On October 23, 2018 Novocure (NASDAQ: NVCR) reported that results from a post-hoc analysis of Novocure’s EF-14 phase 3 pivotal trial in newly diagnosed glioblastoma (GBM) that demonstrated that a higher dose of Tumor Treating Fields delivered to the tumor bed was associated with improved overall survival (Press release, NovoCure, OCT 23, 2018, View Source [SID1234530074]). For Tumor Treating Fields, the term delivered dose is a function of power loss density, a measure of energy, and compliance, or monthly usage of therapy. Tumor Treating Fields is a cancer therapy that uses electric fields tuned to specific frequencies to disrupt cell division, inhibiting tumor growth and causing affected cancer cells to die. The analysis was presented today at the American Society for Radiation Oncology (ASTRO) 2018 Annual Meeting in San Antonio, Texas.

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"This post-hoc analysis of EF-14 is extremely valuable to the radiation oncology community and supports the importance of targeting the tumor of each patient when planning treatment with Tumor Treating Fields," said Matt Ballo, MD, FACR, Director of Radiation Oncology at West Cancer Center in Germantown, Tennessee. "I believe an increased understanding of delivered dose will allow our treatment planning to become more sophisticated over time and help us achieve better patient outcomes."

The post-hoc analysis used patient data from the Tumor Treating Fields treatment arm of Novocure’s EF-14 phase 3 pivotal trial and included only patients who were treated for more than two months to ensure sufficient treatment duration to reach tumor stabilization and for whom quality MRI data was available. Of the 466 patients in the Tumor Treating Fields treatment arm, 379 received therapy for more than two months, and 317 of these patients had sufficient MRI quality to build head models. For each of these 317 patients, an individualized electric field distribution model within the head was created. Transducer arrays were placed on each model and simulations were run to calculate both electric field intensity and power loss density within the tumor bed. Electric field intensity measures the force acting on charges within a region of treatment and power loss density measures the amount of energy at the tumor bed. Power loss density at the tumor bed is a factor of both electric field intensity and tissue conductivity within the region of treatment.

Higher electric field intensity (≥1.0 Volts/cm) and higher power loss density (≥1.1 mW/cm3) at the tumor bed were both associated with improved overall survivals, independent of compliance, or monthly usage of therapy. Power loss density was the most significant driver with a median overall survival of 25.23 months for patients treated with Tumor Treating Fields at power loss densities greater than or equal to 1.1 mW/cm3 (n=122), compared to a median overall survival of 21 months (n=195) for patients treated with Tumor Treating Fields at power loss densities less than 1.1 mW/cm3 (HR, 0.59; 95 percent Cl, 0.43-0.81; P<.01).

A previously presented analysis of EF-14 data demonstrated that more time on Optune predicted an increased survival benefit in patients with newly diagnosed GBM. In the analysis presented today, the greatest improvement in median overall survival among all sub groups was seen in patients who both spent more time on Optune and received Tumor Treating Fields at higher power loss densities. Patients who used Optune more than 85 percent (n=36) of the time and received Tumor Treating Fields at power loss densities greater than or equal to 1.1 mW/cm3 had the greatest improvements in overall survival. Tumor Treating Fields delivered dose can now be defined as a factor of both power loss density and monthly usage of therapy.

"This analysis demonstrated a dose dependence on the overall survival of GBM patients treated with Tumor treating Fields and that improvements in overall survival were possible when patients received an increased delivered dose of Tumor Treating Fields," said Dr. Eilon Kirson, Novocure’s Chief Science Officer and Head of Research and Development. "The NovoTAL System is available to help physicians optimize and individualize treatment planning for patients by directing electric field intensity to the region of active tumor. We are committed to further developing our technology and believe increasing the power loss density of Tumor Treating Fields at the tumor bed through treatment planning has the potential to improve patient outcomes."

On October 23, 2018 Alphamab Oncology and 3D Medicines Inc. (3D Med) reported PD-L1 antibody KN035 has entered late stage clinical development, including phase III for bile tract carcinoma (cholangiocarcinoma) and phase II for MSI-H solid tumors have been initiated in China (Press release, Alphamab, OCT 23, 2018, View Source [SID1234530317]). It is also announced that the poster entitled "Phase I Study of KN035, A Novel Fusion anti-PD-L1 Antibody Administered Subcutaneously in Patients with Advanced Solid Tumors in the USA" (poster No. 1456) was presented at the 2018 Annual Congress of the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper).

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KN035 is the first-in-class PD-L1 single-domain antibody with distinct features over all other PD- (L) 1 antibodies. KN035 has the advantages of subcutaneous injection and good stability at room temperature. These would be of great value to improve patients’ compliance and quality of life and to help realize the goal of long-term management of cancer as a chronic disease. So far, more than 300 patients have participated in KN035 clinical trials in the United States, Japan and China.

The phase I trial in the United States was designed as a 3+3 open dose-escalation study in patients with advanced and inoperable tumors. The main endpoints were tolerance to KN-035 and safety, with the secondary endpoints were to evaluate the pharmacokinetic of KN-035, the maximum tolerance dose and the antitumor effect as a single drug. The drug was given subcutaneously at a dosage of 0.01, 0.03, 0.1, 0.3, 1.0, 2.5, 5.0 and 10.0 mg/kg weekly.

In the US phase I trial, a total of 18 subjects were enrolled as of July 5, 2018. In the 17 subjects who finished efficacy evaluation, 2 partial response (PR) and 5 stable disease (SD) were confirmed, according to the RECIST1.1 criterion. No dose-limiting toxicity (DLT) was observed in this trial. The exposure to KN035 increased proportionally with dose. Average half-life of KN035 was about 200 hours.

Dr. Ting Xu, Chairman and CEO of Alphamab Oncology, said, "KN035 is currently the sole PD-L1 antibody through subcutaneous injection with excellent bioavailability and distribution. We expect that the clinical progress of KN035 will further demonstrate its advantages. In addition to the indications being tested, we plan to leverage KN035’s unique profile to explore its potential utility in maintenance, adjuvant therapy and neo-adjuvant therapy. We hope to provide patients with an alternative and convenient option."

Dr. John Gong, CEO of 3D Med, added, "We are excited with the data from the phase I clinical study conducted in the US. It demonstrated the safety and good pharmacokinetics of KN035 in patients with advanced cancer, as well as encouraging initial treatment efficacy. We look forward to further advancing the KN035 clinical trials in the US with the leading oncologists there"

On October 23, 2018 Aptose Biosciences Inc. (NASDAQ: APTO; TSX: APS), a clinical-stage company developing highly differentiated therapeutics targeting the underlying mechanisms of cancer, reported that it will release its financial results for the quarter ended September 30, 2018 on Tuesday, November 6, 2018 after market hours and will hold a conference call Wednesday, November 7, 2018 at 8:00 am Eastern time (Press release, Aptose Biosciences, OCT 23, 2018, View Source [SID1234530369]).

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Conference Call & Webcast:
Wednesday, November 7, 2018 @ 8:00 am Eastern time
Toll-Free: (844) 882-7834
International: (574) 990-9707
Passcode: 6967538
Webcast: View Source;

Replay available through November 14, 2018
Toll-Free: (855) 859-2056
Replay Passcode: 6967538
The live conference call can also be accessed through a link on the Investor Relations section of Aptose’s website at ir.aptose.com. Please log onto the webcast at least 10 minutes prior to the start of the call to ensure time for any software downloads that may be required. An archived version of the webcast along with a transcript will be available on the company’s website for 30 days.

The press release, the financial statements and the management’s discussion and analysis for the quarter ended September 30, 2018 will be available on SEDAR at www.sedar.com and EDGAR at www.sec.gov/edgar.shtml

On October 23, 2018 Ophthotech Corporation (Nasdaq:OPHT) reported that it will report its third quarter 2018 financial and operating results on Wednesday, October 31, 2018 (Press release, Ophthotech, OCT 23, 2018, View Source [SID1234530059]). Following the announcement, Ophthotech’s management team will host a live conference call and webcast at 8:00 a.m. Eastern Time to discuss the Company’s financial results and provide a general business update.

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To participate in this conference call, dial 888-204-4368 (USA) or 323-994-2082 (International), passcode 3714524. A live, listen-only audio webcast of the conference call can be accessed on the Investor Relations section of the Ophthotech website at: www.ophthotech.com. A replay will be available approximately two hours following the live call for two weeks. The replay number is 888-203-1112 (USA Toll Free), passcode 3714524.

On October 23, 2018 CStone Pharmaceuticals ("CStone") reported that the United States Food and Drug Administration (FDA) has recently granted approval to the company’s Investigational New Drug (IND) application for the independently developed recombinant humanized anti-programmed death-1 (PD-1) monoclonal antibody (mAb) CS1003 (Press release, CStone Pharmaceauticals, OCT 23, 2018, View Source [SID1234530075]). This represents CStone’s second drug candidate to receive IND approval from the FDA less than one month after US clinical trial approval for CS1001 (PD-L1), and demonstrates CStone’s global clinical development capability.

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"Since May this year, CS1003 has now quickly received clinical trial approvals in Australia, China, and the United States, indicating that there are high expectations behind the product itself," said Dr. Frank Jiang, Chairman and CEO of CStone. "I hope that in the future CS1003 can play a key role within combination cancer drug therapies."

CS1003 is a full-length, humanized immunoglobulin G4 (IgG4) anti-PD-1 monoclonal antibody that has shown a good tolerability and efficacy profile in preclinical in vivo studies. The forthcoming clinical trial in the United States extends the Phase I study that began in Australia in May this year to US research centers, and will determine the recommended Phase II dose (RP2D) for CS1003 in solid tumor patients.

Dr. Jason Yang, CStone’s Chief Medical Officer commented: "PD-1 and PD-L1 immunotherapy have been shown to produce strong therapeutic effects in various cancers both as single agents or in combination with multiple cancer therapeutics. CS1003 is a key pipeline candidate for CStone and is currently progressing smoothly through Phase I trial in Australia. We will continue to push forward CS1003’s development in China and around the world to provide patients with a new treatment option at the earliest opportunity."

About CS1003 and the PD-1/PD-L1 pathway

PD-1, or programmed death-1, is an inhibitory checkpoint receptor expressed on T cells. Under normal circumstances, it binds with its ligands, programmed death ligand-1 or ligand 2 (PD-L1/PD-L2), inhibiting T cell and cytokine activation, serving to dampen the immune response in order to prevent damage to healthy tissues. However, studies have shown that PD-L1 can be abundantly expressed on the surface of many solid tumors as well as hematological malignancies. Cancer cells can therefore make use of the PD-1/PD-L1 pathway to successfully avoid immune system recognition. Targeting of the PD-1/PD-L1 checkpoint by anti-tumor drugs can block the "tumor immune evasion mechanism" and restore anti-cancer immune ability in patients.

Unlike other anti-PD-1 mAbs, CS1003 recognizes both human and murine PD-1, providing a unique competitive advantage during efficacy testing in syngeneic mouse tumor models particularly for development of effective combination therapies.