with gefitinib in EGFR-mutated NSCLC that has progressed on TKI therapy," said Eric Slosberg, PhD, Head, Oncology Translational Development, Oncology Research and Development, Daiichi Sankyo. "We are evaluating for the first time in a clinical setting whether inhibition of the AXL pathway with DS-1205 may help prevent, delay or overcome the onset of resistance to EGFR TKIs, as we continue to research and develop new targeted therapy approaches for patients with metastatic NSCLC."

About the DS-1205 and Gefitinib Combination Study

The multicenter phase 1, open-label, two-part study will enroll patients with metastatic or unresectable EGFR-mutated NSCLC who have T790M mutation-negative tumors and have experienced disease progression during treatment with erlotinib, gefitinib or afatinib, or developed disease progression while on osimertinib. The first part of the study (dose escalation) will assess the safety, tolerability, pharmacokinetics and efficacy of DS-1205 in combination with gefitinib to determine the recommended dose for expansion. The second part of the study (dose expansion) will evaluate the safety, tolerability, pharmacokinetics and efficacy of the combination therapy. Study endpoints include safety, pharmacokinetics, objective response rate, duration of response, disease control rate, time to response, progression-free survival, overall survival and exploratory biomarker analyses. The study is expected to enroll approximately 60 patients at approximately 20 sites in Japan and other countries. For more information on the clinical trial, visit ClinicalTrials.gov.

Unmet Need in EGFR-Mutated Metastatic NSCLC

Lung cancer is the most common cancer in the world and the leading cause of cancer deaths.7, 8 There were approximately 1.8 million new cases of lung cancer reported globally and 1.69 million deaths from lung cancer in 2012.8 NSCLC is the most common form of lung cancer, accounting for approximately 80 to 85 percent of all cases. It is difficult to treat, particularly in advanced disease, and the five-year survival rate for metastatic NSCLC is only one percent.9

In the past decade, significant improvements in treatment have occurred due to the development of targeted therapies, such as EGFR TKIs, for advanced NSCLC.3 EGFR mutations have been reported in a wide range of NSCLC patients (from 10 to 50 percent), and frequency may vary based on ethnicity and other factors.3,10

While the majority of patients with EGFR-mutated tumors respond to EGFR TKIs, resistance eventually develops in more than half of these patients, and they typically experience disease progression within a year.11 Resistance may be acquired or intrinsic.3 The most common mechanism for acquired resistance to gefitinib, erlotinib or afatinib involves a secondary EGFR mutation called T790M, which may be treated with the EGFR TKI osimertinib.3,4,5,6 However, patients who experience disease progression following treatment with gefitinib, erlotinib or afatinib and whose tumors lack the T790M mutation, and patients who experience disease progression following osimertinib treatment have limited options such as chemotherapy, immunotherapy or investigational treatments.5,6

Researchers are exploring specific therapeutic strategies to overcome acquired resistance to EGFR TKIs.3 Studies have demonstrated that up-regulation of AXL, a receptor tyrosine kinase, may develop in some patients with EGFR-mutated NSCLC who experience disease progression on TKI therapy, and this up-regulation might be a mechanism of resistance to EGFR TKI treatment.11,12,13 Accordingly, inhibition of AXL might restore sensitivity to EGFR TKI treatment.11 While preclinical research has demonstrated that inhibition of AXL by DS-1205 restored sensitivity to erlotinib and the addition of DS-1205 to TKI therapy at the beginning of treatment delayed the onset of resistance to gefitinib, erlotinib or osimertinib, it is as yet to be confirmed that DS-1205 will work similarly in humans.1,2

Abnormal expression and activation of AXL have been correlated with poor prognosis, increased growth and metastasis, and drug resistance in many cancers including NSCLC.12,13

About DS-1205

Part of the investigational Breakthrough Science pipeline of Daiichi Sankyo Cancer Enterprise, DS-1205 is an investigational highly selective AXL inhibitor currently being evaluated in a phase 1 clinical study in combination with gefitinib for metastatic or unresectable EGFR-mutated NSCLC. DS-1205 is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.