On June 26, 2018 Istari Oncology, Inc., a clinical-stage biotechnology company focused on novel immuno-oncology and immunotherapy platforms for the treatment of glioblastoma and a wide variety of tumors, reported publication of the results of a Phase 1 trial of PVSRIPO in recurrent glioblastoma in The New England Journal of Medicine (NEJM) (Press release, Istari Oncology, JUN 26, 2018, View Source [SID1234527467]). This trial was conducted by The Preston Robert Tisch Brain Tumor Center at Duke.

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In this trial of 61 adult patients, overall survival at 24 and 36 months was 21%, compared to 14% at 24 months, and 4% at 36 months in matched historical controls. Three patients receiving PVSRIPO have survived beyond 60 months.

"The impressive results with PVSRIPO in this trial are the best we have seen to date in patients with recurrent glioblastoma and provide hope for these patients whose typical survival time is less than a year," said Henry S. Friedman, MD, Chief Medical Officer of Istari and James B. Powell, Jr. Professor of Neuro-Oncology and the Division Chief for Neuro-Oncology in The Preston Robert Tisch Brain Tumor Center in the Department of Neurosurgery at Duke. "Based on the observation that the receptor for PVSRIPO, CD155, is present on almost all solid tumors, we look forward to future trials in other cancers, as well as glioblastoma, both alone and in combination with other agents, as we strive to provide hope for these patients as well."

The primary objective of the Phase 1 study was to determine the toxicity profile and Phase 2 dose for intratumoral convection enhanced delivery of PVSRIPO in WHO grade IV malignant glioma (glioblastoma). The secondary objective was to estimate overall survival compared to an historical control group. From May 2012 to May 2017, 61 consecutive adult patients with recurrent WHO grade IV malignant glioma with measurable disease were enrolled in the study that evaluated seven doses. The median overall survival for all 61 PVSRIPO patients was 12.5 months compared to 11.3 months for the matched historical control group. However, the overall survival of PVSRIPO patients reached a plateau beginning at 24 months with 24- and 36-month overall survival of 21%, while the overall survival in the matched historical control continued to decline with 24-month overall survival of 14%, and 36-month overall survival of 4%. Of these survivors, two patients are beyond 70 months, and one patient is beyond 60 months.

Adverse events affecting more than 20% of patients in the dose-expansion phase included headaches (52%), pyramidal tract syndrome (hemiparesis) (50%), seizure (45%), dysphasia (28%), and cognitive disturbance (25%). The NEJM publication is available at View Source

A multi-center Phase 2 trial of PVSRIPO alone and in combination with chemotherapy in adults with recurrent glioblastoma is currently enrolling, with a primary endpoint of 24-month survival. A Phase 1 trial of PVSRIPO in pediatric patients with recurrent glioblastoma is also currently enrolling. For additional information on clinical trials with PVSRIPO, please visit View Source

Positive preclinical data for PVSRIPO has been generated in multiple solid tumor models, both alone and in combination with other agents, including checkpoint inhibitors. Phase 1 trials are currently planned for PVSRIPO in breast carcinoma and melanoma.

About PVSRIPO
PVSRIPO is the Sabin type 1 polio vaccine, genetically modified so it cannot harm or kill normal cells. PVSRIPO is a prototypic oncolytic recombinant polio virus vaccine that recognizes the poliovirus receptor CD155, which is widely expressed in neoplastic cells of all solid tumors except Burkitt’s lymphoma, and in major immune components of the tumor microenvironment. PVSRIPO has been granted Breakthrough Status and Orphan Status by the FDA.

About Glioblastoma
Glioblastoma is the most common and aggressive form of brain cancer, comprising 52% of patients with primary brain tumors. There are approximately 13,000 patients diagnosed with GBM in the United States annually and approximately 18,000 in the European Union. Despite aggressive treatment, survival for newly diagnosed glioblastoma patients is usually less than 20 months, and for patients with recurrence, which occurs in 98% of patients, survival is usually less than 12 months.

On June 26, 2019 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, and CStone Pharmaceuticals, a privately-held biopharmaceutical company devoted to developing a new generation of innovative drugs, reported an exclusive collaboration and license agreement for the development and commercialization of ivosidenib (TIBSOVO; AG-120) in Mainland China, Hong Kong, Macau and Taiwan ("Territory"), either as a monotherapy or in combination with other therapies (Press release, Agios Pharmaceuticals, JUN 26, 2018, View Source [SID1234537653]). Discovered and developed by Agios, ivosidenib is an investigational, first-in-class, oral, targeted inhibitor of the mutant isocitrate dehydrogenase-1 (IDH1) enzyme. CStone Pharmaceuticals will be responsible for conducting the development and commercialization activities for ivosidenib in hematologic and solid tumor indications in the Territory, with an initial focus in acute myeloid leukemia (AML) and cholangiocarcinoma. Agios will retain all rights to ivosidenib in the rest of the world.

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"CStone Pharmaceuticals brings together a highly experienced leadership team and drug development capabilities that will enable us to reach patients with IDH1 mutant cancers in Greater China who could benefit from ivosidenib," said David Schenkein, M.D., chief executive officer at Agios. "In addition to the clinical development activities that CStone will be leading, we also have the opportunity to leverage CStone’s network to expand our ongoing and future global clinical trials of ivosidenib into Greater China."

Subject to the terms of the agreement, Agios will receive an upfront payment of $12 million and will be eligible to receive up to $412 million in milestone payments, of which $147 million are related to development and regulatory events and $265 million to the achievement of certain sales levels. Approximately half of the milestone payments are related to the development and commercialization of ivosidenib in AML, cholangiocarcinoma and other potential indications. The other half are payable only if development and commercialization of ivosidenib in brain cancer indications, including glioma, are pursued as part of the collaboration at a later date. In addition, CStone Pharmaceuticals will pay Agios tiered royalties ranging from the mid to high-teens as a percentage of annual net sales of ivosidenib in the Territory. CStone Pharmaceuticals will be responsible for all costs associated with development and commercialization activities for ivosidenib conducted in the Territory under the agreement.

"We’re very pleased to partner with Agios to advance the global development of ivosidenib, which has clearly demonstrated significant benefit to patients with AML as well as potential utility in other IDH1m cancers," said Frank Jiang, M.D., Ph.D., chief executive officer at CStone Pharmaceuticals. "Given ivosidenib is currently under U.S. FDA priority review for IDH1m relapsed or refractory AML patients, it is the most advanced program in our pipeline. The partnership will also allow us to explore ivosidenib in combination with other products in our portfolio."

About Ivosidenib (TIBSOVO / AG-120)
Ivosidenib is an investigational first-in-class, orally available, selective, potent inhibitor of the mutated IDH1 protein and is a highly targeted investigational medicine for the treatment of patients with cancers that harbor an IDH1 mutation. IDH1 is a metabolic enzyme that is mutated in a wide range of cancers, including acute myeloid leukemia, cholangiocarcinoma and glioma. Ivosidenib is currently under U.S. FDA priority review for IDH1m R/R AML patients with a PDUFA action date of August 21, 2018. The following clinical trials of ivosidenib are ongoing:

Phase 1 trial of ivosidenib or enasidenib in combination with 7+3 in patients with newly diagnosed IDHm AML who are eligible for standard-of-care chemotherapy
Phase 3 AGILE trial of ivosidenib in combination with azacitidine in patients with newly diagnosed IDH1m AML who are not eligible for standard-of-care chemotherapy
Phase 3 ClarIDHy trial of ivosidenib in advanced IDH1m cholangiocarcinoma
Perioperative study comparing ivosidenib and AG-881 in IDH1m low-grade glioma

On June 26, 2018 Allergan plc (NYSE: AGN) reported that it intends to release second quarter 2018 financial results on Thursday, July 26, 2018, prior to the open of U.S. financial markets (Press release, Allergan, JUN 26, 2018, View Source [SID1234527470]).

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Allergan will host a conference call and webcast at 8:30 a.m. Eastern Time on Thursday, July 26, 2018 to discuss its financial results. The dial-in number to access the call is U.S./Canada (877) 251-7980, International (706) 643-1573, and the conference ID is 67781714.

A taped replay of the conference call will also be available beginning approximately two hours after the call’s conclusion, and will remain available through 11:30 p.m. Eastern Time on August 26, 2018. The replay may be accessed by dialing (855) 859-2056 or (404) 537-3406, and entering the conference ID 67781714.

To access the webcast, please visit Allergan’s Investor Relations website at View Source;. A replay of the webcast will also be available on Allergan’s Investor Relations website.

On June 26, 2018 DelMar Pharmaceuticals, Inc. (NASDAQ: DMPI) ("DelMar" or the "Company"), a biopharmaceutical company focused on the development of new cancer therapies, reported the patient enrollment data for its Phase 2 open-label clinical trial of VAL-083 in bevacizumab (Avastin)-naïve recurrent glioblastoma multiforme (rGBM) patients with MGMT-unmethylated status (Press release, DelMar Pharmaceuticals, JUN 26, 2018, View Source [SID1234527471]).

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This trial is being conducted at MD Anderson Cancer Center and as of June 15, 2018, has enrolled 33 of the planned 48 patients. The trial is designed to determine the impact of VAL-083 treatment on overall survival compared to historical reference control.

"We are pleased with the accelerated patient enrollment of our ongoing VAL-083 Phase 2 trial at MD Anderson Cancer Center. Presently, the trial is approximately six months ahead of schedule and based on the trial’s protocol design, we anticipate the primary endpoint of median overall survival to be reached approximately three months after the final patient is enrolled," said Saiid Zarrabian, President and Chief Executive Officer of DelMar.

About VAL-083

VAL-083 (dianhydrogalactitol) is a "first-in-class," DNA-targeting agent that introduces interstrand DNA cross-links at the N7-position of guanine leading to DNA double-strand breaks and cancer cell death. VAL-083 has demonstrated clinical activity against a range of cancers including GBM and ovarian cancer in historical clinical trials sponsored by the U.S. National Cancer Institute ("NCI"). DelMar has demonstrated that VAL-083’s anti-tumor activity is unaffected by common mechanisms of chemoresistance in vitro. Further details regarding these studies can be found at:

View Source

VAL-083 has been granted an orphan drug designation by the U.S. FDA Office of Orphan Products for the treatment of glioma, medulloblastoma and ovarian cancer, and in Europe for the treatment of malignant gliomas. VAL-083 has been granted fast-track status for the treatment of recurrent GBM by the US FDA.

On June 25, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the Phase III IMpower133 study met its co-primary endpoints of overall survival (OS) and progression-free survival (PFS) at its first interim analysis (Press release, Hoffmann-La Roche, JUN 25, 2018, View Source [SID1234527451]). The study demonstrated that initial (first-line) treatment with the combination of TECENTRIQ (atezolizumab) plus chemotherapy (carboplatin and etoposide) helped people with extensive-stage small cell lung cancer (ES-SCLC) live significantly longer compared to chemotherapy alone. The TECENTRIQ-based combination also reduced the risk of disease worsening or death (PFS) compared to chemotherapy alone. Safety for the TECENTRIQ and chemotherapy combination appeared consistent with the known safety profile of the individual medicines, and no new safety signals were identified with the combination. These data will be presented at an upcoming medical meeting.

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"These are the first positive Phase III survival results for any immunotherapy-based combination in the initial treatment of extensive-stage small cell lung cancer, a particularly difficult-to-treat type of disease," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "The clinically meaningful results from the IMpower133 study add to the growing body of evidence demonstrating that TECENTRIQ-based combinations may be an effective treatment for different types of advanced lung cancer. We look forward to working with health authorities globally to bring this potential treatment option to people with this type of disease as soon as possible."

This is the fourth positive Phase III lung cancer study evaluating a TECENTRIQ-based combination to read out this year and the fifth positive study overall. Currently, Roche has eight Phase III lung cancer studies underway evaluating TECENTRIQ alone or in combination with other medicines across different types of lung cancer.

About the IMpower133 study
IMpower133 is a Phase III, multicentre, double-blinded, randomised placebo-controlled study evaluating the efficacy and safety of TECENTRIQ in combination with carboplatin and etoposide versus chemotherapy (carboplatin plus etoposide) alone in chemotherapy-naïve people with ES-SCLC.

The study enrolled 403 people who were randomised equally (1:1) to receive:

TECENTRIQ in combination with carboplatin and etoposide (Arm A), or
Placebo in combination with carboplatin and etoposide (Arm B, control arm)

During the treatment-induction phase, people received treatment on 21-day cycles for four cycles, followed by maintenance with TECENTRIQ or placebo until progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). Treatment could be continued until persistent radiographic PD or symptomatic deterioration was observed.

The co-primary endpoints were:

PFS as determined by the investigator using RECIST v1.1 in the intention-to-treat (ITT) population
OS in the ITT population
IMpower133 met its OS and PFS co-primary endpoints as per the study protocol.

About SCLC
Lung cancer is the leading cause of cancer death globally.1 Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day.1 Lung cancer can be broadly divided into two major types: non-small cell lung cancer (NSCLC) and SCLC, with SCLC accounting for approximately 15% of all lung cancer cases.2 Survival rates for people with SCLC vary depending on the stage (extent) of the cancer at the time of diagnosis.3 The five-year relative survival rate for people with stage I SCLC is approximately 31%, however, at stage IV, the five-year relative survival rate declines to approximately 2%.4

About TECENTRIQ
TECENTRIQ is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, TECENTRIQ may enable the activation of T cells. TECENTRIQ has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.

Currently, Roche has eight Phase III lung cancer studies underway, evaluating TECENTRIQ alone or in combination with other medicines.

TECENTRIQ is already approved in the European Union, United States and more than 70 countries for people with previously treated metastatic NSCLC and for certain types of untreated or previously treated metastatic urothelial carcinoma (mUC).