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Chugai Obtains Approval of Humanized Anti-PD-L1 Monoclonal Antibody, “TECENTRIQ® Intravenous Infusion 1200mg” for the Treatment of Unresectable, Advanced or Recurrent Non-small Cell Lung Cancer

On January 18, 2018 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it has obtained approval of its humanized anti-PD-L1 (Programmed Death Ligand-1) monoclonal antibody, "TECENTRIQ Intravenous Infusion 1200mg" (generic name: atezolizumab [recombinant]) from the Ministry of Health, Labour and Welfare (MHLW) for the treatment of "unresectable advanced or recurrent non-small cell lung cancer (NSCLC) (Press release, Chugai, JAN 18, 2018, View Source [SID1234523305])."

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"This is the first approval for TECENTRIQ in Japan, and it also represents the first step for Chugai to provide cancer immunotherapy," said Chugai’s President & COO, Tatsuro Kosaka. "We have been preparing for the new launch to provide TECENTRIQ for all patients as early as possible, and will take every measures to deliver the information needed to promote its appropriate use."

TECENTRIQ is a PD-L1 targeting monoclonal antibody created by Genetench, a member of the Roche Group. PD-L1 is a protein expressed on tumor and tumor-infiltrating immune cells that blocks T cell activity by binding with PD-1 and B7.1 receptors on T cell surface. By inhibiting PD-L1, TECENTRIQ may enable the activation of T cells and boost immune response against cancer cells.

TECENTRIQ is already approved in the European Union, United States and more than 50 countries for people with previously treated metastatic NSCLC and for people with locally advanced or metastatic urothelial cancer who are not eligible for cisplatin chemotherapy, or who have had disease progression during or following platinum-containing therapy. In Japan, Chugai has been conducting seven clinical studies in the NSCLC setting to evaluate TECENTRIQ alone or in combination with other drugs. In addition to NSCLC studies, several phase III studies are ongoing for small-cell lung cancer, urotherial carcinoma, breast cancer, renal cell carcinoma, ovarian cancer and prostate cancer.

In Japan, the annual prevalence of lung cancer is estimated to be approximately 134,000 in 2015 (male: 91,000, female: 43,000). The annual mortality of lung cancer, the leading cause of cancer deaths in Japan, is approximately 77,000 (male: 55,000, female: 22,000; predicted figure for 2015).*

As a top pharmaceutical company in the field of oncology in Japan, Chugai is committed to contribute to patients with lung cancers and medical professionals by offering TECENTRIQ as a new treatment option.

About conditions for approval of TECENTRIQ
A drug use surveillance of all patients who receive TECENTRIQ must be conducted until the data on a given number of patients is accumulated.

About the drug use surveillance of TECENTRIQ (All-case registration surveillance)
The all-case registration surveillance is scheduled to collect the data of 1,000 patients who receive TECENTRIQ treatment. Once data for the first 1,000 cases is accumulated, the data will be reviewed to determine whether a new surveillance or further safety measures should be conducted. Results of the surveillance will be reported to the regulatory authorities, and the data shall be announced at future scientific meetings.

Note: The description of INDICATIONS in the Japanese package insert
The following description is noted as in the INDICATIONS:

Efficacy and safety of TECENTRIQ in chemotherapy-naïve patients have not been established.
Efficacy and safety have not been established for postoperative adjuvant chemotherapy with TECENTRIQ.
Eligible patients should be selected after closely reading the CLINICAL STUDIES section, which provides information such as the prior treatment history of patients in the clinical studies, in order to gain a thorough understanding of the efficacy and safety of TECENTRIQ.

Kite Announces Clinical Collaboration to Evaluate Investigational Combination of YescartaTM (Axicabtagene Ciloleucel) and Pfizer’s Utomilumab in Large B-Cell Lymphoma

On January 18, 2018 Kite, a Gilead Company (Nasdaq: GILD), reported it has entered into a clinical trial collaboration with Pfizer, Inc. to evaluate the safety and efficacy of the investigational combination of Yescarta (axicabtagene ciloleucel) and Pfizer’s utomilumab, a fully humanized 4-1BB agonist monoclonal antibody, in patients with refractory large B-cell lymphoma (Press release, Kite Pharma, JAN 18, 2018, View Source;p=irol-newsArticle&ID=2327256 [SID1234523300]). A multi-center Phase 1/2 study sponsored by Kite is expected to begin in 2018. The results of this study will be used to evaluate options for further development of this combination, or similar combinations between Kite’s engineered T cell products and utomilumab.

Yescarta is the first chimeric antigen receptor T (CAR T) cell therapy to be indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. Yescarta is not indicated for patients with primary central nervous system lymphoma.

Utomilumab, also known as PF-05082566, is an investigational 4-1BB agonist that has been shown in preclinical models to enhance T cell mediated immune responses. Pfizer is currently investigating utomilumab in both hematologic cancers and solid tumors as a single agent and in combination with other anti-cancer therapies. Evidence also suggests that 4-1BB, a costimulatory protein expressed on activated T cells, is upregulated upon exposure to CD19-expressing tumor cells. Utomilumab could potentially enhance T cell proliferation and activity by augmenting the CD28 costimulatory domain of Yescarta with exogenous 4-1BB signaling.

"Kite is committed to realizing the full potential of Yescarta and other cell therapy technologies across a range of cancers," said David Chang, MD, PhD, Worldwide Head of Research and Development and Chief Medical Officer at Kite. "We are pleased to collaborate with Pfizer on this study with utomilumab, which adds to the growing number of combination approaches we are exploring with Yescarta for patients living with lymphoma."

The combination of Yescarta and utomilumab is investigational and has not been proven safe and effective.

U.S. Important Safety Information for Yescarta

BOXED WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving Yescarta. Do not administer Yescarta to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving Yescarta, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with Yescarta. Provide supportive care and/or corticosteroids as needed.
Yescarta is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta REMS.

Cytokine Release Syndrome (CRS)

CRS, including fatal or life-threatening reactions, occurred following treatment with Yescarta. In Study 1, CRS occurred in 94% (101/108) of patients receiving Yescarta, including ≥ Grade 3 (Lee grading system) CRS in 13% (14/108) of patients. Among patients who died after receiving Yescarta, four had ongoing CRS events at the time of death. The median time to onset was 2 days (range: 1 to 12 days) and the median duration of CRS was 7 days (range: 2 to 58 days). Key manifestations of CRS include fever (78%), hypotension (41%), tachycardia (28%), hypoxia (22%), and chills (20%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).

Ensure that 2 doses of tocilizumab are available prior to infusion of Yescarta. Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for 4 weeks after infusion. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated.

Neurologic Toxicities

Neurologic toxicities, that were fatal or life-threatening, occurred following treatment with Yescarta. Neurologic toxicities occurred in 87% of patients. Ninety-eight percent of all neurologic toxicities occurred within the first 8 weeks of Yescarta infusion, with a median time to onset of 4 days (range: 1 to 43 days). The median duration of neurologic toxicities was 17 days. Grade 3 or higher neurologic toxicities occurred in 31% of patients.

The most common neurologic toxicities included encephalopathy (57%), headache (44%), tremor (31%), dizziness (21%), aphasia (18%), delirium (17%), insomnia (9%) and anxiety (9%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events including leukoencephalopathy and seizures occurred with Yescarta. Fatal and serious cases of cerebral edema have occurred in patients treated with Yescarta.

Monitor patients at least daily for 7 days at the certified healthcare facility following infusion for signs and symptoms of neurologic toxicities. Monitor patients for signs or symptoms of neurologic toxicities for 4 weeks after infusion and treat promptly.

Yescarta REMS

Because of the risk of CRS and neurologic toxicities, Yescarta is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta REMS. The required components of the Yescarta REMS are:

Healthcare facilities that dispense and administer Yescarta must be enrolled and comply with the REMS requirements. Certified healthcare facilities must have on-site, immediate access to tocilizumab, and ensure that a minimum of two doses of tocilizumab are available for each patient for infusion within 2 hours after Yescarta infusion, if needed for treatment of CRS.
Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense or administer Yescarta are trained about the management of CRS and neurologic toxicities.

Further information is available at www.YescartaREMS.com or 1-844-454-KITE (5483).

Hypersensitivity Reactions

Allergic reactions may occur with the infusion of Yescarta. Serious hypersensitivity reactions including anaphylaxis, may be due to dimethyl sulfoxide (DMSO) or residual gentamicin in Yescarta.

Serious Infections

Severe or life-threatening infections occurred in patients after Yescarta infusion. In Study 1, infections (all grades) occurred in 38% of patients. Grade 3 or higher infections occurred in 23% of patients. Grade 3 or higher infections with an unspecified pathogen occurred in 16% of patients, bacterial infections in 9%, and viral infections in 4%. Yescarta should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after Yescarta infusion and treat appropriately. Administer prophylactic anti-microbials according to local guidelines.

Febrile neutropenia was observed in 36% of patients after Yescarta infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids and other supportive care as medically indicated.

Viral Reactivation

Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients treated with drugs directed against B cells. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

Prolonged Cytopenias

Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and Yescarta infusion. In Study 1, Grade 3 or higher cytopenias not resolved by Day 30 following Yescarta infusion occurred in (28%) of patients and included thrombocytopenia (18%), neutropenia (15%), and anemia (3%). Monitor blood counts after Yescarta infusion.

Hypogammaglobulinemia

B-cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with Yescarta. In Study 1, hypogammaglobulinemia occurred in 15% of patients. Monitor immunoglobulin levels after treatment with Yescarta and manage using infection precautions, antibiotic prophylaxis and immunoglobulin replacement.

The safety of immunization with live viral vaccines during or following Yescarta treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during Yescarta treatment, and until immune recovery following treatment with Yescarta.

Secondary Malignancies

Patients treated with Yescarta may develop secondary malignancies. Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing.

Effects on Ability to Drive and Use Machines

Due to the potential for neurologic events, including altered mental status or seizures, patients receiving Yescarta are at risk for altered or decreased consciousness or coordination in the 8 weeks following Yescarta infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

Adverse Reactions

The most common adverse reactions (incidence ≥ 20%) include CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections-pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias. Serious adverse reactions occurred in 52% of patients. The most common serious adverse reactions (> 2%) include encephalopathy, fever, lung infection, febrile neutropenia, cardiac arrhythmia, cardiac failure, urinary tract infection, renal insufficiency, aphasia, cardiac arrest, Clostridium difficile infection, delirium, hypotension, and hypoxia.

The most common (≥ 10%) Grade 3 or higher reactions include febrile neutropenia, fever, CRS, encephalopathy, infections-pathogen unspecified, hypotension, hypoxia and lung infections.

U.S. Indication for Yescarta

Yescarta is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.

Limitation of Use: Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma.

Phase 1b/2 Study of Margetuximab in Combination with Pembrolizumab Presented at 2018 ASCO Gastrointestinal Cancers Symposium

On January 18, 2018 MacroGenics, Inc. (NASDAQ:MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported presentation of data from its clinical trial of margetuximab plus pembrolizumab for patients with advanced gastric and gastroesophageal junction (GEJ) cancers in a poster session at the 2018 ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium in San Francisco, California (Press release, MacroGenics, JAN 18, 2018, View Source [SID1234523293]). The poster was titled "Phase 1b/2 Study of Margetuximab Plus Pembrolizumab in Advanced HER2+ Gastroesophageal Junction or Gastric Adenocarcinoma."

This Phase 1b/2 open-label, dose escalation study evaluates margetuximab, an Fc-optimized anti-HER2 monoclonal antibody, in combination with pembrolizumab, an anti-PD-1 antibody. The trial seeks to characterize the safety, tolerability, maximum tolerated dose, and preliminary anti-tumor activity of this combination. Enrolled patients had relapsed or refractory advanced HER2+ gastric or GEJ cancer with disease progression after or resistance to treatment with trastuzumab plus chemotherapy. Study patients were enrolled irrespective of PD-L1 expression status.

A Phase 1b dose escalation segment of the study tested dose levels of 10 and 15 mg/kg margetuximab in combination with a flat dose of 200 mg pembrolizumab every three weeks. After completion of dose escalation, Phase 2 dose expansion cohorts were enrolled, including a 30 patient cohort in North America and a 30 patient cohort in Asia. Sixty dose expansion patients received margetuximab at 15 mg/kg and 200 mg of pembrolizumab every three weeks.

Acceptable tolerability was observed in the safety population of 67 patients. Grade 3 or higher treatment-related adverse events (TRAE) occurred in 11.9% of patients. The most common TRAE of any grade was fatigue (14.9%).

As of the December 4, 2017 data cut-off date, responses were evaluable from 51 patients, including 25 with gastric and 26 with GEJ cancer. The Overall Response Rate (ORR) was higher in patients with gastric vs. GEJ cancer (32% vs. 4%). ORR across all patients in the study was 18% (six confirmed and three unconfirmed patients). Similarly, Disease Control Rate (including partial responses and stable disease) was higher in patients with gastric vs. GEJ cancer (72% vs. 38%). Median progression-free survival was also higher in patients with gastric vs. GEJ cancer (5.5 vs. 1.4 months).

"We are encouraged by the tolerability and anti-tumor activity of this novel, chemotherapy-free regimen combining margetuximab with an anti-PD-1 mAb for treatment of patients with advanced HER2+ gastric cancer," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "We are expanding the study by enrolling 25 additional gastric cancer patients and will continue to evaluate biomarkers, including HER2 and PD-L1 expression, to determine the patients who are most likely to benefit from margetuximab plus anti-PD-1 therapy. We expect to provide an update on these data later this year and define future development options for this regimen in the context of existing standard-of-care."

The poster presented at the 2018 ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium is available for download from the Events & Presentations page on MacroGenics’ website at View Source

About Margetuximab

Margetuximab is an Fc-optimized monoclonal antibody that targets the human epidermal growth factor receptor 2, or HER2 oncoprotein. HER2 is expressed by tumor cells in breast, gastric, gastroesophageal, bladder and other forms of solid tumor cancers, making it a key marker for biologic therapy. The Phase 1b/2 study of margetuximab in gastric and gastroesophageal cancer incorporates pembrolizumab, which is provided by Merck & Co., under a previously announced arrangement. MacroGenics is also studying margetuximab as a potential treatment for metastatic breast cancer in a Phase 3 study called SOPHIA, for which an interim futility analysis is expected to be completed by the end of January 2018.

Daiichi Sankyo Presents Updated Data for DS-8201 in Patients with HER2-Expressing Gastric Cancer at ASCO 2018 Gastrointestinal Cancers Symposium

On January 18, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that updated phase 1 safety and efficacy data for DS-8201, an investigational HER2-targeting antibody drug conjugate (ADC), in a subgroup of patients with HER2-expressing gastric cancer previously treated with trastuzumab and chemotherapy were presented during a poster session at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium in San Francisco, California (Press release, Daiichi Sankyo, JAN 18, 2018, View Source [SID1234523291]).

Updated preliminary subgroup analysis results in 44 of 45 efficacy evaluable patients with HER2-expressing gastric cancer or gastroesophageal junction adenocarcinoma previously treated with trastuzumab and chemotherapy showed that DS-8201 demonstrated a confirmed overall response rate of 45.5 percent (20 of 44 patients) and a disease control rate of 81.8 percent (36 of 44 patients). Median duration of response was 7.0 months (95 percent CI: NR). The Kaplan-Meier estimate of median progression-free survival was 5.8 months (95 percent CI: 3.0, 8.3). A total of 17 out of 44 patients were continuing to receive treatment at the time of data cut-off.

"Gastric cancer can be difficult to treat due to its molecular complexity, and currently there are no HER2- targeted therapies or antibody drug conjugates approved for HER2-positive advanced gastric cancer that progresses following treatment with trastuzumab," said Toshihiko Doi, MD, PhD, Department of Experimental Therapeutics, National Cancer Center Hospital East. "These phase 1 results are encouraging and demonstrate the importance of continuing to study the potential of DS-8201 in treating HER2-positive gastric cancer. The pivotal phase 2 study is currently underway."

A subgroup analysis of 23 patients previously treated with CPT-11 (irinotecan) showed that DS-8201 demonstrated a confirmed overall response rate of 43.5 percent (10 of 23 patients) and a disease control rate of 82.6 percent (19 of 23 patients). Median duration of response was 6.9 months (95 percent CI: NR).

The Kaplan-Meier estimate of median progression-free survival for this subgroup of patients was 4.1 months (95 percent CI: 2.5, 8.3).

"These data from patients with HER2-positive gastric cancer who have failed HER2-targeted therapy combined with chemotherapy, and for many who also failed irinotecan as a systemic chemotherapy suggest that the ADC technology of DS-8201 appears able to deliver on what it was specifically researched and innovated for: a smart chemotherapy approach to tumors expressing some degree of HER2 receptors, regardless of prior treatment with a topoisomerase I inhibitor," said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. "A comprehensive translational research effort is planned and underway to further understand the biological basis for the observed activity, including the role of tumor heterogeneity and HER2 expression, the mechanisms of resistance that may have contributed to failing prior lines of treatment, and factors more directly related to the unique pharmacological profile of DS-8201."

Updated preliminary safety data for this subgroup of trastuzumab-treated HER2-expressing gastric cancer patients were also reported. The most common adverse events (>30 percent, any grade) included nausea (71.1 percent), decreased appetite (64.4 percent), platelet count decreased (33.3 percent), white blood cell count decreased (33.3 percent) and constipation (31.1 percent). Grade 3 adverse events occurring in >10 percent of patients included anemia (24.4 percent), neutrophil count decreased (15.6 percent), platelet count decreased (13.3 percent) and white blood cell count decreased (11.1 percent). Grade 4 adverse events included platelet count decreased (4.4 percent), white blood cell count decreased (4.4 percent) and neutrophil count decreased (4.4 percent). Three patients discontinued treatment due to treatment-emergent adverse events (pneumonia, decreased appetite, and pneumonitis). Two potential cases of interstitial lung disease (ILD) were reported by the investigators (one grade 1 and one grade 3) in gastric cancer subjects and together with all reported or suspected ILD cases are being assessed by an independent ILD adjudication committee. These include two cases of potential Grade 5 pneumonitis previously reported in the breast cancer cohorts.

Based on these phase 1 data, patients are currently being enrolled in the pivotal, phase 2 open-label DESTINY-Gastric01 study investigating the safety and efficacy of DS-8201 in patients with HER2-positive advanced gastric cancer or gastroesophageal junction adenocarcinoma (defined as IHC3+ or IHC2+/ISH+) who have progressed on two prior regimens including fluoropyrimidine agent, platinum agent and trastuzumab. For more information about this study, visit www.ClinicalTrials.gov.

Unmet Need in Gastric Cancer

Gastric cancer is the fifth most common cancer worldwide, with nearly one million new cases reported in 2012.1 Approximately one in five gastric cancers overexpress HER2, a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells.2 HER2-expressing gastric cancer is an area of unmet medical need as advances in the treatment of the disease have been limited, largely due to its genetic complexity and heterogeneity.3 Currently, there are no approved HER2-targeting therapy options for patients with HER2-positive advanced gastric cancer after treatment with trastuzumab.

About the DS-8201 Phase 1 Study

The open-label, two-part phase 1 study is currently evaluating DS-8201 in patients with advanced/

unresectable or metastatic solid tumors that are refractory or intolerant to standard treatment, or for whom no standard treatment is available. The primary objective of the dose escalation phase of the study was to assess the safety and tolerability of DS-8201 and determine the maximum tolerated dose. Data from this part of the study were published in the Lancet Oncology.4

In the dose expansion part of the phase 1 study, DS-8201 is given to patients with HER2-positive advanced or metastatic breast cancer or gastric cancer, HER2 low-expressing breast cancer or other HER2-expressing or mutant solid tumors. Patient enrollment in the two breast cancer cohorts and the HER2-expressing solid tumors cohort is ongoing in the U.S. and Japan. For more information about the study, please visit ClinicalTrials.gov.

About DS-8201

DS-8201 is the lead product in the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary ADC technology, DS-8201 is a smart chemotherapy comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

DS-8201 is currently in pivotal phase 2 clinical development for HER2-positive unresectable and/or metastatic breast cancer resistant or refractory to ado-trastuzumab emtansine (T-DM1) (DESTINY-Breast01), pivotal phase 2 development for HER2-positive advanced gastric cancer resistant or refractory to trastuzumab (DESTINY-Gastric01), and phase 1 development for other HER2-expressing advanced/unresectable or metastatic solid tumors.

DS-8201 has been granted Breakthrough Therapy designation for the treatment of patients with HER2-positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after ado-trastuzumab emtansine (T-DM1), and Fast Track designation for the treatment of HER2-positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2-targeted therapies including T-DM1 by the U.S. Food and Drug Administration (FDA). DS-8201 is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

About Daiichi Sankyo Cancer Enterprise

The vision of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by three pillars including our investigational Antibody Drug Conjugate Franchise, Acute Myeloid Leukemia Franchise and Breakthrough Science Franchise, we aim to deliver seven distinct new molecular entities over eight years during 2018 to 2025. Our powerful research engines include two laboratories for biologic/

immuno-oncology and small molecules in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. Compounds in pivotal stage development include: DS-8201, an antibody drug conjugate (ADC) for HER2-expressing breast, gastric and other cancers; quizartinib, an oral selective FLT3 inhibitor, for newly-diagnosed and relapsed/refractory acute myeloid leukemia (AML) with FLT3-ITD mutations; and pexidartinib, an oral CSF-1R inhibitor, for tenosynovial giant cell tumor (TGCT). For more information, please visit: www.DSCancerEnterprise.com

CBMG Accelerates Cell Therapy Manufacturing with GE Healthcare’s New Start-to-Finish Solution

On January 18, 2018 Cellular Biomedicine Group Inc. (NASDAQ: CBMG) (CBMG or the Company), a leading clinical-stage biopharmaceutical firm engaged in the development of immunotherapies for cancer, reported its plan to configure part of its facility in Shanghai with GE Healthcare’s FlexFactory platform, which is expected to be designed to speed up manufacturing timelines for its cell therapy clinical trials and commercial launch (Press release, Cellular Biomedicine Group, JAN 18, 2018, View Source [SID1234523290]).

There are more than 900 regenerative medicine trials underway globally, including trials in cell and gene therapy, a 19 percent increase since 2016.[1] Despite the increased number of precision medicine trials, gaps exist in how to manufacture these precise therapies to meet demand. Scalable integrated solutions to support the transition from clinical trials to commercialization have been limited. Many of the multiple cell therapy manufacturing process steps[2] remain largely unintegrated and manual, with open transfers between steps increasing contamination risk. To address these challenges and allow for reproducible manufacturing of cell therapies, GE Healthcare has developed FlexFactory for cell therapy, a scalable, semi-automated end-to-end platform.

"This is a productivity revolution in the CAR-T space – this new generation of semi-automated and standardized CAR-T manufacturing capabilities created by GE Healthcare and CBMG may allow cell therapy to provide an optimal platform and opportunity for general oncology patients. This long-term collaboration with GE could help us utilize digital technology, semi-automation and analytics, in an effort to reduce overall costs, and deliver treatments to patients more efficiently," said Tony (Bizuo) Liu, Chief Executive Officer, CBMG. GE Healthcare’s FlexFactory solution would support CBMG by providing process development and training services, cell processing equipment, semi-automation capabilities, and digital connectivity solutions – all of which support current good manufacturing practices (cGMP)-compliant manufacturing. CBMG plans to use its FlexFactory to speed up its timelines for commercializing its CAR T-cell therapies, targeting various blood and solid tumor cancers.

"With the rate in which cell therapies are moving through clinical trials, we understand how critentre for Commercialization of Regenerative Medicine (CCRM), a leader in developing and commercializing regenerative medicine technologies and cell and gene therapies, GE Healthcare expects to provide CBMG with process development services. The combined GE and CCRM process development team is comprised of 35 scientists and engineers with expertise in advanced therapeutic cell technologies, helping bridge the gap between research protocols and industrial manufacturing. GE and CCRM expects to support CBMG in increasing process efficiency by establishing a robust process development effort focused on simplifying, integrating and automating the manufacturing workflow.

"CCRM and GE Healthcare established the Centre for Advanced Therapeutic Cell Technologies, or CATCT, to industrialize cell manufacturing and accelerate the efforts of companies working with cell and gene therapies. The partnership between CBMG and GE is an exciting opportunity for the team at CCRM to demonstrate its process development skills and knowledge in overcoming cell therapy production challenges. We look forward to enabling CBMG in its efforts to commercialize its CAR T-cell therapy to treat patients with various blood and solid tumor cancers," said Michael May, President and CEO, CCRM.