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Positive Phase 1b Data for NewLink Genetics’ IDO Pathway Inhibitor, Indoximod, in Combination with Chemotherapy for Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) Presented at the European Hematologic Association (EHA) Congress in Madrid, Spain

On June 23, 2017 NewLink Genetics Corporation (NASDAQ:NLNK) reported the presentation of data from the Phase 1b portion of a study of indoximod, an IDO pathway inhibitor, in combination with idarubicin and cytarabine for patients with newly diagnosed acute myeloid leukemia (AML) (Press release, NewLink Genetics, JUN 23, 2017, View Source [SID1234519660]). Abstract E-912, Indoximod in Combination with Idarubicin and Cytarabine for Upfront Treatment of Patients with Newly Diagnosed Acute Myeloid Leukemia (AML): Phase 1 Report, is being presented by Ashkan Emadi, M.D., Ph.D., Associate Professor of Medicine at the University of Maryland Greenebaum Comprehensive Cancer Center, during the European Hematology Association (EHA) (Free EHA Whitepaper) Congress in Madrid, Spain on Friday, June 23, 2017, 9:30 AM to Saturday, June 24, 7:00 PM CET.

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These data indicate indoximod does not appear to add significant toxicity to standard therapy for patients with newly diagnosed AML, and no regimen-limiting toxicities (RLT) have been observed to date. Initial data show that the morphological complete remission (CR) rate is as expected after one cycle of induction chemotherapy. Seven of seven patients who achieved CR were found to have no minimal residual disease (MRD-neg).

"While from a small number of patients, these data show an encouraging MRD negativity rate and may offer the potential for measurable clinical benefits for patients," said Dr. Emadi, Principal Investigator of this study.

About Indoximod
Indoximod is an investigational, orally available small molecule targeting the IDO pathway. The IDO pathway is one of the key immuno-oncology targets involved in regulating the tumor microenvironment and immune escape.

Bellicum Announces Clinical Data on BPX-501 at Presidential Symposium of the 22nd Congress of the European Hematology Association

On June 23, 2017 Bellicum Pharmaceuticals, Inc. (Nasdaq:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, reported that results will be presented today from its global BP-004 clinical trial of BPX-501 in the Presidential Symposium at the 22nd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) being held in Madrid, Spain (Press release, Bellicum Pharmaceuticals, JUN 23, 2017, View Source [SID1234519659]). Clinical results reported in pediatric patients with a wide range of genetic blood diseases and hematologic cancers suggest that BPX-501 lowers the risks associated with haploidentical stem cell transplants, increasing their acceptability for more patients who could benefit but lack a matched donor. The EHA (Free EHA Whitepaper)’s Presidential Symposium showcases the top abstracts selected by the Scientific Program Committee each year.

"The vast majority of patients in this study experienced successful engraftment, no or low grade GvHD, rapid immune recovery and early hospital discharge," said Dr. Franco Locatelli, MD, PhD, Director of the Department of Pediatric Hematology and Oncology, Ospedale Pediatrico Bambino Gesù (OPBG), Rome. "All cases of uncontrolled acute GvHD were resolved by administration of rimiducid to activate the CaspaCIDe safety switch incorporated in BPX-501. With low incidence of transplant-related mortality and manageable GvHD, these data suggest that the addition of BPX-501 T cells could represent a meaningful advance for patients in need of a transplant but who lack a matched related donor."

Updated Results of BP-004 Study in Global and EU Populations

Investigators reported on pediatric patients with hematologic cancers and genetic blood diseases who underwent treatment with BPX-501 after an alpha/beta T-cell depleted haploidentical hematopoietic stem cell transplant (alpha/beta T-cell depleted haplo-HSCT) and had at least six months of follow-up. Investigators reviewed overall data on 98 patients from 12 centers in the U.S. and Europe, as well as on the subset of 61 patients at European sites.

At the 180-day measurement time point, cumulative incidence of transplant-related mortality (TRM) was 5% in the overall patient population. A significant reduction in viral infections and reinfections was observed with BPX-501 compared to results from a study in Rome (OPBG) in patients undergoing an alpha/beta T-cell depleted haplo-HSCT without the addition of BPX-501 (n=107). Additionally, there were no reported adverse events associated with the use of BPX-501 or rimiducid. At six months of follow-up, the cumulative incidence of Grade 2-4 acute Graft versus Host Disease (GvHD) was 13 percent. The cumulative incidence of chronic GvHD was three percent at one year of follow-up.

The administration of rimiducid was required in 11 patients with acute GvHD who did not respond to standard treatments. In all 11 cases, rimiducid rapidly resolved the GvHD. In addition, the non-reactive T cells recovered, with no recurrence of GvHD.

Data from the subset of 61 patients from European sites were also reviewed in the presentation. At six months of follow-up there was no transplant-related mortality. Cumulative GvHD incidence remains low, with incidence rates of 10 percent for Grade 2-4 acute GvHD, and three percent for Grade 3-4 acute GvHD. There was no persistent chronic GvHD.

"Data from our global BP-004 study continue to show consistent and strong overall outcomes across a wide range of diseases, suggesting the potential to enable curative stem cell transplants from partially matched donors for more children," said Rick Fair, President and CEO of Bellicum Pharmaceuticals. "Data from this ongoing BP-004 study in Europe, along with comparative data from an observational trial of pediatric patients undergoing a stem cell transplant from matched unrelated donors, are expected to support the filing of a European Marketing Authorization Application in mid-2018."

Patient Populations Included in Study, By Disease Type

Genetic Blood Diseases (n=59) Hematologic Cancers (n=39)
Primary immune deficiencies (n=26) Acute lymphoblastic leukemia (ALL) (n=21)
Thalassemia major (n=8) Acute myeloid leukemia (AML) (n=14)
Hemophagocytic lymphohistiocytosis (HLH) (n=6) Other (n=4)
Sickle cell disease (n=5)
Other (n=14)

Hemoglobinopathies and Erythroid Disorders Poster Presentation
Also today at the 22nd Congress of EHA (Free EHA Whitepaper), updated results will be presented in patients with hemoglobinopathies and erythroid disorders, including five patients with sickle cell disease, in a poster presentation titled: "The Use of BPX-501 Donor T-Cell Infusion (with Inducible Caspase 9 Suicide Gene) Together with HLA-Haploidentical Stem Cell Transplant to Treat Children with Hemoglobinopathies and Erythroid Disorders."

All 15 patients in the cohort showed normal hemoglobin levels and remained transfusion-free at 180 days, with no transplant-related mortality.

The Presidential Symposium oral presentation (abstract S146) will take place today, June 23 at 3:45 – 4:00 PM CEST (9:45-10:00 AM EDT) and the poster (abstract P381) will be reviewed today at 5:15 – 6:45 PM CEST (11:15 AM – 12:45 PM EDT). Both presentations will be made available in the Events and Presentations section of the Bellicum website shortly after the time of the respective presentation.

About BPX-501
BPX-501 is an adjunct T-cell therapy administered after allogeneic HSCT, comprising genetically modified donor T cells incorporating Bellicum’s CaspaCIDe safety switch. It is designed to provide a safety net to eliminate alloreactive BPX-501 T cells (via administration of activator agent rimiducid) should uncontrollable GvHD occur. This enables physicians to more safely perform stem cell transplants by administering BPX-501 engineered T cells to speed immune reconstitution, provide control over viral infections and enhance Graft-versus-leukemia effect, without unacceptable GvHD risk. The ongoing BP-004 clinical study of BPX-501 is being conducted at transplant centers in the U.S. and Europe.

Bayer Receives Positive CHMP Opinion for regorafenib for the Second-Line Systemic Treatment of Liver Cancer (for specialized target groups only)

On June 23, 2017 Bayer reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has recommended regorafenib for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with Nexavar (sorafenib) (Press release, Bayer, JUN 23, 2017, View Source [SID1234519658]). Regorafenib is the first and only treatment that has demonstrated a significant improvement in overall survival in second-line HCC patients who previously had no other options. The final decision of the European Commission on the marketing authorization is expected in the coming months. The anti-cancer medication from Bayer is already approved under the brand name Stivarga in more than 90 countries worldwide for the treatment of metastatic colorectal cancer (CRC), including countries of the EU, and in more than 80 countries globally for the treatment of metastatic gastrointestinal stromal tumors (GIST), including countries of the EU. The product recently gained approval in the U.S. for second-line treatment of HCC and additional regulatory filings for Stivarga in HCC are under review in countries around the world, including China.

"Liver cancer is one of the leading cancer-related causes of death in Europe. Nexavar, as the first and only approved systemic treatment for HCC, has been a major advance in this field, but effective second-line treatment options are urgently needed for patients," said Robert LaCaze, Executive Vice President and Head of the Oncology Strategic Business Unit at Bayer. "The positive opinion for regorafenib in Europe is great news for patients as it supports our efforts to make this treatment available to as many patients as possible in the second-line HCC setting and offers a treatment plan with two therapies that both have shown to improve overall survival."

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

The positive opinion 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 overall survival (OS) versus placebo plus BSC (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. The median OS was 10.6 vs. 7.8 months for regorafenib and the placebo groups, respectively. Adverse events observed in the trial were generally consistent with the known safety profile of regorafenib. The most common treatment-emergent adverse events (regorafenib vs. placebo group) were hand–foot skin reaction (53% vs. 8%), diarrhea (41% vs. 15%), fatigue (40% vs. 32%) and hypertension (31% vs. 6%).

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).

Regorafenib is approved under the brand name Stivarga in more than 90 countries worldwide, including the U.S., countries of the EU, China and Japan for the treatment of metastatic colorectal cancer (mCRC). The product is also approved in over 80 countries, including the U.S., countries of the EU, China and Japan, for the treatment of metastatic gastrointestinal stromal tumors (GIST). It was recently approved in the U.S. for second-line treatment of HCC. Additional regulatory filings for Stivarga in HCC are under review in countries around the world, including China.

In the EU, Stivarga is indicated 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.

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.

AVEO Oncology Announces Positive CHMP Opinion for Tivozanib as a Treatment of Advanced Renal Cell Carcinoma

On June 23, 2017 AVEO Oncology (NASDAQ:AVEO) reported that the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMA), has recommended FOTIVDA (tivozanib) for approval as a treatment for patients with advanced renal cell carcinoma (RCC) (Press release, AVEO, JUN 23, 2017, View Source [SID1234519657]). The CHMP’s recommendation is now referred to the European Commission (EC). The EC, which typically adheres to the recommendation of the CHMP, but is not obligated to do so, is expected to make its final decision in about 67 days. If approved by the EC, marketing authorization for tivozanib will be granted in all 28 countries of the European Union, Norway, Iceland and Liechtenstein. EUSA Pharma, a specialty pharmaceutical company with a focus on oncology and oncology supportive care, is the European licensee for tivozanib.

"A positive opinion from the CHMP is a critical step in our goal of obtaining regulatory approval of tivozanib as a treatment for RCC," said Michael Bailey, president and chief executive officer of AVEO. "Tivozanib’s unique tolerability profile together with the longest progression free survival reported in a Phase 3 first line RCC study, have the potential to fill an unmet patient need for better tolerated treatment in this disease. Further, we believe this tolerability profile could enable immune-oncology combinations such as those in the Phase 1/2 TiNivo study, which combines the PD-1 inhibitor Opdivo (nivolumab) with tivozanib and recently advanced to Phase 2."

Mr. Bailey concluded: "If the European Commission grants marketing approval for tivozanib, it would trigger a $4 million research and development reimbursement payment from EUSA, and AVEO will also be eligible for up to $12 million in additional milestones from EUSA based on member state reimbursement and regulatory approvals. These payments would add significant resources to our balance sheet as we work toward the anticipated readout of our U.S. pivotal trial in third-line RCC, the TIVO-3 trial, in the first quarter of 2018."

Under the terms of their December 2015 agreement, EUSA Pharma has agreed to pay AVEO up to $394 million in future research and development funding and milestone payments, assuming successful achievement of specified development, regulatory and commercialization objectives, as well as a tiered royalty ranging from a low double-digit up to mid-twenty percent on net sales of tivozanib in the agreement’s territories. Thirty percent of milestone and royalty payments received by AVEO, excluding research and development funding, are due to Kyowa Hakko Kirin (KHK) as a sublicensing fee in Europe. In the United States, the royalty obligation to KHK ranges from the low- to mid-teens on net sales.

RCC is the most common form of kidney cancer,i which accounts for an estimated 49,000 deaths in Europe each year.ii It is expected to be one of the fastest increasing cancers over the next ten years.iii Tyrosine Kinase Inhibitor (TKI) vascular endothelial growth factor (VEGF) inhibitors are the standard of care treatment for advanced RCC in Europe, however, patients on current treatments can often experience significant side effects.iv,v If approved for use in the European Union, tivozanib would be indicated for use in adult patients with advanced RCC who are VEGFR and mTOR pathway inhibitor-naïve and are either untreated or who have failed prior therapy with interferon-alpha (IFN-α) or interleukin-2 (IL-2).

About Tivozanib

Tivozanib is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI). It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications. Tivozanib has been investigated in several tumors types, including renal cell, colorectal and breast cancers.

Faslodex (fulvestrant) receives positive CHMP opinion for use in 1st-line hormone receptor-positive advanced breast cancer

On June 23, 2017 AstraZeneca reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion, recommending the marketing authorisation of Faslodex (fulvestrant) for the treatment of hormone receptor-positive (HR+), locally-advanced or metastatic breast cancer in postmenopausal women not previously treated with endocrine therapy, or with disease relapse on or after adjuvant anti-oestrogen therapy, or disease progression on anti-oestrogen therapy (Press release, AstraZeneca, JUN 23, 2017, View Source [SID1234519656]).

The CHMP recommendation is based on pivotal data from the Phase III FALCON trial, where Faslodex 500mg demonstrated superiority over anastrozole 1mg in the treatment of locally-advanced or metastatic breast cancer in post-menopausal women who had not received prior hormonal-based medicine for HR+ breast cancer.

The FALCON data show that the delay in disease worsening or death (median progression-free survival, PFS) was 2.8 months longer with Faslodex than anastrozole. The median PFS was 16.6 months in the Faslodex arm compared with 13.8 months in the anastrozole arm. Aromatase inhibitors such as anastrozole are the current standard of care for the 1st-line treatment for postmenopausal women with HR+ advanced breast cancer.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "Faslodex has long been an effective medicine for women with advanced breast cancer in later lines of treatment and we are pleased that the CHMP has recognised its potential as a first-line option. Faslodex is also being tested in combination with over 19 different medicines, which is testament to its well-established safety and efficacy profile with over 15 years of patient evidence since its first launch in 2002."

The safety and tolerability profile was in line with current experience with Faslodex and anastrozole. The most-commonly reported adverse events (AEs) in the Faslodex and anastrozole arms were arthralgia (16.7% vs. 10.3%), hot flush (11.4% vs. 10.3%) and nausea (10.5% vs. 10.3%).

Faslodex is the only hormone medicine for advanced breast cancer that slows tumour growth by binding to and degrading the oestrogen receptor – a key driver of breast cancer progression in some women. It is widely approved for the treatment of HR+ advanced breast cancer in postmenopausal women with disease progression following anti-oestrogen medicine.

The CHMP’s positive opinion will now be reviewed by the European Commission, which has the authority to approve medicines for the European Union (EU). The final decision will be applicable to all 28 EU member countries plus Iceland, Norway and Liechtenstein.

NOTES TO EDITORS

About FALCON

The FALCON (Fulvestrant and AnastrozoLe COmpared in hormonal therapy-Naïve advanced breast cancer) trial is a Phase III, randomised, double-blind, multicentre trial comparing the antitumour effects and tolerability profile of a 500mg dose of Faslodex plus placebo with a 1mg dose of anastrozole plus placebo, in postmenopausal women with HR+, locally-advanced or metastatic breast cancer who have not been treated previously with any hormonal medicine.

The FALCON trial was designed on the basis of positive results from the Phase II FIRST trial, which demonstrated a median overall survival nearly six months longer with Faslodex compared to anastrozole.

About Advanced Breast Cancer

Advanced/metastatic breast cancer refers to Stage III and IV breast cancer. Stage III disease may also be referred to as locally-advanced breast cancer, while metastatic disease is the most-advanced stage of breast cancer (Stage IV), and occurs when cancer cells have spread beyond the initial tumour site to other organs of the body outside the breast. Since there is no cure for the disease, the goal of current treatment is to delay disease worsening or death.

About Faslodex

Faslodex (fulvestrant) is indicated for the treatment of postmenopausal women with oestrogen receptor-positive (ER+), locally-advanced or metastatic breast cancer with disease relapse on or after adjuvant anti-oestrogen treatment, or disease progression on treatment with an antioestrogen.

In the US, Faslodex is also approved, in combination with palbociclib, for the treatment of women with HR+, HER2-negative advanced or metastatic breast cancer, whose cancer has progressed after endocrine medicine. Faslodex represents a hormonal treatment approach that helps to slow tumour growth by blocking and degrading the oestrogen receptor – a key driver of disease progression.

About 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 at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s five Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody-Drug Conjugates – 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.