On December 7, 2015 Amgen (NASDAQ:AMGN) reported that new data from three Phase 2 trials support the efficacy and safety of BLINCYTO (blinatumomab) in adults with acute lymphoblastic leukemia (ALL) (Press release, Amgen, DEC 7, 2015, View Source;p=RssLanding&cat=news&id=2120598 [SID:1234508458]). These data were presented today in oral sessions at the 57th Annual Meeting and Exposition of the American Society of Hematology (ASH) (Free ASH Whitepaper) in Orlando, Fla.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Infographic – Understanding Minimal Residual Disease (MRD)

In a Phase 2 confirmatory multicenter single-arm trial (BLAST), adult patients with B-cell precursor ALL with minimal residual disease (MRD) who received BLINCYTO monotherapy demonstrated clinically meaningful relapse-free survival (RFS), as measured in the key secondary endpoint (abstract #680). Median RFS was 18.9 months following initiation of BLINCYTO. MRD refers to the presence of leukemia blast cells below the limits of detection available with standard assessment. Results from the Phase 2 BLAST trial were nominated for inclusion in the Best of ASH (Free ASH Whitepaper) Session on Tuesday, Dec. 8 from 11:30 a.m. – 1 p.m. ET.

Other presentations demonstrate BLINCYTO’s potential in a high risk subpopulation of patients with relapsed or refractory Philadelphia chromosome-positive (Ph+) B-precursor ALL (abstract #679) and confirm BLINCYTO’s efficacy in a subset of patients with relapsed or refractory Philadelphia chromosome-negative (Ph-) ALL after an allogeneic hematopoietic stem cell transplantation (alloHSCT), who typically have poor outcomes with current therapies (abstract #861).

"A key goal in the treatment of blood cancers is to prevent relapse from occurring," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Achieving a complete minimal residual disease, or MRD response, is important because having no detectable MRD places ALL patients at a lower risk for relapse when compared to patients with persistent or recurrent MRD. The data presented are highly encouraging because they support the potential of BLINCYTO in a broader spectrum of ALL patients, including those at an earlier stage of disease."

ALL is a rare and rapidly progressing cancer of the blood and bone marrow.1,2 In adult patients with relapsed or refractory ALL, median overall survival (OS) is just three to five months.3 Currently, there is no broadly accepted standard treatment regimen for adult patients with relapsed or refractory ALL beyond chemotherapy.4 Around 15-30 percent of adult ALL patients are Ph+ and these patients typically have a poor response to standard therapy, short remission duration and low survival rates.5

Abstracts are currently available on the ASH (Free ASH Whitepaper) website.

ASH Abstract #680: Long-Term Outcomes After Blinatumomab Treatment: Follow-up of a Phase 2 Study in Patients With Minimal Residual Disease (MRD) Positive B-cell Precursor ALL

In this long-term follow up from the Phase 2 ‘203 study of 116 patients with B-precursor ALL and persistent or recurrent MRD after first-line chemotherapy, patients who achieved an MRD complete response with BLINCYTO had a longer OS, RFS and duration of remission (DOR) compared with those not achieving an MRD complete response, with a median OS in MRD-negative patients of 40.4 months. In data reported at ASH (Free ASH Whitepaper) 2014, treatment with BLINCYTO resulted in complete MRD response in cycle 1 in 78 percent of patients.
The most clinically relevant adverse events (AEs) were neurologic events, including tremor (30 percent), aphasia (13 percent), dizziness (8 percent), ataxia and paresthesia (6 percent each), and encephalopathy (5 percent). Rates decreased over time (cycles 1, 2, 3 and 4) for any neurologic event (47 percent, 24 percent, 15 percent and 15 percent) and any grade 3 or higher neurologic event (10 percent, 4 percent, 0 percent and 0 percent).
ASH Abstract #679: Complete Molecular and Hematologic Response in Adult Patients with Relapsed/Refractory (R/R) Philadelphia Chromosome-Positive B-Precursor Acute Lymphoblastic Leukemia (ALL) Following Treatment with Blinatumomab: Results from a Phase 2 Single-Arm, Multicenter Study (ALCANTARA)

In the Phase 2 ALCANTARA study, BLINCYTO showed antileukemic activity in very poor prognosis patients with relapsed or refractory Ph+ B-precursor ALL after failure of at least one second-generation tyrosine kinase inhibitor (TKI) therapy, with 36 percent of patients achieving complete remission or complete remission with partial hematological recovery (CR/CRh) during the first two treatment cycles. Of patients who achieved CR/CRh, 88 percent achieved a complete MRD response. Equivalent response rates were observed in patients with kinase-domain mutations in BCR-ABL such as T315I (four achieved CR/CRh; all four also achieved a complete MRD response).
Patient incidence of grade 3 or higher treatment-emergent AEs was 82 percent, most commonly febrile neutropenia (27 percent), thrombocytopenia (22 percent), anemia (16 percent), pyrexia (11 percent) and neurologic events (7 percent). There were no episodes of grade 3 or higher cytokine release syndrome.
ASH Abstract #861: Treatment with anti-CD19 BiTE Blinatumomab in Adult Patients with Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r ALL) Post-Allogeneic Hematopoietic Stem Cell Transplantation

In this analysis from the pivotal Phase 2 ‘211 trial, BLINCYTO induced a CR/CRh rate of 45 percent in a subset of 64 heavily pretreated patients with Ph- ALL who had relapsed or were refractory after an alloHSCT.
In total, 88 percent of patients had grade 3 or higher treatment-emergent AEs, with the most frequent including neutropenia (22 percent), febrile neutropenia (20 percent), anemia (17 percent) and thrombocytopenia (14 percent). Six patients reported treatment-emergent graft vs. host disease (GvHD), two of which were grade 3 or higher.
Amgen Webcast Investor Meeting

Amgen will host a webcast investor meeting at ASH (Free ASH Whitepaper) on Monday, Dec. 7, 2015, at 7 p.m. ET. Sean E. Harper, M.D., executive vice president of Research and Development at Amgen, along with members of Amgen’s clinical development team and clinical investigators will participate to discuss data presented at ASH (Free ASH Whitepaper) and Amgen’s broader oncology portfolio of products.

Live audio of the conference call will be simultaneously broadcast over the Internet and will be available to members of the news media, investors and the general public.

The webcast, as with other selected presentations regarding developments in Amgen’s business given by management at certain investor and medical conferences, can be found on Amgen’s website, www.amgen.com under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen’s Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.

About BLINCYTO (blinatumomab)

BLINCYTO is a bispecific CD19-directed CD3 T cell engager (BiTE) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells. BLINCYTO was granted breakthrough therapy and priority review designations by the U.S. Food and Drug Administration, and is now approved in the U.S. for the treatment of Ph- relapsed or refractory B-cell precursor ALL. This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.

About BiTE Technology

BiTE antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the body’s immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE antibody constructs are currently being investigated for their potential to treat a wide variety of cancers.

BLINCYTO U.S. Product Safety Information

Important Safety Information Regarding BLINCYTO (blinatumomab) U.S. Indication
This safety information is specific to the current U.S. approved indication.

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES

Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended.
Neurological toxicities, which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended.
Contraindications

BLINCYTO is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.

Warnings and Precautions

Cytokine Release Syndrome (CRS): Life-threatening or fatal CRS occurred in patients receiving BLINCYTO. Infusion reactions have occurred and may be clinically indistinguishable from manifestations of CRS. Closely monitor patients for signs and symptoms of serious events such as pyrexia, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), disseminated intravascular coagulation (DIC), capillary leak syndrome (CLS), and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Interrupt or discontinue BLINCYTO as outlined in the Prescribing Information (PI).

Neurological Toxicities: Approximately 50% of patients receiving BLINCYTO in clinical trials experienced neurological toxicities. Severe, life-threatening, or fatal neurological toxicities occurred in approximately 15% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. The median time to onset of any neurological toxicity was 7 days. Monitor patients for signs or symptoms and interrupt or discontinue BLINCYTO as outlined in the PI.

Infections: Approximately 25% of patients receiving BLINCYTO experienced serious infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO as needed.

Tumor Lysis Syndrome (TLS): Life-threatening or fatal TLS has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on treatment hydration, should be used during BLINCYTO treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO as needed to manage these events.

Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters during BLINCYTO infusion and interrupt BLINCYTO if prolonged neutropenia occurs.

Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures, patients receiving BLINCYTO are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO is being administered.

Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO treatment. The majority of these events were observed in the setting of CRS. The median time to onset was 15 days. Grade 3 or greater elevations in liver enzymes occurred in 6% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase (GGT), and TBILI prior to the start of and during BLINCYTO treatment. BLINCYTO treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if TBILI rises to > 3 times ULN.

Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO, especially in patients previously treated with cranial irradiation and anti-leukemic chemotherapy. Preparation and administration errors have occurred with BLINCYTO treatment. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).

Adverse Reactions

The most commonly reported adverse reactions (≥ 20%) in clinical trials were pyrexia (62%), headache (36%), peripheral edema (25%), febrile neutropenia (25%), nausea (25%), hypokalemia (23%), rash (21%), tremor (20%), diarrhea (20%) and constipation (20%).

Serious adverse reactions were reported in 65% of patients. The most common serious adverse reactions (≥ 2%) included febrile neutropenia, pyrexia, pneumonia, sepsis, neutropenia, device-related infection, tremor, encephalopathy, infection, overdose, confusion, Staphylococcal bacteremia, and headache.

U.S. Dosage and Administration Guidelines

BLINCYTO is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which should be programmable, lockable, non-elastomeric, and have an alarm. It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).

Please see full U.S. Prescribing Information and medication guide for BLINCYTO at www.BLINCYTO.com.

On December 07, 2015 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported the enrollment of the first patient in the INSPIRE trial for IV rigosertib as a treatment for higher-risk myelodysplastic syndromes (HR-MDS) after failure of hypomethylating agent (HMA) therapy (Press release, Onconova, DEC 7, 2015, View Source [SID:1234508457]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"There is a significant unmet medical need in patients who have failed treatment with an HMA, the only available therapy for HR-MDS," said Dr. Guillermo Garcia-Manero, lead investigator for the INSPIRE trial and Chief of the Section of Myelodysplastic Syndromes at The University of Texas MD Anderson Cancer Center. "In previous clinical studies, rigosertib demonstrated positive results in HR-MDS patients with very poor prognosis. The INSPIRE trial is designed to assess the effects of IV rigosertib in these HR-MDS patients who have a short life-span and no effective therapies currently available."

The INSPIRE trial is a global, multi-center, randomized controlled study to assess the efficacy and safety of IV rigosertib in HR-MDS patients under 80 years of age who had progressed on, or failed to respond to, or relapse after previous treatment with HMAs. The trial will enroll approximately 225 patients randomized at a 2:1 ratio into two treatment arms: IV rigosertib plus Best Supportive Care versus Physician’s Choice plus Best Supportive Care. The primary endpoint of INSPIRE is overall survival and an interim analysis is anticipated.

Clinical Trial Applications (CTAs) and/or site initiation activities for INSPIRE have begun in several European countries, Australia and Israel. Onconova’s collaboration partner in Japan and Korea, SymBio Pharmaceuticals, Ltd., will enroll patients in Japan. In addition, Baxalta Incorporated (BXLT), Onconova’s commercialization partner in Europe, is providing financial support for the trial, up to a specified cap.

About Rigosertib

Rigosertib is a small molecule that inhibits cellular signaling by acting as a Ras mimetic. This is believed to be mediated by direct binding of rigosertib to the Ras-binding domain (RBD) found in many Ras effector proteins, including the Raf kinases and PI3K. The initial therapeutic focus for rigosertib is myelodysplastic syndromes (MDS), a group of bone marrow disorders characterized by ineffective formation of blood cells that often converts into acute myeloid leukemia (AML). Clinical trials for rigosertib are being conducted at leading institutions in the United States, Europe, and the Asia-Pacific region. Rigosertib is protected by issued patents (earliest expiry in 2026) and has been awarded Orphan Designation for MDS in the United States, Europe and Japan.

About INSPIRE

The INternational Study of Phase III IV RigosErtib, or INSPIRE, is based on guidance received from the U.S. Food and Drug Administration and European Medicines Agency and derives from the findings of the ONTIME Phase 3 trial. INSPIRE is a multi-center, randomized controlled study to assess the efficacy and safety of IV rigosertib in HR-MDS patients under 80 years of age who had progressed on, or failed to respond to, or relapse after previous treatment with HMAs within the first nine months of initiation of HMA treatment. The trial will enroll approximately 225 patients randomized at a 2:1 ratio into two treatment arms: IV rigosertib plus Best Supportive Care versus Physician’s Choice plus Best Supportive Care. The primary endpoint of INSPIRE is overall survival and an interim analysis is anticipated. Full details of the INSPIRE trial, such as inclusion and exclusion criteria, as well as secondary endpoints, can be found on clinicaltrials.gov (NCT02562443).

On December 7, 2015 MEI Pharma, Inc. (Nasdaq: MEIP), an oncology company focused on the clinical development of novel therapies for cancer, reported positive results from a Phase II study of its investigational drug candidate Pracinostat in combination with azacitidine (marketed as Vidaza) in elderly patients with newly diagnosed acute myeloid leukemia (AML) (Press release, MEI Pharma, DEC 7, 2015, View Source [SID:1234508456]). The results were presented earlier today at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando. A copy of the presentation is now available at www.meipharma.com.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

According to the oral presentation by principal investigator Dr. Guillermo Garcia-Manero, MD Anderson Cancer Center, 28 of the 50 patients in the study (56%) achieved the primary endpoint of complete response (CR) plus complete response with incomplete blood count recovery (CRi) plus morphologic leukemia-free state (MLFS), including 21 patients (42%) who achieved a CR. Notably, 19 of the 21 patients who achieved a CR are still alive with a 100% one-year survival rate among all CR patients, indicating a correlation between CR and survival with this low intensity therapy.

Median overall survival for all 50 patients in the study has not been reached, with 28 patients still living and a median observation time of 14.3 months. These data compare favorably to a recent international Phase III study of azacitidine (AZA-001)1, which showed a median overall survival of 10.4 months with azacitidine alone and a CR rate of 19.5% in a similar patient population. Median survival among patients with high-risk cytogenetics in this study (n=21) was 13.3 months, more than double the median survival of the high-risk population in the AZA-001 study (6.4 months).

"These are impressive results by virtually any measure for a group of patients in dire need of effective new treatment options," said Dr. Garcia-Manero. "Not only did we observe a high rate of responses, but many occurred rapidly and continued to improve with ongoing therapy. Most importantly, we are seeing an encouraging trend in overall survival, particularly among patients who achieved a complete response. These data clearly support further development of Pracinostat in combination with azacitidine for the treatment of elderly patients with AML."

The open-label study enrolled a total of 50 patients at 15 centers across the U.S. Median age in the study was 76 years. Patients received 60 mg of Pracinostat orally three times a week for three weeks followed by one week of rest and 75 mg m2 of azacitidine via subcutaneous injection or intravenous infusion for the first seven days of each 28-day cycle. The combination of Pracinostat and azacitidine was generally well tolerated in the study, with no unexpected toxicities. The most common grade 3/4 treatment-emergent adverse events reported in >10% of all patients included febrile neutropenia, thrombocytopenia, anemia and fatigue.

"We are very excited about our growing body of AML data, which continues to exceed expectations and guide us forward with the development of this program," said Daniel P. Gold, Ph.D., President and Chief Executive Officer of MEI Pharma. "Over the past several months we have learned that our randomized study of Pracinostat and azacitidine in myelodysplastic syndrome (MDS) was hindered by a high rate of discontinuations due to adverse events, but appeared to show a benefit for patients who were able to tolerate treatment for at least four cycles compared to azacitidine alone. The results from our AML study demonstrate that many patients are achieving responses within the first two cycles, with fewer discontinuations overall due to adverse events compared to our MDS study, suggesting a prudent development path forward for the combination.

"Based on these findings," continued Dr. Gold, "we will now begin to prepare for a Phase III registration study of Pracinostat and azacitidine in elderly patients with newly diagnosed AML, which we plan to initiate in the second half of 2016. We look forward to sharing more information regarding the design of this study in the months ahead."

About Pracinostat

Pracinostat is a potent oral inhibitor of a group of enzymes called histone deacetylases, or HDACs. HDACs belong to a larger set of proteins collectively known as epigenetic regulators that can alter gene expression by chemically modifying DNA or its associated chromosomal proteins. Abnormal activity of these regulators is believed to play an important role in cancer and other diseases. Pracinostat has been tested in multiple Phase I and Phase II clinical studies in advanced hematologic diseases and solid tumor indications. The results of these studies suggest that Pracinostat has potential best-in-class pharmacokinetic properties when compared to other oral HDAC inhibitors, with side effects often associated with drugs of this class, including fatigue and myelofibrosis. Pracinostat has not been approved for commercial distribution in the U.S.

MEI Pharma owns exclusive worldwide rights to Pracinostat.

About AML

Acute myeloid leukemia (also known as acute myelogenous leukemia) is the most common acute leukemia affecting adults, and its incidence is expected to continue to increase as the population ages. The American Cancer Society estimates about 20,830 new cases of AML per year in the U.S., with an average age of about 67 years. Treatment options for AML remain virtually unchanged over the past 30 years. Front line treatment consists primarily of chemotherapy, while the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology recommend azacitidine or decitabine (marketed as Dacogen) as low intensity treatment options for AML patients over the age of 60 who are unsuitable for induction chemotherapy.

On December 7, 2015 ImmunoCellular Therapeutics, Ltd. ("ImmunoCellular") (NYSE MKT: IMUC) reported the establishment of an agreement with a major cancer research group, Alliance Foundation Trials, LLC (AFT), for the phase 3 registrational trial of its cancer immunotherapy ICT-107 in patients with newly diagnosed glioblastoma (Press release, ImmunoCellular Therapeutics, DEC 7, 2015, View Source [SID:1234508455]). AFT in conjunction with the Alliance for Clinical Trials in Oncology comprises nearly 10,000 cancer specialists at hospitals, medical centers, and community clinics across the United States. AFT will support the phase 3 trial by providing access to its large network of clinical sites and patients, with the goal of accelerating patient enrollment in the trial. Multiple phase 3 clinical trial sites have been opened for patient enrollment in the US, with additional sites anticipated to open in Canada and Europe in the coming weeks and months.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Andrew Gengos, ImmunoCellular Chief Executive Officer, commented: "Working in collaboration with AFT has the potential to significantly accelerate enrollment in the ICT-107 phase 3 trial, and to engage the participation of important clinical sites throughout in the US. AFT is one of the most highly respected cancer organizations in America, and we are appreciative of their endorsement and support for our registrational trial."

ImmunoCellular has reached agreement with the FDA on a Special Protocol Assessment (SPA) with respect to the primary and secondary endpoints as well as the statistical plan for the phase 3 trial. ImmunoCellular has also been awarded a $19.9 million grant from the governing Board of the California Institute for Regenerative Medicine (CIRM), California’s stem cell agency, to implement the phase 3 registration trial.

On December 7, 2015 Epizyme, Inc. (NASDAQ:EPZM), a clinical stage biopharmaceutical company creating novel epigenetic therapeutics for cancer patients, reported updated results from the ongoing phase 1 trial of tazemetostat (EPZ-6438), a first-in-class oral EZH2 inhibitor (Press release, Epizyme, DEC 7, 2015, View Source [SID:1234508454]). Data from this trial continue to show meaningful clinical activity with tazemetostat when used as an oral monotherapy in patients with either relapsed or refractory Non-Hodgkin Lymphoma (NHL). Nine of 16 response-evaluable patients with NHL have achieved an objective response, with the duration of responses lasting up to 19 months as of the data cutoff. The data were presented today by Vincent Ribrag, M.D., Institut Gustave Roussy, at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (ASH) (Free ASH Whitepaper).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"In this ongoing phase 1 study, we continue to observe meaningful and durable clinical activity with tazemetostat in NHL patients," said Dr. Ribrag. "The phase 2 five-arm study, which is currently underway, will advance our understanding of the clinical utility of this agent in the different subsets of NHL. I believe tazemetostat has the potential to become an important new addition to the available treatment options for our patients."

Summary Results

As of the November 7, 2015 cutoff, the following clinical data were reported:

Twenty-one patients with relapsed or refractory NHL were enrolled into the phase 1 study; 16 of the 21 patients were response-evaluable as defined by the study protocol.
Nine of 16 (56 percent) response-evaluable NHL patients achieved an objective response.
On an intent-to-treat basis, seven of 12 (58 percent) response-evaluable NHL patients treated at or above the recommended phase 2 dose of 800 mg twice daily (BID) achieved an objective response.

Four patients remained on study at data cutoff with ongoing objective responses, including three patients who had been on drug for at least 18 months.

800 mg BID showed superior tolerability, equivalent anti-tumor activity and equivalent pharmacodynamic activity as compared to the 1600 mg BID dose.

The majority of adverse events were grade 1 or grade 2 within the 55 patients with NHL and solid tumors who were evaluable for safety. The most common adverse events, regardless of attribution, were asthenia, anorexia, thrombocytopenia, nausea, constipation, diarrhea, and vomiting. Four grade 3 or greater treatment-related adverse events have been observed including one each of: grade 3 hypertension, grade 3 liver function test elevation, grade 4 thrombocytopenia, and grade 4 neutropenia.

Study Design

This open-label, multi-center, phase 1 study is investigating tazemetostat as monotherapy in patients with relapsed or refractory B-cell Non-Hodgkin Lymphoma or advanced solid tumors. The study objectives include identification of the recommended phase 2 dose or maximum tolerated dose, safety, tolerability, pharmacokinetics and preliminary evaluation of anti-tumor activity. Five cohorts were studied in the dose escalation phase: 100 mg, 200 mg, 400 mg, 800 mg and 1600 mg; and two cohorts, 800 mg and 1600 mg, were evaluated in the dose expansion phase. All doses were given twice daily. In addition, the study included two clinical pharmacology sub-studies: one for food effect and the other for drug-drug interaction. In the food effect sub-study, patients received a single 200 mg dose of tazemetostat either fasted or immediately after a high-fat breakfast in a randomized crossover fashion with seven days between doses. Patients received 400 mg BID after completing the seven-day crossover component of the study. Five of the 21 NHL patients were in the food effect sub-study.

Expanded Tazemetostat Registration-Supporting Phase 2 Program in NHL

Epizyme is conducting an international, multi-center, phase 2 study comprised of five independent arms. This study, which began enrolling patients in the second half of 2015, will assess the safety and efficacy of 800 mg BID of tazemetostat in patients with relapsed or refractory NHL, stratified by cell of origin and EZH2 mutation status. Epizyme plans to present interim results from the phase 2 study at a medical conference in mid-2016.

About EZH2 in Cancer

EZH2 is a histone methyltransferase (HMT) that is increasingly understood to play a potentially oncogenic role in a number of cancers. These include Non-Hodgkin Lymphoma, INI1-deficient cancers such as malignant rhabdoid tumors, epithelioid sarcomas and synovial sarcoma; and a range of other solid tumors.

About Tazemetostat

Epizyme is developing tazemetostat for the treatment of non-Hodgkin lymphoma patients and patients with INI1-deficient solid tumors. Tazemetostat is a first-in-class small molecule inhibitor of EZH2 created by Epizyme using its proprietary product platform. In many human cancers, aberrant EZH2 enzyme activity results in misregulation of genes that control cell proliferation resulting in the rapid and unconstrained growth of tumor cells. Tazemetostat is the WHO International Non-Proprietary Name (INN) for EPZ-6438.

Additional information about this program, including clinical trial information, may be found here: View Source