On January 16, 2018 Transgene (Paris:TNG) (Euronext Paris: TNG), a biotechnology company that designs and develops virus-based immunotherapies, reported the dosing of the first patient in the Phase 2 trial evaluating TG4010 in combination with Opdivo (nivolumab) and chemotherapy as a first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC) with low or no expression of PD-L1 by the tumor cells (Press release, Transgene, JAN 16, 2018, View Source [SID1234523195]).

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The Phase 2 clinical trial is exploring the tolerability and efficacy of the combination regimen of Transgene’s TG4010, an investigational active immunotherapy against MUC1 tumor-associated antigen, with Bristol-Myers Squibb’s immune checkpoint inhibitor, Opdivo (nivolumab), which acts by overcoming immune suppression, and standard platinum doublet chemotherapy.
This multi-center single-arm trial will enroll up to 39 patients (without EGFR activating mutations or ALK-rearrangements), both in the USA and Europe. The trial has objective tumor responses rate (ORR) as primary endpoint. The study will also assess the safety and tolerability of the regimen together with other efficacy and immunological parameters. The first results are expected in H2 2018.
More information on the trial can be found on clinicaltrial.gov (NCT03353675).
This trial is conducted by Transgene under a clinical collaboration agreement with Bristol-Myers Squibb, which is supplying nivolumab (see press release dated April 25, 2017).

"Advanced lung cancer remains a devastating disease, in particular for patients whose tumors express low or undetectable levels of PD-L1. We are excited to start a trial that combines our active immunotherapy TG4010, with nivolumab and chemotherapy as a first-line treatment" said Maud Brandely, Chief Medical Officer of Transgene. "We believe that this trial could confirm the promising efficacy data that we previously obtained with TG4010 in combination with chemotherapy, and show that the triple regimen could be an attractive treatment option in this patient population."

Elisabeth Quoix, M.D., Head of the Department of Pulmonology at the University Hospital of Strasbourg, and coordinating investigator of the trial, added: "The three complementary mechanisms of action of TG4010, nivolumab and chemotherapy are believed to enhance the immune cellular response and lead to an increase in antitumor activity. This combination regimen aims at achieving a higher response rate, and ultimately an improvement in the survival rate in advanced-stage NSCLC patients."

The combination of TG4010 immunotherapy and chemotherapy has demonstrated significant efficacy in terms of increased response rate, progression-free survival and overall survival in a randomized, double-blind, placebo-controlled Phase 2b trial in first-line treatment of patients with advanced non-squamous NSCLC (Quoix et al. Lancet Oncol. 2015).

About TG4010
TG4010 is an active immunotherapy that has been designed to express the coding sequences of the MUC1 tumor-associated antigen and the cytokine, Interleukin-2 (IL2). It is based on a modified Vaccinia virus (MVA), and has been shown to induce an immune response against MUC1 expressing tumors, such as non-small cell lung cancer (NSCLC). Its mechanism of action and excellent safety profile make TG4010 a very suitable candidate for combinations with other therapies, including immune checkpoint inhibitors and chemotherapy. The combination of TG4010 immunotherapy and chemotherapy has demonstrated significant efficacy in terms of progression-free survival and overall survival in patients with advanced stage NSCLC (Quoix et al. Lancet Oncol. 2015).
TG4010 is being investigated in combination with nivolumab (ICI) for the 2nd-line treatment of advanced NSCLC (NCT02823990) and for 1st-line treatment of NSCLC in combination with nivolumab and chemotherapy in patients whose tumors express low or undetectable levels of PD-L1 (NCT03353675).

About Non-Small Cell Lung Cancer
Lung cancer is one of the most common malignancies worldwide with an estimated 1.8 million new cases annually. It is also a leading cause of cancer-related deaths, accounting for an estimated 1.6 million deaths in 2012 (Source: GLOBOCAN 2012). Advanced lung cancer remains one of the cancer types with the worst prognosis (five-year survival rate for advanced NSCLC of less than 5%), underlining the still unmet need in this disease despite recent progress.

On January 16, 2018 Athenex, Inc. (Nasdaq:ATNX), a global biopharmaceutical company dedicated to the discovery, development and commercialization of novel therapies for the treatment of cancer and related conditions, reported that the United States Food and Drug Administration ("FDA") has provided positive feedback on the design of the currently ongoing Phase III Clinical Trial for Oraxol, an innovative oral formulation of paclitaxel combined with HM30181A (a novel P-gp inhibitor) (Press release, Athenex, JAN 16, 2018, View Source;p=RssLanding&cat=news&id=2326701 [SID1234523137]). Specifically, the FDA indicated that if the study meets the primary endpoint with an acceptable Benefit/Risk profile, it could be adequate as a single comparative trial to support registration of Oraxol for a metastatic breast cancer indication in the United States.

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The Oraxol Phase III clinical study (KX-ORAX-001) is a randomized controlled international clinical trial investigating the superiority of Oraxol over intravenous ("IV") paclitaxel in the treatment of patients with metastatic breast cancer. The primary endpoint is confirmed tumor response rate assessed by a blinded independent radiologic imaging analysis center using the RECIST Criteria, a generally accepted clinical response criteria for efficacy in tumor reduction. The study has a target sample size of 360 patients. The study has completed the first of two planned interim analyses. The second interim analysis based on 180 evaluable patients is planned for the middle of 2018. The positive US FDA feedback would allow an Oraxol US registration submission upon successful completion of this single Phase III study.

Dr. Rudolf Kwan, Athenex’s Chief Medical Officer, commented, "This positive feedback from the U.S. FDA is an important step in bringing Oraxol closer to the doctors and patients. Our Phase III trial also recently received the unanimous recommendation to continue by an independent Data and Safety Monitoring Board. The recommendation was based on the positive overall response rate of Oraxol and the very low incidence of neuropathy, which is a severe dose-limiting side-effect of IV paclitaxel."

Dr. Johnson Lau, Athenex’s Chief Executive Officer, added, "We are delighted with the positive feedback from the FDA on the Phase III Clinical Study Design for Oraxol, which provides further validation of our regulatory pathway for Oraxol. With the recent allowance of the Oraxol Investigational New Drug application in China and the receipt of the Promising Innovative Medicine designation from the United Kingdom Medicines and Healthcare products Regulatory Agency, we continue to advance towards our goal of improving the lives of cancer patients worldwide."

Athenex previously announced that the Data and Safety Monitoring Board unanimously recommended the continuation of its Phase III clinical trial comparing Oraxol versus IV paclitaxel in the treatment of metastatic breast cancer after the interim analysis of the first 90 patients on October 5, 2017. Additionally, the Company announced the receipt of the Promising Innovative Medicine designation for Oraxol by the United Kingdom Medicines and Healthcare products Regulatory Agency on December 27, 2017, qualifying Athenex to apply for Step II of the Early Access to Medicines Scheme to provide patients early access to Oraxol prior to receiving marketing authorization. Athenex also recently announced that the Chinese FDA has allowed the Investigational New Drug application for Oraxol on January 8, 2018, enabling Athenex to initiate clinical studies in China.

On January 6, 2018 Context Therapeutics, a biopharma company dedicated to developing new medicines for patients with hormone responsive cancers, reported that it has acquired worldwide rights to Apristor (Onapristone XR) (Press release, Context Therapeutics, JAN 16, 2018, View Source [SID1234523265]). Onapristone has been extensively studied and has established efficacy in two Phase 2 metastatic breast cancer clinical trials. In these trials, meaningful clinical benefit and response rates were seen in 120 metastatic breast cancer patients, 101 of whom were actively progressing on Tamoxifen before Onapristone treatment initiation. Onapristone has been studied in over 200 patients, and it was well tolerated with no drug-related serious adverse events.

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Martin Lehr, CEO of Context stated: "We are excited to advance the development of Apristor and to potentially provide a mechanistically novel option for patients diagnosed with metastatic breast cancer. Unfortunately, the median life expectancy of a woman diagnosed with metastatic breast cancer is approximately three years. In the United States alone 40,000 women die each year as a result. These women deserve better, and we are committed to improving their treatment and removing the fear that comes along with this diagnosis."

Apristor blocks the binding of progesterone, a carcinogen, to the progesterone receptor (PR). Up to 70% of metastatic breast cancers express PR and are said to be PR+. If approved, Apristor would provide physicians with a novel product that could be used in combination with standard of care agents targeting the estrogen receptor or as a monotherapy.

Context made a one-time payment to Arno Therapeutics in exchange for the worldwide rights to Apristor. Apristor is a new chemical entity and is protected by a robust patent estate that should provide exclusivity through at least 2034.

Scott Applebaum, President of Context stated: "Context has taken a big leap forward and is now a clinical-stage company. This transformation is consistent with our mission of discovering, developing, and commercializing treatments for hormone-responsive cancers. We are building a world-class global clinical trial organization to bring Apristor to market as fast as possible. In addition, we have an Apristor fast-follower program for progesterone receptor-mediated diseases and continue to advance our preclinical Sigma1 program."

On January 16, 2018 Constellation Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company developing tumor-targeted and immuno-oncology therapies based on its pioneering research and development in cancer epigenetics, reported it has initiated a Phase 1b/2 clinical trial to evaluate CPI-1205, a small-molecule inhibitor of Enhancer of Zeste Homolog 2 (EZH2), combined with checkpoint inhibitor ipilimumab (marketed as YERVOY by Bristol-Myers Squibb) and potentially other cancer immunotherapies (Press release, Constellation Pharmaceuticals, JAN 16, 2018, View Source [SID1234523138]). The study, named ORIOn-E, is based on translational insights which identified combination approaches using epigenetics-mediated mechanisms aimed at Overcoming Resistance to Immune Oncology therapies by inhibiting EZH2.

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"This is the second combination study we’ve initiated evaluating the potential for CPI-1205 to overcome resistance mechanisms to existing cancer therapies," said Jigar Raythatha, president and chief executive officer of Constellation Pharmaceuticals. "Our preclinical results with CPI-1205 demonstrate that epigenetic targets can be utilized by cancers to suppress the immune system and render immunotherapy treatment options less effective. We aim to build on this insight with CPI-1205 in clinical trials and with other epigenetic therapies that we discover and develop in this important area of research."

CPI-1205 is a potent, highly selective, first-generation small-molecule inhibitor of an enzyme called EZH2. In pre-clinical studies, CPI-1205 has shown potential to re-wire T regulatory and T effector cells within tumors to enhance tumor rejection alone and synergistically in combination with immune checkpoint inhibition.

"Since they were first made available in the U.S., checkpoint inhibitor therapies like ipilimumab have provided considerable benefit for patients with many different cancers. However, many patients do not respond to therapy or relapse after initial response," said Adrian Senderowicz, M.D., senior vice president and chief medical officer of Constellation Pharmaceuticals. "CPI-1205 plays a critical role in inhibiting the suppressive function of regulatory T cells and consequently may address resistance mechanisms that limit the benefit of immune checkpoint inhibitors in patients."

The Phase 1b portion is a dose escalation study designed to evaluate the safety, pharmacokinetics, pharmacodynamics and the assessment of potential predictive biomarkers in patients across solid tumors when treated with CPI-1205 in combination with ipilimumab. The Phase 2 portion will be conducted in melanoma patients, among other cancers.

About CPI-1205
CPI-1205 is a therapeutic candidate from Constellation Pharmaceuticals’ EZH2 portfolio and is an inhibitor of Enhancer of Zeste Homolog 2 (EZH2). The function of EZH2 is to selectively suppress gene expression of several pro-cancer pathways that contribute to drug resistance.

On January 16, 2018 Foundation Medicine, Inc. (NASDAQ:FMI) reported that the company has entered into a broad partnership with Pfizer Inc. (NYSE: PFE)(Press release, Foundation Medicine, JAN 16, 2018, View Source [SID1234523141]) . The partnership focuses on development, regulatory support and commercialization of companion diagnostics (CDx) that will be included in updates to FoundationOne CDx. FoundationOne CDx is Foundation Medicine’s FDA-approved comprehensive genomic profiling (CGP) assay for all solid tumors that incorporates multiple companion diagnostics. Pfizer will also benefit from access to FoundationInsights, Foundation Medicine’s data analytics platform, to facilitate novel biomarker discovery and to optimize clinical trial design. The unique combination of FoundationInsights and FoundationOne CDx will potentially enable Pfizer to leverage Foundation Medicine’s platform technology to accelerate discovery and development of precision oncology therapeutics.

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Pfizer currently has 10 FDA-approved oncology medicines that treat a diverse array of solid tumors and hematologic malignancies. In addition, its oncology pipeline includes 17 assets in clinical development and 19 phase 3 studies.

"Our mission to transform cancer care includes partnering with biopharma companies to expedite development of personalized treatment options for patients. We are proud to partner with Pfizer who shares our commitment to precision oncology and biomarker-driven drug development," said Melanie Nallicheri, chief business officer and head of biopharma at Foundation Medicine. "The combination of our FDA-approved comprehensive genomic profiling platform and molecular information solutions, coupled with Pfizer’s robust oncology portfolio, enables us to enhance the impact of precision oncology to advance patient care."

FoundationOne CDx assesses all classes of genomic alterations in 324 genes known to drive cancer growth, providing potentially actionable information to help guide treatment decisions. It also reports genomic biomarkers, such as microsatellite instability (MSI) and tumor mutational burden (TMB), that can help inform the use of immunotherapies; genomic alterations in other genes relevant to patient management; and relevant clinical trial information. As such, it is designed to help streamline companion diagnostic development, mitigate risk and advance targeted therapy development. Currently FoundationOne CDx is FDA-approved as a CGP assay for all solid tumors and a broad companion diagnostic for patients with certain types of non-small cell lung cancer, melanoma, colorectal cancer, ovarian cancer or breast cancer to identify those patients who may benefit from treatment with one of 17 on-label targeted therapies.

Concurrent with FDA approval, the Centers for Medicare & Medicaid Services (CMS) issued a preliminary National Coverage Determination (NCD) for FoundationOne CDx. The draft NCD would provide coverage for FDA-approved companion diagnostic claims, as well as a pathway for additional coverage with evidence development in other solid tumor types. The final policy is expected to issue during the first quarter of 2018 following public comment on the preliminary NCD and an administrative period.