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Bayer Receives EU Approval for Stivarga® (Regorafenib) for the Second-Line Systemic Treatment of Liver Cancer (for specialized target groups only)

On August 7, 2017 Bayer reported the European Commission (EC) has granted marketing authorization for Stivarga (regorafenib) for the treatment of adult patients with HCC who have been previously treated with Nexavar (sorafenib) (Press release, Bayer, AUG 7, 2017, View Source [SID1234520056]). Stivarga is the first and only treatment that has demonstrated a significant improvement in overall survival (OS) in second-line HCC. This marks the third major approval in five months for Stivarga, with the product also gaining approval in the U.S. and Japan for second-line treatment of HCC in April and June, respectively.

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"Until now, there was no effective second-line systemic treatment option for liver cancer patients and their treating physicians in Europe. With the EU approval of Stivarga in HCC, the outlook could significantly improve for patients with HCC, as they have now for the first time, a treatment plan with two approved therapies involving the use of Stivarga directly after Nexavar," said Dr. Jordi Bruix, lead investigator for the RESORCE trial, BCLC Group, Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS, CIBEREHD, Spain.

The approval is based on data from the international, multicenter, placebo-controlled Phase III RESORCE [REgorafenib after SORafenib in patients with hepatoCEllular carcinoma; NCT 01774344] trial, which investigated patients with HCC whose disease had progressed during treatment with Nexavar. In the trial, regorafenib plus best supportive care (BSC) was shown to provide a statistically significant and clinically meaningful improvement in OS versus placebo plus BSC (10.6 vs. 7.8 months, respectively, (HR 0.63; 95% CI 0.50-0.79; p<0.0001)), which translates to a 37% reduction in the risk of death over the trial period. Adverse events observed in the RESORCE trial were generally consistent with the known safety profile of regorafenib. The most common treatment-emergent adverse events were hand-foot skin reaction, diarrhea, fatigue and hypertension.

"Liver cancer is often diagnosed late and difficult to treat, but the EU approval of Stivarga for HCC marks the first treatment advance for patients in nearly a decade. Bayer continues to support the liver cancer community and is committed to ongoing research in the field, as well as continuing to pursue additional regulatory filings for Stivarga across the world," said Robert LaCaze, Executive Vice President and Head of the Oncology Strategic Business Unit at Bayer.

Liver cancer is often more difficult to treat than other cancers with an annual mortality rate of 48,000 in the EU. Globally, it is the second leading cause of cancer-related deaths.

Additional regulatory filings for Stivarga in HCC are under review in other countries around the world, including China. The product was approved in the U.S. and Japan for second-line treatment of HCC in April and June, respectively. Stivarga is already approved in more than 90 countries worldwide, including the U.S., Japan, China and countries in the EU, for the treatment of metastatic colorectal cancer. Stivarga is also approved in more than 80 countries globally, including the U.S., Japan, China and countries in the EU, for the treatment of metastatic gastrointestinal stromal tumors.

About Hepatocellular Carcinoma
Hepatocellular carcinoma, or HCC, is the most common form of liver cancer representing approximately 70-85 percent of liver cancer worldwide. Liver cancer is the sixth most common cancer in the world and the second leading cause of cancer-related deaths globally. More than 780,000 cases of liver cancer are diagnosed worldwide each year (52,000 in the European Union, 501,000 in the Western Pacific region and 30,000 in the United States) and the incidence rate is increasing. In 2012, approximately 746,000 people died of liver cancer including approximately 48,000 in the European Union, 477,000 in the Western Pacific region and 24,000 in the United States.

About Regorafenib (Stivarga)
Regorafenib is an oral multi-kinase inhibitor that potently blocks multiple protein kinases involved in tumor angiogenesis (VEGFR1, -2, -3, TIE2), oncogenesis (KIT, RET, RAF-1, BRAF), metastasis (VEGFR3, PDGFR, FGFR) and tumor immunity (CSF1R).

In the EU, Stivarga is indicated as monotherapy for the treatment of adult patients with mCRC who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-based chemotherapy, an anti-VEGF therapy and an anti-EGFR therapy, as well as for the treatment of adult patients with unresectable or metastatic GIST who progressed on or are intolerant to prior treatment with imatinib and sunitinib, and for the treatment of adult patients with HCC who have been previously treated with sorafenib.

Regorafenib is a compound developed by Bayer. In 2011, Bayer entered into an agreement with Onyx, now an Amgen subsidiary, under which Onyx receives a royalty on all global net sales of regorafenib in oncology.

About Oncology at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative cancer treatments. The oncology franchise at Bayer currently includes three oncology products and several other compounds in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways, with the potential to impact the way that cancer is treated.

10-Q – Quarterly report [Sections 13 or 15(d)]

ArQule has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, ArQule, AUG 4, 2017, View Source [SID1234520138]).

10-Q – Quarterly report [Sections 13 or 15(d)]: v

Lixte Biotechnology has filed a 10-Q – Quarterly report [Sections 13 or 15(d)]: v with the U.S. Securities and Exchange Commission (Filing, 10-Q, Lixte Biotechnology, AUG 4, 2017, View Source [SID1234520042]).

ArQule Reports Second Quarter 2017 Financial Results

On August 4, 2017 ArQule, Inc. (Nasdaq: ARQL) reported its financial results for the second quarter of 2017 (Filing, Q2, ArQule, 2017, AUG 4, 2017, View Source [SID1234520137]).

For the quarter ended June 30, 2017, the Company reported a net loss of $7,201,000 or $0.10 per share, compared with a net loss of $5,100,000 or $0.07 per share, for the second quarter of 2016. For the six-month period ended June 30, 2017, the Company reported a net loss of $14,777,000 or $0.21 per share, compared with a net loss of $10,081,000 or $0.15 per share, for the six-month period ended June 30, 2016.

At June 30, 2017, the Company had a total of approximately $31,007,000 in cash, equivalents and marketable securities.

Key Highlights

· Derazantinib (ARQ 087), a pan-FGFR inhibitor, has begun recruiting in a registrational phase 3 trial for FGFR2 fusion positive second-line intrahepatic cholangiocarcinoma (iCCA). Enrollment is planned to commence in the current quarter. In May, compelling data from the phase 1/2 trial in second-line iCCA was presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) meeting highlighting a disease control rate of 83% and an objective response rate of 21%.

· ARQ 531, an orally bioavailable, potent and reversible BTK inhibitor, has been dosed in a phase 1a/b trial. The trial is enrolling patients with B-cell malignancies, including B-cell lymphomas, chronic lymphocytic leukemia, and Waldenstrom’s macroglobulinemia, who are refractory to other therapeutic options, including ibrutinib. Up to 120 patients can be enrolled in the trial. The company also presented preclinical data for ARQ 531 in diffuse large B-cell lymphoma at the Annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) which further strengthens the preclinical package for this molecule.

· ARQ 092, lead AKT inhibitor, has been dosed in a phase 1/2 company-sponsored trial in Overgrowth Diseases with genetic alterations of the PI3K/AKT1 pathway, including PROS (PIK3CA-related Overgrowth Spectrum) and Proteus syndrome. The trial is designed to enroll six patients in a dose escalation cohort as part of the phase 1 portion of the trial. An additional 10 patients will be enrolled in an expansion cohort as part of the phase 2 portion of the trial. The objective of this study is to determine a clinically meaningful endpoint to pursue in a registrational trial.

"We have made significant progress over the past few months by initiating phase 1 trials for ARQ 092 and ARQ 531 with the aim of achieving clinical proof of principle, and we are now poised to initiate a registrational trial with derazantinib," said Paolo Pucci, Chief Executive Officer of ArQule. "We achieved all of our targeted pipeline milestones for the first half of 2017, most notably moving ARQ 531, our BTK inhibitor, into the clinic. We believe ARQ 531 was the first reversible BTK inhibitor to be dosed in patients with B-cell malignancies. With four programs in the clinic, including derazantinib, ARQ 092, ARQ 751, and ARQ 531, we are poised to continue to achieve our goals for 2017."

"Our pipeline achieved two important milestones with the dosing of the first patient in two biomarker driven clinical trials targeting patients in areas of high unmet need," said Dr. Brian Schwartz, M.D., Head of Research and Development and Chief Medical Officer at ArQule. "In the first of these clinical trials, ARQ 531 aims to demonstrate its potential to address a large patient population with B-cell malignancies who become refractory to current therapies. This is a significant emerging clinical need, particularly in C481S-mutant patients. In the second trial, ARQ 092 is now being dosed in Overgrowth Diseases driven by the PI3K/AKT1 mutation targeting a completely unmet clinical need in a patient population comprised of multiple orphan diseases. Both programs have the potential to be transformational and represent well ArQule’s mission to bring life-changing therapies to address unmet medical needs."

Revenues and Expenses

Revenues for the quarter ended June 30, 2017, were zero compared with revenues of $1,072,000 for the quarter ended June 30, 2016. Revenues in the six-months ended June 30, 2017 were zero compared with revenues of $2,299,000 in the six-months ended June 30, 2016. Revenue in the three and six-month periods of 2016 is comprised of revenue from the Daiichi Sankyo tivantinib development agreement and the Kyowa Hakko Kirin exclusive license agreement. No further revenue is anticipated from these agreements.

Research and development expense in the second quarter of 2017 was $4,983,000, compared with $4,337,000 for the second quarter of 2016. Research and development expense increased $0.6 million in the second quarter of 2017 primarily due to higher outsourced preclinical, clinical and product development costs.

Research and development expense in the six-months ended June 30, 2017 was $10,177,000 compared with $8,535,000 in the six-months ended June 30, 2016. The $1.6 million increase in research and development expense in the six-months ended June 30, 2017 was primarily due to higher outsourced preclinical, clinical and product development costs.

General and administrative expense was $1,866,000 in the second quarter of 2017 compared with $1,887,000 in the second quarter 2016.

General and administrative expense was $3,940,000 in the six-months ended June 30, 2017 compared with $3,931,000 in the six-months ended June 30, 2016.

Epizyme Reports Second Quarter 2017 Financial Results and Clinical and Business Progress

On August 4, 2017 Epizyme, Inc. (NASDAQ:EPZM), a clinical-stage biopharmaceutical company creating novel epigenetic therapies, reported operating results for the second quarter 2017 and highlighted recent business and clinical progress (Press release, Epizyme, AUG 4, 2017, View Source [SID1234520030]).

"Our focus throughout 2017 has been on executing important clinical and regulatory milestones across our tazemetostat program to enable us to bring this first-in-class agent to patients as quickly as we can," said Robert Bazemore, president and chief executive officer of Epizyme. "In addition, we have continued to pursue avenues to accelerate patient enrollment in our studies, including the recently established collaboration with US Oncology Research to support recruitment for our NHL study. We are also pleased to have reached key milestones in our solid tumor program, including completing enrollment in both our Phase 2 mesothelioma study and the epithelioid sarcoma cohort in our Phase 2 INI1-negative solid tumor study, and establishing the recommended dose in our Phase 1 study in children. We believe we have a significant opportunity with tazemetostat in hematological malignancies and solid tumors, and look forward to further evaluating its monotherapy and combination potential and engaging with FDA for our NHL program in the second half of the year."

Tazemetostat Clinical Program Updates

In July 2017, Epizyme completed enrollment in the epithelioid sarcoma (ES) cohort of its ongoing, multi-arm Phase 2 study in adult patients with INI1-negative solid tumors. Following the announcement of positive interim data at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and discussion with the U.S. Food and Drug Administration, the company has identified a path to submission for accelerated approval for the treatment of patients with ES, and is targeting the first New Drug Application for tazemetostat in this indication in 2018.
In July 2017, Epizyme announced that the National Cancer Institute (NCI) initiated its Pediatric MATCH study, which will evaluate tazemetostat in one of the study arms as a monotherapy for pediatric patients with certain genetically defined solid tumors or non-Hodgkin lymphoma. This study is part of the company’s Cooperative Research and Development Agreement (CRADA) executed between Epizyme and the NCI.
In July 2017, the company established the recommended dose for tazemetostat in its study of pediatric patients with solid tumors, and initiated the dose-expansion portion of the study.
In June 2017, the company completed enrollment in its ongoing Phase 2 study designed to evaluate tazemetostat as a treatment for adults with mesothelioma characterized by BAP1 loss-of-function. The company expects to report data from this study in 2018.
In June 2017, Epizyme announced that tazemetostat will be evaluated in combination with atezolizumab (TECENTRIQ) in a Phase 1b/2 clinical study of metastatic non-small cell lung cancer as part of MORPHEUS, Genentech’s open-label, multi-center, randomized umbrella study evaluating the efficacy and safety of multiple immunotherapy-based treatment combinations in solid tumors. This study is an expansion of the company’s clinical collaboration with Genentech, a member of the Roche Group, and is expected to begin enrolling patients by the end of the year.
In June 2017, positive interim efficacy data, grouped by EZH2 mutational status, were presented during a plenary session at the International Conference on Malignant Lymphoma (ICML) from the ongoing Phase 2 clinical trial of tazemetostat as a single-agent treatment for relapsed or refractory patients with follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL). Promising clinical activity and durability were observed across all study cohorts, with enhanced efficacy in the EZH2 mutation cohorts. Importantly, tazemetostat continues to demonstrate a favorable safety profile across the clinical development program.

Recent Business Highlights

In August 2017, Epizyme announced a collaboration with US Oncology Research to implement a separate screening protocol in 68 locations in the U.S. (including satellite locations affiliated with primary sites) to identify relapsed or refractory FL and DLBCL patients with tumors bearing EZH2 mutations who may be candidates for enrollment in Epizyme’s ongoing Phase 2 clinical trial. US Oncology Research will direct identified patients to the tazemetostat Phase 2 clinical trial for protocol screening and potential enrollment into the trial. Sites began screening patients in July 2017.
In June 2017, the U.S. FDA granted Orphan Drug designation to tazemetostat for the treatment of patients with soft tissue sarcoma (STS). Orphan Drug designation conveys eligibility for certain development incentives and market exclusivity for STS independent from Epizyme’s intellectual property protection.

Upcoming 2017 Milestones

Epizyme anticipates engaging with the U.S. FDA in the second half of 2017 to review data from its ongoing Phase 2 study in relapsed or refractory patients with NHL and discussing potential registration paths for tazemetostat.
The company plans to begin a clinical study evaluating tazemetostat as a combination agent for the treatment of patients with FL by the end of 2017.
Epizyme plans to announce the next development candidate from its novel, internally discovered pipeline of epigenetic programs by the end of 2017.
Second Quarter 2017 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $193.0 million as of June 30, 2017, as compared to $211.2 million as of March 31, 2017.
Revenue: $10.0 million was recognized in the second quarter of 2017, compared to $0.5 million for the second quarter of 2016. Revenue in the second quarter of 2017 represents a $10.0 million milestone payment from GlaxoSmithKline (GSK) following their initiation of GLP toxicology studies for a first-in-class methyltransferase inhibitor discovered by Epizyme and licensed to GSK.
R&D Expenses: Research and development (R&D) expenses were $27.3 million for the second quarter of 2017, compared to $21.5 million for the second quarter of 2016. The increase is primarily due to the expansion of the tazemetostat clinical development program, as well as increased research activities related to Epizyme’s next potential development candidate and new target families.
G&A Expenses: General and administrative (G&A) expenses were $11.2 million for the second quarter of 2017, compared to $7.4 million for the second quarter of 2016. The increase is primarily due to an increase in commercial-related activities and legal spending to support the company’s growing intellectual property portfolio.
Net Loss: Net loss was $28.0 million for each of the quarters ended June 30, 2017 and June 30, 2016.
2017 Financial Guidance
Epizyme believes, based on its current operating plan, that its cash, cash equivalents and marketable securities of $193.0 million as of June 30, 2017 will be sufficient to fund the Company’s planned operations into at least the third quarter of 2018.

About the Tazemetostat Clinical Trial Program
Tazemetostat, a first-in-class EZH2 inhibitor, is currently being studied as a monotherapy in ongoing Phase 2 programs in both follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) forms of non-Hodgkin lymphoma (NHL); certain molecularly defined solid tumors, including epithelioid sarcoma and other INI1-negative tumors; and mesothelioma and combination studies in DLBCL. Tazemetostat has been granted Fast Track designation by the U.S. Food and Drug Administration for FL regardless of EZH2 mutation status and for DLBCL with EZH2-activating mutations, as well as Orphan Drug designation for soft tissue sarcoma and malignant rhabdoid tumors.