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VBL Therapeutics Announces Data Safety Monitoring Committee Provides Green Light to Advance the OVAL Phase 3 Registration Enabling Study of VB-111 in Ovarian Cancer

On February 22, 2021 VBL Therapeutics (Nasdaq: VBLT) reported the results of the independent Data Safety Monitoring Committee (DSMC) pre-planned review of the ongoing OVAL Phase 3 registration enabling study of VB-111 in recurrent ovarian cancer (Press release, VBL Therapeutics, FEB 22, 2021, View Source [SID1234575357]). The committee found no safety issues with the trial and recommended its continuation as planned.

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"This review continues the trend of encouraging reviews that have taken place since the clinical trial began," said Prof. Dror Harats, Chief Executive Officer of VBL Therapeutics. "The trial continues to enroll on track in the US, Europe and Israel. We look forward to the next DSMC review during the third quarter of 2021, followed by completion of enrollment at the end of 2021 or in early 2022."

In March 2020, the Company announced results of the first interim analysis in the OVAL study, which reviewed unblinded data and assessed CA-125 response, measured according to the GCIG criteria, in the first 60 enrolled subjects evaluable for CA-125 analysis. The overall response rate across both arms was 53%. The response rate in the treatment arm (VB-111 in addition to weekly paclitaxel) was at least 10% higher than in the control, i.e., 58% or higher. In patients who had post-dosing fever, which is a marker for VB-111 treatment, the response rate was 69%. According to the Company update on November 16, 2020, a high response rate of >50% in the total evaluable patient population was maintained with approximately 200 patients enrolled.

About the OVAL study (NCT03398655)
OVAL is an international Phase 3 randomized pivotal registration enabling clinical trial that compares a combination of VB-111 and paclitaxel to placebo plus paclitaxel, in patients with platinum-resistant ovarian cancer. The study is planned to enroll 400 patients. OVAL is conducted in collaboration with the GOG Foundation, Inc., an independent international non-profit organization with the purpose of promoting excellence in the quality and integrity of clinical and basic scientific research in the field of gynecologic malignancies.

About VB-111 (ofranergene obadenovec)
VB-111 is an investigational first-in-class, targeted anti-cancer gene-therapy agent that is being developed to treat a wide range of solid tumors. VB-111 is a unique biologic agent that uses a dual mechanism to target solid tumors. Its mechanism combines blockade of tumor vasculature with an anti-tumor immune response. VB-111 is administered as an IV infusion once every 6-8 weeks. It has been observed to be well-tolerated in >300 cancer patients and demonstrated activity signals in an "all comers" Phase 1 trial as well as in three tumor-specific Phase 2 studies. VB-111 has received an Orphan Designation for the treatment of ovarian cancer from the European Commission. VB-111 has also received orphan drug designation in both the US and Europe, and fast track designation in the US for prolongation of survival in patients with rGBM. VB-111 successfully demonstrated proof-of-concept and survival benefit in Phase 2 clinical trials in radioiodine-refractory thyroid cancer and recurrent platinum-resistant ovarian cancer.

ChromaDex Announces $25 Million Private Placement of Common Stock

On February 22, 2021 ChromaDex Corp. (NASDAQ: CDXC) reported that it has entered into a securities purchase agreement for the sale of $25.0 million of its common stock in a private placement (Press release, ChromaDex, FEB 22, 2021, View Source [SID1234575356]). The private placement was led by a new international investor and is expected to close on or about February 23, 2021, subject to the satisfaction of customary closing conditions. In connection with the investment, the Company agreed to sell 3,846,153 shares of its common stock at a per share price of $6.50, for gross proceeds of approximately $25.0 million.

The net proceeds from the private placement are expected to provide ChromaDex with added resources to accelerate growth of the Tru Niagen global brand, advance clinical research on NAD+ precursors, and support general corporate purposes.

The shares of common stock being sold in the private placement will not have been registered under the Securities Act of 1933, as amended (the "Act"). Accordingly, such shares may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements under the Act. In connection with the private placement, ChromaDex expects to enter into a registration rights agreement with the investors. Additional details about the transaction are included in a Current Report on Form 8-K filed by ChromaDex concurrently with this release. This press release does not constitute an offer to sell or the solicitation of an offer to buy the securities, nor shall there be any sale of the securities in any state in which such offer or sale would be unlawful prior to the registration or qualification under the securities laws of such state. Any offering of the securities under the resale registration statement will only be by means of a prospectus.

"With this additional capital, we intend to further our position as the world’s leading NAD+ company with expanded scientific research on nicotinamide riboside (NR) and other NAD+ precursors," says ChromaDex CEO Rob Fried. "We will also expand our marketing efforts on our flagship consumer brand, Tru Niagen, the safest and most efficient way to boost NAD+ levels, while continuing to protect our intellectual property against infringers. We are honored to have EverFund as an investor who sees the significant opportunity for Niagen globally."

New Positive Data from Can-Fite’s Liver Cancer Phase II Clinical Study with Namodenoson

On February 22, 2021 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE:CFBI), a biotechnology company with a pipeline of proprietary small molecule drugs that address inflammatory, cancer and liver diseases, reported new data from the Phase II advanced liver cancer study including overall survival of nearly 4 years in two patients who are under namodenoson treatment (Press release, Can-Fite BioPharma, FEB 22, 2021, View Source [SID1234575355]). Additional findings show disappearance of ascites, normal liver function and good quality of life. In one patient stable disease has been recorded with disappearance of peritoneal carcinomatosis. Namodenoson continues to demonstrate a good safety profile and is well tolerated with no severe adverse events reported.

Recently, the Company successfully concluded End-of-Phase II meetings with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA). Both agencies agreed with Can-Fite’s proposed pivotal Phase III trial design of Namodenoson for the treatment of patients with advanced hepatocellular carcinoma (HCC), with underlying Child Pugh B7 (CPB7) cirrhosis to support a New Drug Application (NDA) submission and approval. The trial is expected to enroll 450 patients through multiple centers worldwide. Namodenoson has Orphan Drug Designation for HCC in the U.S. and Europe, has Fast Track Status in the U.S., and is currently treating liver cancer patients through a compassionate use program in Israel.

"We are very pleased to see prolonged survival, good quality of life, and in particular clearance of peritoneal carcinomas in these two patients. The FDA and EMA gave a green light to one pivotal Phase III study which, upon positive conclusion, would lead to registration of Namodenoson for the treatment of this devastating disease. To our knowledge, Can Fite is the only company developing a drug for this advanced patient population defined as Child Pugh B7 (CPB7) cirrhosis," stated Can-Fite CEO Dr. Pnina Fishman.

About Namodenoson

Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson was evaluated in Phase II trials for two indications, as a second line treatment for hepatocellular carcinoma, and as a treatment for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug.

Voluntary withdrawal of Imfinzi indication in advanced bladder cancer in the US

On February 22, 2021 AstraZeneca reported the voluntary withdrawal of the Imfinzi (durvalumab) indication in the US for previously treated adult patients with locally advanced or metastatic bladder cancer (Press release, AstraZeneca, FEB 22, 2021, View Source [SID1234575353]). This decision was made in consultation with the Food and Drug Administration (FDA).

In May 2017, Imfinzi was granted accelerated approval in the US based on promising tumour response rates and duration of response data from Study 1108, a Phase I/II trial that evaluated the safety and efficacy of Imfinzi in advanced solid tumours, including previously treated bladder cancer. Continued approval was contingent on results from the DANUBE Phase III trial in the 1st-line metastatic bladder cancer setting, which did not meet its primary endpoints in 2020. The withdrawal is aligned with FDA guidance for evaluating indications with accelerated approvals that did not meet post-marketing requirements, as part of a broader industry-wide evaluation. This withdrawal does not impact the indication outside the US and does not impact other approved Imfinzi indications within or outside the US.

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "The science of immunotherapy has moved swiftly over the past few years, bringing new options to patients at an unprecedented pace. While the withdrawal in previously treated metastatic bladder cancer is disappointing, we respect the principles FDA set out when the accelerated approval pathway was founded and remain committed to bringing new and innovative options to patients. In the last three years, Imfinzi has become an important standard of care in multiple lung cancer settings, an area of considerable focus for AstraZeneca."

Healthcare providers are being notified of this update. Patients with metastatic bladder cancer currently being treated with Imfinzi should consult with their healthcare provider regarding their ongoing care.

Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is approved in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) after chemoradiation therapy in the US, Japan, China, across the EU and in many other countries, based on the PACIFIC Phase III trial. Imfinzi is also approved in the EU, US, Japan and many other countries around the world for the treatment of extensive stage small cell lung cancer (ES-SCLC) based on the CASPIAN Phase III trial. Imfinzi is also approved for previously treated patients with advanced bladder cancer in several countries.

As part of a broad development programme, Imfinzi is being tested as a monotherapy and in combinations including with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, SCLC, bladder cancer, liver cancer, biliary tract cancer, oesophageal cancer, gastric and gastroesophageal cancer, cervical cancer, ovarian cancer, endometrial cancer, and other solid tumours.

In bladder cancer, the Company has several Phase III trials testing Imfinzi in various treatment combinations across early- and late-stage settings including the NILE Phase III trial in metastatic disease, the NIAGARA Phase III trial in muscle invasive disease and the POTOMAC Phase III trial in non-muscle invasive disease.

AstraZeneca in immunotherapy
Immunotherapy is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. The Company’s IO portfolio is anchored in immunotherapies that have been designed to overcome anti-tumour immune suppression. AstraZeneca is invested in using IO approaches that deliver long-term survival for new groups of patients across tumour types.

The Company is pursuing a comprehensive clinical-trial programme that includes Imfinzi as a monotherapy and in combination with tremelimumab in multiple tumour types, stages of disease, and lines of therapy, and where relevant using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine the IO portfolio with radiation, chemotherapy, small, targeted molecules from across AstraZeneca’s oncology pipeline, and from research partners, may provide new treatment options across a broad range of tumours.

AstraZeneca in oncology
AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

By harnessing the power of six scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.

MHLW GRANTS ORPHAN DRUG DESIGNATION IN JAPAN TO NOVEL FIBROBLAST GROWTH FACTOR (FGF) RECEPTOR SELECTIVE TYROSINE KINASE INHIBITOR E7090 WITH PROSPECTIVE INDICATION FOR UNRESECTABLE BILIARY TRACT CANCER WITH FGFR2 GENE FUSION

On February 22, 2021 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that it has received orphan drug designation for a prospective indication for unresectable biliary tract cancer with FGFR2 gene fusion by the Ministry of Health, Labour and Welfare, Japan (MHLW) for its in-house discovered fibroblast growth factor (FGF) receptor (FGFR1, FGFR2, FGFR3) selective tyrosine kinase inhibitor E7090, which is currently under development as an orally available novel anti-cancer agent (Press release, Eisai, FEB 22, 2021, View Source [SID1234575351]).

FGFRs with genetic aberrations are known to play an important role in the proliferation, survival and migration of cancer cells as well as tumor angiogenesis and drug resistance. These genetic aberrations in FGFRs have been observed in various types of cancers, therefore, there is growing interest in FGFRs as a promising target for cancer therapy. By selectively inhibiting FGFR1, 2 and 3, and blocking those signals, E7090 has the potential to become a new molecular targeted therapy for cancers with FGFR genetic aberrations.

In Japan, a Phase I clinical trial of E7090 was conducted, and E7090 has been designated as the target drug for the SAKIGAKE Designation System of the MHLW for the treatment of unresectable biliary tract cancer. Currently, a Phase II clinical trial (Study 201) of E7090 is underway in patients with cholangiocarcinoma with FGFR2 gene fusion in Japan and China.

Eisai positions oncology as a key therapeutic area and is aiming to discover innovative new medicines with the potential to cure cancer. Eisai is committed to exploring the potential clinical benefits of E7090 for cancer treatment, as it seeks to contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer and their families.

Discovered in-house by Eisai’s Tsukuba Research Laboratories, E7090 is an orally available novel tyrosine kinase inhibitor that demonstrates selective inhibitory activity against fibroblast growth factor receptors (FGFR) FGFR1, FGFR2 and FGFR3. Distinct from prior known FGFR inhibitors, E7090 has a basic structure which lacks the dimethoxyphenyl moiety, and in a kinetic interaction analysis study, it was observed that E7090 demonstrates antitumor effects due to inhibition of kinase activity with a binding mode (Type V) that exhibits rapid and potent binding as well as high selectivity to FGFR.1

A Phase II clinical trial (Study 201) of E7090 is underway in Japan and China to evaluate efficacy and safety in patients with cholangiocarcinoma with FGFR2 gene fusion. A Phase I clinical trial of E7090 is also underway in Japan in patients with estrogen receptor-positive and HER2-negative breast cancer.

2. About Biliary Tract Cancer with FGFR2 Gene Fusion
The five-year survival rate for biliary tract cancer is approximately 20%, which makes it an intractable cancer with the second worst prognosis following pancreatic cancer.2 Drug therapy options are limited in comparison with other cancers, and as such it is a disease with significant unmet medical needs. The estimated number of patients with biliary tract cancer is approximately 32,000 in Japan.3,4,5 FGFR2 gene fusion is observed in approximately 14% of intrahepatic cholangiocarcinoma, which account for 15-30% of biliary tract cancers.6

3. Orphan Drug Designation System in Japan
The orphan drug designation system in Japan aims to support the development of drugs for diseases for which the number of patients is small and research and development is not progressing, despite high unmet medical need. As the requirement for designation based on Article 77-2 of the Pharmaceutical and Medical Device Act (PMD Act) of Japan, a drug must meet the following conditions in order to be considered for orphan drug designation in Japan: the number of people expected to use the drug for its intended use is less than 50,000 people in Japan; there is no suitable alternative drug or treatments in Japan, or the proposed drug is expected to be significantly more effective or safer than drugs already available on the Japanese market; and there is a scientific rationale to support the necessity of the drug for the target disease, and the development plan for the drug is appropriate. Specific measures to support the development of orphan drugs include giving prioritized consultation regarding clinical development and conducting priority examinations, reducing application fees, extending registration validity period, granting subsidies for research and development expenditures, and tax incentives.
1 Watanabe Miyano S. et al., "E7090, a Novel Selective Inhibitor of Fibroblast Growth Factor Receptors, Displays Potent Antitumor Activity and Prolongs Survival in Preclinical Models", Molecular Cancer Therapeutics, 2016, 15(11), 2630-2639.

2 Latest statistics, Cancer Information Service, National Cancer Center, Japan.

3 Official Statics of Japan (e-Stat), 2017 Patient Survey View Source(New Window)

4 The 21st Follow-up Survey Reports for Primary Liver Cancer Cases in Japan (2010-2011), 2020.

5 Shin Ishihara. et al., "Biliary tract cancer registry in Japan from 2008 to 2013", J Hepatobiliary Pancreat Sci., 2016, 23, 149-157.

6 Arai Y. et al., "Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma", Hepatology, 2014, 59, 1427-1434.