On June 4, 2016 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that it will present updated survival data from the phase II study POPLAR, in people with previously treated advanced non-small cell lung cancer (NSCLC) (Press release, Hoffmann-La Roche , JUN 4, 2016, View Source [SID:1234513042]). The study results demonstrate a clear effect of Tecentriq on the likelihood of survival (Hazard Ratios, HR) with continued improvement as data mature. The earliest data analysis showed an overall survival (OS) benefit of 11.4 months (HR=0.77. CI: 95%) for Tecentriq compared to 12.6 months (HR=0.69. CI 95%) for this updated analysis. In addition, median duration of response (mDOR) has also improved with additional follow-up, from 14.3 months (HR=0.41. CI: 95%) in the initial analysis to 18.6 months (HR 0.32, CI: 95%) in the current data analysis. There were no new or unexpected safety signals, a finding consistent with earlier study results.

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"These results are very encouraging because they highlight that the benefits associated with Tecentriq have increased with time, and are not restricted to people with high levels of PD-L1 expression in this type of lung cancer," said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development at Roche. "These data show that longer follow-up is necessary to fully realise the advantages of cancer immunotherapies and traditional means to describe clinical benefit, like progression free survival, may not be the most sensitive measure for this class of treatment."

The U.S. Food and Drug Administration (FDA) accepted the company’s Biologics License Application (BLA) and granted Priority Review for Tecentriq for the treatment of people with locally advanced or metastatic NSCLC whose disease expresses the protein PD-L1, as determined by an FDA-approved test, and who have progressed on or after platinum-containing chemotherapy. The FDA will make a decision on approval by 19 October, 2016.

Updated results of the POPLAR study will be presented by David Smith, Compass Oncology, Vancouver, Canada (Abstract #9028) on Saturday, 4 June, 8:00–11:30 am CDT.

Further information on Roche’s contribution to the ASCO (Free ASCO Whitepaper) 2016 scientific programme, the company’s wider progress in cancer care and key data being presented at the conference will be featured at a Roche investor briefing on Sunday 5 June between 6pm – 8pm CDT. This event is independently organised by Roche and is open to analysts attending the ASCO (Free ASCO Whitepaper) 2016 Annual Meeting. To register for the Roche investor briefing, please use the following link:
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To learn more about Roche’s personalised cancer immunotherapy programme and Roche’s contribution to ASCO (Free ASCO Whitepaper) 2016, please follow Roche on Twitter via @Roche. You can keep up to date with ASCO (Free ASCO Whitepaper) 2016 Annual Meeting news and updates by using the hashtag #ASCO16.

About the POPLAR study
POPLAR is a multicentre, open-label, randomised phase II study evaluating the efficacy and safety of Tecentriq compared with chemotherapy (docetaxel) in people with previously treated recurrent locally advanced or metastatic NSCLC. Patients were randomised to receive either Tecentriq 1200 mg intravenously every three weeks or docetaxel 75 mg/m2 intravenously every three weeks. The study enrolled 287 people with previously treated, advanced NSCLC.

The primary endpoint was OS; secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. People were stratified by PD-L1 expression on tumour-infiltrating immune cells (ICs), histology and prior lines of therapy. PD-L1 expression was assessed for both tumour cells (TCs) and ICs; people were scored as TC0, 1, 2 or 3 and IC0, 1, 2 or 3 with a companion diagnostic immunohistochemistry (IHC) test being developed by Roche Diagnostics.
Overall Survival (OS) Benefit with Tecentriq from January 2015 – December 2015:
January – OS benefit of 11.4 months (HR=0.77. CI: 0.55-1.06)
May – OS benefit of 12.6 months (HR=0.73. CI: 0.53-0.99),
December – OS benefit of 12.6 months (HR=0.69. CI: 0.52-0.92)
POPLAR updated OS data

About non-small cell lung cancer
Lung cancer is the leading cause of cancer death globally. Each year 1.59 million people die as a result of the disease; this translates into more than 4,350 deaths worldwide every day. Lung cancer can be broadly divided into two major types: NSCLC and small cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases.

About Tecentriq (atezolizumab)
Tecentriq is a monoclonal antibody designed to target and bind to a protein called PD-L1 (programmed death ligand-1), which is expressed on tumour cells and tumour-infiltrating immune cells. PD-L1 interacts with PD-1 and B7.1, both found on the surface of T cells, causing inhibition of T cells. By blocking this interaction, Tecentriq may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells.

About Roche in cancer immunotherapy
For more than 50 years, Roche has been developing medicines with the goal to redefine treatment in oncology. Today, we’re investing more than ever in our effort to bring innovative treatment options that help a person’s own immune system fight cancer.

About personalised cancer immunotherapy
The aim of personalised cancer immunotherapy (PCI) is to provide individual patients with treatment options that are tailored to their specific needs. The Roche PCI research and development programme comprises more than 20 investigational candidates, nine of which are in clinical trials. All studies include the prospective evaluation of biomarkers to determine which people may be appropriate candidates for Roche medicines. In the case of Tecentriq, PCI begins with the PD-L1 (programmed death ligand-1) IHC assay based on the SP142 antibody developed by Roche Tissue Diagnostics. The goal of PD-L1 as a biomarker is to identify those people most likely to experience clinical benefit with Tecentriq as a single agent versus those who may benefit more from combination approaches; the purpose is to inform treatment strategies which will give the greatest number of patients a chance for transformative benefit. The ability to combine Tecentriq with multiple chemotherapies may provide new treatment options to people across a broad range of tumours regardless of their level of PD-L1 expression.

PCI is an essential component of how Roche delivers on the broader commitment to personalised healthcare.

On June 4, 2016 Juno Therapeutics, Inc. (NASDAQ: JUNO), a biopharmaceutical company focused on re-engaging the body’s immune system to revolutionize the treatment of cancer, reported that its investigational chimeric antigen receptor (CAR) T cell product candidates are demonstrating encouraging clinical outcomes for adults and children with B-cell malignancies (Press release, Juno, JUN 4, 2016, View Source;p=RssLanding&cat=news&id=2175102 [SID:1234513025]). Data will be presented at the 52nd Annual Meeting of the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago, including an oral presentation today on JCAR014 (Abstract #102, Hall D1, 8:48 a.m. CT) and a poster presentation tomorrow on JCAR017 (Abstract #3048, Hall A, Board #370, 8:00 a.m. CT).
"We are encouraged by the continued efficacy and duration of response that we are seeing with our defined cell products in patients with B cell malignancies. We are moving rapidly to start potential registration trials for JCAR017 across a range of B cell malignancies, including ALL, NHL, and CLL," said Mark J. Gilbert, M.D., Juno’s Chief Medical Officer. "As our understanding of JCAR017 and JCAR014 evolves, we are increasingly able to study these defined cell product candidates in the outpatient setting, which may allow for greater access to our technologies over time."
JCAR014
Updated results from a randomized Phase I/II study examining JCAR014 in patients with relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), and chronic lymphocytic leukemia (CLL) will be presented today by Cameron Turtle, MBBS, Ph.D., of the Fred Hutchinson Cancer Research Center. Key data include:
In efficacy-evaluable ALL patients (N=34), complete remission was reported in 34/34 (100%) patients and complete molecular remission as measured by flow cytometry (CmR) was achieved in 32/34 (94%) patients. Additionally, 13/20 (65%) had a complete molecular remission as measured by the highly sensitive technique of IGH deep sequencing. In the cohort that received fludarabine/cyclophosphamide (Flu/Cy) lymphodepletion, 22/22 (100%) patients achieved a complete remission, all of which were a CmR. Median disease free survival (DFS) and overall survival (OS) have not yet been reached with patients followed for up to 18 months. Severe cytokine release syndrome (sCRS) was observed in 14/36 (39%) patients and Grade 3 or higher neurotoxicity was observed in 14/36 (39%) patients.
In patients with multiple NHL histologies (N=20), predominantly diffuse large B-cell lymphoma, who received Flu/Cy lymphodepletion followed by JCAR014 dose level 2 (2×106/kg), 16/20 (80%) had an overall response (OR), of which 10/20 (50%) experienced a complete response (CR). CRs continue in 70% of patients, ranging from 3 to 11+ months. sCRS was observed in 2/20 (10%) patients and Grade 3 or higher neurotoxicity was observed in 2/20 (10%) patients. Notably, 16/20 (80%) patients treated with Flu/Cy lymphodepletion followed by JCAR014 dose level 2 were treated in the outpatient setting, and 6/20 (30%) did not require hospitalization during the first 30 days of treatment.
A total of 13 high-risk CLL patients (complex karyotype, del17p, ibrutinib-refractory, ibrutinib-intolerant) received JCAR014 and either non-Flu/Cy (n=2) or Flu/Cy (n=11) lymphodepleting chemotherapy. In the Flu/Cy patients, OR rate was 10/11 (91%) patients, of which 5/11 (45%) patients achieved CR. CRs are ongoing in 100% of these patients with a range of 3 to 19+ months. sCRS was observed in 3/13 (23%) patients and Grade 3 or higher neurotoxicity was observed in 3/13 (23%) patients.
JCAR017
In addition to the adult JCAR014 data presented today, Rebecca Gardner, M.D., of Seattle Children’s, announced results from Seattle Children’s Phase I study of JCAR017 in pediatric and young adults with CD19+ r/r ALL (n=42) demonstrating 39/42 (93%) patients experienced a complete remission, all of which were a CmR by flow cytometry. In patients who received the Flu/Cy preconditioning regimen, 14/14 (100%) achieved a complete remission and a CmR. sCRS was observed in 10/42 (24%) patients and Grade 3 or higher neurotoxicity was observed in 10/42 (24%) patients.
About Juno’s Chimeric Antigen Receptor (CAR) and T Cell Receptor (TCR) Technologies
Juno’s CAR and TCR technologies genetically engineer T cells to recognize and kill cancer cells. Juno’s CAR T cell technology inserts a gene for a particular CAR into the T cell, enabling it to recognize cancer cells based on the expression of a specific protein located on the cell surface. Juno’s TCR technology provides the T cells with a specific T cell receptor to recognize protein fragments derived from either the surface or inside the cell. When either type of engineered T cell engages the target protein on the cancer cell, it initiates a cell-killing response against the cancer cell. JCAR014 and JCAR017 are investigational product candidates and their safety and efficacy have not been established.

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On June 4, 2016 Juno Therapeutics, Inc. (NASDAQ: JUNO), a biopharmaceutical company focused on re-engaging the body’s immune system to revolutionize the treatment of cancer, reported that encouraging clinical data from JCAR015, a chimeric antigen receptor (CAR) T cell product candidate, support its strategic approach towards the commercialization of its first CAR T therapy (Press release, Juno, JUN 4, 2016, View Source;p=RssLanding&cat=news&id=2175107 [SID:1234513024]). Updated results will be presented today in an oral presentation at the 52nd Annual Meeting of the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago (Abstract #7003, Arie Crown Theater, 4:00 p.m. CT).
"The ongoing efficacy and duration of response for a large percentage of patients, specifically those who do not go on to stem cell transplant, continues to be impressive," said Mark J. Gilbert, M.D., Juno’s Chief Medical Officer. "These findings provide us with further confidence about our development strategy and the ongoing Phase II ROCKET pivotal trial."
In the Phase I study, presented by lead investigator Jae H. Park, M.D., of Memorial Sloan Kettering Cancer Center, 51 adult patients with relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL) were treated with either cyclophosphamide or fludarabine/cyclophosphamide followed by an infusion of JCAR015. At the time of treatment, 31 patients had morphologic disease burden and 20 patients had minimal disease burden. Median study follow-up was 8.5 months. Key results include:
Complete response (CR) was observed in 23/30 (77%) patients with morphologic disease and in 18/20 (90%) patients with minimal disease.
In patients who achieved a CR and had adequate evaluation for minimal residual disease by flow cytometry or polymerase chain reaction, complete molecular remission was observed in 19/21 (90%) patients with morphologic disease and in 14/18 (78%) patients with minimal disease.
Median overall survival (OS) for patients with minimal disease treated with JCAR015 was not reached, and that for morphologic patients treated with JCAR015 was 9 months; median OS follow-up for all patients was 13 months.
Durable responses and survival observed in patients who received JCAR015 were comparable between groups that received a subsequent stem cell transplant and those that did not.
Severe cytokine release syndrome (sCRS) was observed in 14/51 (27%) patients and Grade 3 or higher neurotoxicity was observed in 15/51 (29%) patients. For patients with minimal disease, 1/20 (5%) patients experienced sCRS and 4/20 (20%) patients had Grade 3 or higher neurotoxicity.
About Juno’s Chimeric Antigen Receptor (CAR) and T Cell Receptor (TCR) Technologies
Juno’s CAR and TCR technologies genetically engineer T cells to recognize and kill cancer cells. Juno’s CAR T cell technology inserts a gene for a particular CAR into the T cell, enabling it to recognize cancer cells based on the expression of a specific protein located on the cell surface. Juno’s TCR technology provides the T cells with a specific T cell receptor to recognize protein fragments derived from either the surface or inside the cell. When either type of engineered T cell engages the target protein on the cancer cell, it initiates a cell-killing response against the cancer cell. JCAR015 is an investigational product candidate and its safety and efficacy have not been established.

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On June 4, 2016 Foundation Medicine, Inc. (NASDAQ:FMI) and AstraZeneca reported that they have entered into a definitive agreement to develop a novel companion diagnostic assay for Lynparza (olaparib) to support its global development program (Press release, Foundation Medicine, JUN 4, 2016, View Source [SID:1234513019]). The companion diagnostic will enable physicians to identify those patients most likely to benefit from AstraZeneca’s first-in-class poly ADP-ribose polymerase (PARP) inhibitor.

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Lynparza is an innovative, oral PARP inhibitor that exploits tumor DNA repair pathway deficiencies to preferentially kill cancer cells. This mode of action gives olaparib the potential for activity in a range of tumor types with DNA repair deficiencies. Lynparza is approved in the US for the treatment of patients with germline BRCA-mutated advanced ovarian cancer and in the European Union for patients with platinum-sensitive relapsed BRCA-mutated high-grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer.

Under the terms of the agreement, Foundation Medicine will develop and make available a regulatory approved product utilizing the Quality Systems Regulations (QSR)-compliant version of its FoundationOne comprehensive genomic profiling platform. This assay will detect multiple classes of genomic alterations across a range of genes involved in Homologous Recombination Repair (HRR). The assay, based on a scientifically selected panel of genes known to be involved in driving the HRR process, will be developed alongside the clinical program for Lynparza, as part of a coordinated drug-diagnostic regulatory strategy.

Nina Mojas, global medicine lead for Lynparza at AstraZeneca said, "This agreement supports the broad development program for our first-in-class PARP inhibitor, Lynparza. Utilizing Foundation Medicine’s leading capabilities in molecular information will help our work to assess the potential of the medicine to address unmet patient need across a number of cancers driven by DNA repair deficiencies, including and – significantly – beyond the BRCA mutations."

"Following our new master collaboration agreement with AstraZeneca, we are pleased to launch this first strategic initiative to support and advance the development of Lynparza in a number of cancers," stated Steven J. Kafka, Ph.D., president and chief operating officer for Foundation Medicine. "The work we’ve undertaken with AstraZeneca underscores the importance and potential of utilizing our rigorously validated, comprehensive profiling approach to make available to physicians an FDA-approved universal companion diagnostic solution for use with targeted medicines."

On June 4, 2016 Foundation Medicine, Inc. (NASDAQ:FMI) reported new critical genomics data at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2016 demonstrating the clinical significance of comprehensive genomic profiling (CGP) with FoundationOne in identifying patients with advanced lung cancer most likely to respond to RET inhibitor targeted therapies and also to predict those patients likely to develop resistance to targeted therapy (Press release, Foundation Medicine, JUN 4, 2016, View Source [SID:1234513018]).

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Key Data Highlights:

The poster titled, "MDM2 amplification (Amp) to mediate cabozantinib resistance in patients (Pts) with advanced RET-rearranged lung cancers," presented by Romel Somwar, Ph.D., senior research scientist, pathology, Memorial Sloan Kettering Cancer Center, analyzes the genomic profiles of patients treated with the RET inhibitor, cabozantinib, to better understand the molecular mechanisms that underlie intrinsic and secondary resistance. Key study findings include:

Comprehensive genomic profiles were performed on 3,842 lung cancer patients, detecting concurrent MDM2 amplification in 20 percent of tumors with RET fusions
In RET-rearranged cell lines and xenografts treated with cabozantinib and the MDM2 inhibitors, AMG232 and RG7388, a combination of cabozantinib and AMG232 proved more effective at suppressing tumor growth than either agent alone
The study shows that MDM2 amplification is a potential mechanism of primary or acquired resistance to cabozantinib, and therefore MDM2 inhibitors might be studied clinically to prevent the development of acquired resistance and enable longer, more durable responses to treatment
The second poster presentation titled, "Significant systemic and CNS activity of RET inhibitor vandetanib combined with mTOR inhibitor everolimus in patients with advanced NSCLC with RET fusion," by Tina Cascone, M.D., Ph.D. and Vivek Subbiah, M.D., from The University of Texas MD Anderson Cancer Center, demonstrates that targeted combination therapy of vandetanib with the mTOR inhibitor, everolimus, was tolerable and demonstrated significant activity in RET rearranged NSCLC. Key study findings include:

Vandetanib and everolimus were administered to 13 stage IV NSCLC patients, including six patients with tumors harboring RET fusions
All six patients with RET fusions experienced a response, including five partial responses and one patient with stable disease
The six patients with RET fusions were identified using CGP with FoundationOne. Notably, two additional patients tested positive for RET fusions using FISH and did not respond to treatment.
The study suggests that combination therapy was superior to monotherapy with RET inhibitors, warranting further studies of this combination. The study further highlights the superior accuracy of CGP for calling fusions over traditional single gene tests, like FISH.
"By helping us better understand the likelihood of response and resistance to certain therapies, CGP is providing information that can help improve physician treatment decisions and ultimately, we believe, lead to better patient outcomes," said Vincent Miller, M.D., chief medical officer, Foundation Medicine. "Additionally, the sensitivity and accuracy of FoundationOne to reliably detect all classes of clinically relevant alterations in non-small cell lung cancer allow us to circumvent the false positives that often arise with single gene and standard hotspot testing. As this study shows, inaccuracies in genomic testing can lead to unnecessary and often unsuccessful treatments, as well as inefficient and costly care delivery."

Genomic alterations in the RET gene are found in several different types of cancer. RET gene fusions occur in 1 percent of non-small cell lung cancers (NSCLC) and are well-established oncogenic drivers. The RET inhibitor agents, vandetanib and cabozantinib, have demonstrated antitumor activity in NSCLC patients harboring RET fusions, although data suggest that objective responses are observed in only a minority of patients, and progression-free survival (PFS) is shorter than with other oncogene targeted therapies in this disease. A portion of tumors may harbor intrinsic resistance to RET inhibitors, while some respond but eventually progress, yielding to the development of secondary resistance. However, molecular mechanisms that underlie resistance to cabozantinib are poorly understood. Taken together, these studies reinforce the critical importance of FoundationOne in identifying patients likely to respond to targeted therapies and to predict those patients likely to develop resistance.

Lung cancer is by far the leading cause of death among both men and women; about 1 out of 4 cancer deaths are from lung cancer1. There are two major types of lung cancer: NSCLC and small cell lung cancer (SCLC). NSCLC is the most common and accounts for approximately 85 percent of all lung cancer cases2. The American Cancer Society estimates there will be about 224,390 new cases of lung cancer in the United States for 2016 and about 158,080 deaths1.