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FDA Approves BLINCYTO® (blinatumomab) For Use In Pediatric Patients With Philadelphia Chromosome-Negative Relapsed Or Refractory B-cell Precursor Acute Lymphoblastic Leukemia

On September 1, 2016 Amgen (NASDAQ:AMGN) reported that the U.S. Food and Drug Administration (FDA) has approved the supplemental Biologics License Application (sBLA) for BLINCYTO (blinatumomab) to include new data supporting the treatment of pediatric patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) (Press release, Amgen, SEP 1, 2016, View Source [SID:1234514874]). This indication is approved under accelerated approval, and continued approval may be contingent upon verification of clinical benefit in subsequent trials.

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The approval is based on results from the Phase 1/2 ‘205, an open-label, multicenter, single-arm trial, which evaluated the efficacy and safety of BLINCYTO in pediatric patients with relapsed or refractory B-cell precursor ALL.

About Study ‘205
Study ‘205 evaluated the safety and efficacy of BLINCYTO in a Phase 1/2 open-label, multicenter, single-arm study in 93 pediatric patients with relapsed or refractory B-cell precursor ALL (second or later bone marrow relapse, any marrow relapse after allogeneic hematopoietic stem cell transplantation [alloHSCT], or refractory to other treatments and had >25 percent blasts in bone marrow). Treatment in this study has been completed and subjects are being monitored for long-term efficacy.

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, priority review and orphan drug designations by FDA, and is now approved in the U.S. for the treatment of Ph- relapsed or refractory B-cell precursor ALL.

In November 2015, BLINCYTO was granted conditional marketing authorization in the European Union for the treatment of adults with Ph- relapsed or refractory B-cell precursor ALL.

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): CRS, which may be life-threatening or fatal, 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 64% of patients receiving BLINCYTO in clinical trials experienced neurological toxicities. The median time to onset of any neurological toxicity was 4 days. The most common (≥10%) manifestations of neurological toxicity were headache, tremor, dizziness, and altered state of consciousness. Severe, life-threatening, or fatal neurological toxicities occurred in approximately 17% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. 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): TLS, which may be life-threatening or fatal, 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 median time to onset of elevated liver enzymes was 3 days. In patients receiving BLINCYTO, the majority of these events were observed in the setting of CRS. The median time to onset for these events 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.

Pancreatitis: Fatal pancreatitis has been reported in patients receiving BLINCYTO in combination with dexamethasone in clinical trials and the post-marketing setting. Evaluate patients who develop signs and symptoms of pancreatitis and interrupt or discontinue BLINCYTO and dexamethasone as needed.

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).
Immunization: Vaccination with live virus vaccines is not recommended for at least 2 weeks prior to the start of BLINCYTO treatment, during treatment, and until immune recovery following last cycle of BLINCYTO.
Adverse Reactions

The most common adverse reactions (≥ 20%) in the safety population studied in clinical trials were pyrexia, headache, nausea, edema, hypokalemia, anemia, febrile neutropenia, neutropenia, thrombocytopenia, and abdominal pain. The safety population included 225 patients weighing 45kg or more and 57 patients weighing less than 45kg.
In patients weighing greater than or equal to 45kg, serious adverse reactions were reported in 61% of patients. The most common serious adverse reactions (≥ 2%) included febrile neutropenia, pyrexia, sepsis, pneumonia, device-related infection, neutropenia, tremor, overdose, encephalopathy, infection, confusion and headache.
In patients weighing less than 45kg, serious adverse reactions were reported in 51% of patients. The most common serious adverse reactions (≥ 2%) included pyrexia, febrile neutropenia, cytokine release syndrome, convulsion, device-related infection, hypoxia, sepsis, and overdose
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 pi.amgen.com.

ChemoCentryx Reports Initial Results from Ongoing Phase Ib Clinical Trial of CCX872 in Patients with Advanced Pancreatic Cancer

On September 1, 2016 ChemoCentryx, Inc., (Nasdaq:CCXI) reported initial 12 week overall response rate (ORR) results from an ongoing open label, single arm Phase Ib clinical trial with CCX872 in patients with advanced pancreatic cancer (Press release, ChemoCentryx, SEP 1, 2016, View Source [SID:1234514870]). CCX872 is a selective inhibitor of the chemokine receptor known as CCR2.

The ongoing Phase Ib clinical study aims to evaluate the safety and effects of orally administered CCX872 when added to standard of care FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan and oxaliplatin) in patients with advanced non-resectable pancreatic cancer. Under the study protocol, patients may continue to receive CCX872 for an indefinite treatment period as long as there is no evidence of disease progression. The Company expects to report progression-free survival (PFS) by the end of 2016.

Patients enrolled in the study had advanced non-resectable pancreatic cancer (78% of patients having metastatic disease), and an Eastern Cooperative Oncology Group (ECOG) Performance Status score of less than or equal to 2. In order to assess the initial treatment effect of CCX872, the study provided for assessment of overall response rate (ORR) based on computerized tomography (CT) imaging following 12 weeks of treatment.

The pre-specified evaluable ORR population consists of all patients who have at least one post-baseline disease CT assessment. Response rate results at 12 weeks of treatment were as follows:

Pre-Specified Evaluable
Patient Population1
(N=41) ITT
Patient Population
(N=50)
Tumor control rate2 32/41 (78%) 32/50 (64%)
Overall response rate3 15/41 (37%) 15/50 (30%)
Stable disease 17/41 (41%) 17/50 (34%)
Progressive disease 9/41 (22%) 9/50 (18%)
Not evaluable4 9/50 (18%)
1 Pre-specified as the primary efficacy population = pre-defined as all patients who have a least one post baseline CT scan. ITT = all patients randomized, including those with no post baseline CT scan.
2 Tumor control rate includes stable disease, partial response and complete response.
3 Overall response rate measured by Response Evaluation Criteria for Solid Tumors version 1.1 (RECIST 1.1). All responses included in ORR were partial responses (PRs).
4 Not evaluable due to no post baseline CT scan due to early withdrawal.

CCX872 was well tolerated by advanced pancreatic cancer patients. The incidence and rate of adverse events were consistent with data reported historically for FOLFIRINOX alone, suggesting no apparent additional safety burdens of combining CCX872 with FOLFIRINOX.

"Advanced pancreatic cancer is particularly challenging to treat, and represents a very high unmet medical need," said Pirow Bekker, M.D., Ph.D., Chief Medical Officer of ChemoCentryx. "While some earlier work with this mechanism looked at non-metastatic pancreatic cancer patients, we were keen on examining the effects of CCR2 inhibition in non-operable, metastatic disease in a multi-center setting. Given patients in our study may continue to receive treatment with CCX872 for as long as they are in a progression-free state, we will continue the study according to plan and evaluate progression-free survival later this year. Those data, as well as the potential longer term survival beyond that time, will help us in determining how best to proceed with CCR2 inhibition for pancreatic cancer."

About CCX872 Phase Ib Trial Design
The open-label, multi-center, ongoing Phase Ib clinical trial is designed to evaluate the safety and efficacy of orally administered CCX872 plus FOLFIRINOX in 50 patients with non-resectable pancreatic cancer. Patients receive 150 mg CCX872 twice daily for 12 weeks. After 12 weeks, patients who achieved stable disease or better (as measured by Response Evaluation Criteria In Solid Tumors, or RECIST 1.1), are eligible to continue on study for at least an additional 12 weeks unless disease progression occurs. Per protocol, the Eastern Cooperative Oncology Group (ECOG) performance status of patients in the trial is 0, 1 or 2. The primary efficacy measurement of the trial is progression-free survival (PFS) following at least 24 weeks of treatment.

About Pancreatic Cancer
It is estimated that over 337,000 cases of pancreatic cancer are diagnosed worldwide every year. In the United States, the annual incidence of pancreatic cancer is approximately 45,000; prevalence is only negligibly higher owing to the poor survival rates on current therapy. Within five years of diagnosis, 93 percent of patients die from their disease. Current standards of care include chemotherapeutic regimens that have significant toxicities and, in a minority of cases, surgical resection.

Amgen Obtains Global Development And Commercial Rights From Boehringer Ingelheim For Investigational BiTE® Immuno-Oncology Drug For Multiple Myeloma

On September 1, 2016 Amgen (NASDAQ:AMGN) and Boehringer Ingelheim reported that Amgen has acquired global development and commercial rights from Boehringer Ingelheim for BI 836909 (AMG 420), a bispecific T cell engager (BiTE) that targets B-cell maturation antigen (BCMA), a potential target for multiple myeloma (Press release, Amgen, SEP 1, 2016, View Source [SID:1234514867]). BI 836909 (AMG 420) is currently in Phase 1 studies. BI 836909 (AMG 420) was originally licensed to Boehringer Ingelheim by Micromet before the company was acquired by Amgen in 2012.

Under the provisions of the agreement, Amgen will work with Boehringer Ingelheim to assume responsibility for the clinical development of BI 836909 (AMG 420), transfer manufacturing, and lead global regulatory activity moving forward. Amgen will also receive worldwide commercialization rights for BI 836909 (AMG 420). Prior to this agreement, Boehringer Ingelheim held global development and commercialization rights. Financial terms of the agreement are not being disclosed.

"Obtaining global rights to BI 836909 (AMG 420) advances Amgen’s immuno-oncology strategy, allowing us to leverage our expertise with the BiTE platform to target BCMA in the multiple myeloma setting," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Multiple myeloma is a rare and aggressive blood cancer and despite new advances there is currently no cure.1-3 BI 836909 (AMG 420) allows us to explore a potential new treatment approach that harnesses the immune system to fight multiple myeloma."

"Boehringer Ingelheim is delighted that Amgen will continue our successful development of this important compound for multiple myeloma," said Dr. Jörg Barth, corporate senior vice president, Therapy Area Head Oncology at Boehringer Ingelheim. "Given Amgen’s focus in this disease area, we are convinced this best supports the future development for BI 836909 (AMG 420) and the goal to ultimately offer new treatment options for patients. Immuno-oncology and T cell engagers remain a key area of focus for Boehringer Ingelheim as well as providing innovative treatments for lung and blood cancers."

About BI 836909 (AMG 420)
BI 836909 (AMG 420) is a bispecific T cell engager (BiTE) that is under investigation for the treatment of multiple myeloma. BI 836909 (AMG 420) targets B-cell maturation antigen (BCMA), a target in multiple myeloma due to its restricted normal tissue expression and uniform expression on multiple myeloma cells. BI 836909 (AMG 420) is currently being evaluated in Phase 1 studies.

About BiTE Technology
Bispecific T cell engager (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. For more information, visit www.biteantibodies.com.

Sunesis Pharmaceuticals Announces Poster Presentation on Preliminary Results from the Phase 1A Healthy Volunteer Study Evaluating Oral Non-Covalent BTK-inhibitor SNS-062 at the European School of Haematology’s 2nd International Conference on New Concepts in B-Cell Malignancies

On September 1, 2016 Sunesis Pharmaceuticals, Inc. (Nasdaq:SNSS) reported that a poster detailing preliminary results from the Company’s Phase 1A study in healthy volunteers evaluating oral non-covalent BTK-inhibitor SNS-062 will be presented at the European School of Haematology’s 2nd International Conference on New Concepts in B-Cell Malignancies being held September 9-11, 2016, at the Estoril Congress Centre in Estoril, Portugal (Press release, Sunesis, SEP 1, 2016, View Source [SID:1234514866]).

The details for the poster presentation are as follows:

Date & Time: Saturday, September 10, 2016, from 6:50 p.m. to 8:20 p.m. Central European Time

Poster Title: A Phase 1a Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of the Noncovalent Bruton Tyrosine Kinase (BTK) Inhibitor SNS-062 in Healthy Subjects: Preliminary Results

The poster will be available on the Sunesis website following the presentation.

OncoMed Pharmaceuticals Completes Enrollment of Phase 2 YOSEMITE Clinical Trial of Demcizumab in Pancreatic Cancer

On September 1, 2016 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), a clinical development-stage biopharmaceutical company focused on discovering and developing novel anti-cancer stem cell and immuno-oncology therapeutics, reported the completion of patient enrollment of 207 patients in the randomized Phase 2 "YOSEMITE" clinical trial of demcizumab (anti-DLL4, OMP-21M18) for the treatment of first-line metastatic pancreatic cancer (Press release, OncoMed, SEP 1, 2016, View Source [SID:1234514865]). Topline results are expected in the first half of 2017.

The YOSEMITE trial was designed to assess the efficacy and safety of demcizumab in combination with Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine (standard of care) compared to standard of care alone. The Phase 2 dose of demcizumab was 3.5 mg/kg every two weeks for up to 70 days. The primary endpoint of YOSEMITE is progression-free survival. Secondary and exploratory endpoints include overall survival, response rate, pharmacokinetics, immunogenicity, safety and biomarker analyses. Patients enrolled in the YOSEMITE Phase 2 were randomized into one of three study arms receiving 1) standard of care plus one course of demcizumab, 2) standard of care plus demcizumab followed by a second course of demcizumab after a 98-day wash-out period or 3) standard of care plus placebo. The YOSEMITE Phase 2 trial was conducted at 49 clinical sites in the U.S., Europe and Australia. OncoMed initiated YOSEMITE in April 2015.

"We would like to thank the patients and their caregivers as well as the investigators and study teams for their participation and support in this trial," said Jakob Dupont, M.D., Chief Medical Officer of OncoMed. "Improving outcomes for patients with metastatic pancreatic cancer has proven to be highly challenging and the need for additional treatment options is of great importance. In Phase 1b studies, demcizumab combined with standard of care demonstrated promising response rates and survival trends, and we look forward to gaining further insights into demcizumab’s potential in pancreatic cancer from the Phase 2 YOSEMITE trial."

In OncoMed’s Phase 1b clinical trial of demcizumab truncated dosing and Abraxane plus gemcitabine, 14 of 28 (50%) patients evaluable for response achieved partial responses (unconfirmed) and another 11 (39%) achieved stable disease. Among 32 patients evaluable for survival in the Phase 1b, median progression-free survival was 7.1 months and median overall survival was 12.7 months for the patients who received one truncated 70-day course of demcizumab with Abraxane plus gemcitabine. The combination of demcizumab and Abraxane plus gemcitabine was generally well tolerated with fatigue, nausea and vomiting being the most common drug related toxicities. Final results from OncoMed’s Phase 1b trial of demcizumab were presented at the 2016 Gastrointestinal Cancers Symposium.

About Pancreatic Cancer
Pancreatic cancer is the third leading cause of cancer-related deaths. According to the American Cancer Society, each year in the United States there are approximately 49,000 new cases of pancreatic cancer and 41,000 deaths. The majority of patients with pancreatic cancer are diagnosed after their cancer has spread locally and/or metastasized to distant organs. The average life expectancy after the diagnosis of metastatic pancreatic cancer is less than one year.

About Demcizumab (anti-DLL4, OMP-21M18)
Demcizumab is a humanized monoclonal antibody targeting Delta-like Ligand 4 (DLL4), a key member of the Notch signaling pathway. Based on preclinical studies, demcizumab appears to have a multi-pronged mechanism of action: halting cancer stem cell growth and reducing cancer stem cell frequency, disrupting angiogenesis in the tumor and augmenting anti-tumor immune responses by decreasing tumor myeloid-derived suppressor cells (MDSCs).

Demcizumab is currently being studied in two randomized Phase 2 clinical trials. The YOSEMITE trial is testing demcizumab with Abraxane plus gemcitabine versus Abraxane plus gemcitabine alone in first-line advanced pancreatic cancer patients. The DENALI trial is testing demcizumab with pemetrexed and carboplatin versus pemetrexed and carboplatin alone in first-line advanced non-small cell lung cancer patients. A Phase 1b trial combining demcizumab with the anti-PD1 antibody pembrolizumab in solid tumor patients was also initiated in early 2016. Demcizumab is part of OncoMed’s collaboration with Celgene Corporation.

Patients interested in learning more about participating in one of OncoMed’s ongoing clinical trials may learn more by calling 1-866-914-7347 or emailing [email protected]