On June 4, 2016 Genus Oncology reported that it collaborates with leaders in leukemia research at Harvard’s Dana-Farber Cancer Institute and Beth Israel Deaconess Medical Center on an investigator-initiated Phase 1b/2a trial of GO-203 in combination with Decitabine for the treatment of patients with relapsed/refractory AML (Press release, Genus Oncology, JUN 4, 2016, View Source [SID:SID1234515226]).

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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 ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) reported updated clinical data on its investigational tyrosine kinase inhibitor (TKI), brigatinib, in patients with anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer (NSCLC) from an ongoing Phase 1/2 trial (Press release, Ariad, JUN 4, 2016, View Source;p=RssLanding&cat=news&id=2175095 [SID:1234512986]). The current results include more mature efficacy and safety data for brigatinib, including updated response rates and median duration of response in ALK+ NSCLC patients.

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The updated Phase 1/2 results are being presented today at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting in Chicago.

Phase 1/2 Study

The data presented at ASCO (Free ASCO Whitepaper) include safety analyses on all patients in the trial (n=137) and efficacy analyses on all patients with ALK+ NSCLC (n=79). Of the 79 ALK+ NSCLC patients, all but eight had failed prior crizotinib. The presentation is based on patient data as of November 2015 with a median time on treatment for ALK+ NSCLC patients of 17.0 months (range, 0.03 – 44.4 months, ongoing). Patient enrollment in the trial is complete, with the last patient enrolled in July 2014.

"The long-term follow up on this clinical trial of brigatinib shows substantial anti-tumor activity with an objective response rate of approximately 72 percent in crizotinib-resistant ALK-positive NSCLC patients," stated D. Ross Camidge, M.D., Ph.D., director of thoracic oncology at the Colorado University Cancer Center. "The median progression-free survival in this post-crizotinib patient group exceeds one-year and has not yet been reached in patients not previously treated with crizotinib. Importantly, no new safety signals have emerged at this later time of follow up."

Key data from the study include:

Anti-tumor Activity of Brigatinib in ALK+ NSCLC Patients

Of the 71 ALK+ NSCLC patients with prior crizotinib therapy, 51 (72%) demonstrated an objective response to brigatinib. Forty-four responses were confirmed (62%).
Of the 25 patients treated at the 180 mg dose regimen that included a seven-day lead-in dose of 90 mg, 20 (80%) demonstrated an objective response, of which 19 (76%) were confirmed.
Of the eight crizotinib-naive ALK+ NSCLC patients treated with brigatinib, all demonstrated an objective response (100%), including three complete responses (CR). All responses were confirmed.
The "waterfall plot" analysis demonstrated tumor shrinkage in nearly all ALK+ NSCLC patients, with 21 patients experiencing 100 percent shrinkage of the target lesions.
The median duration of response in confirmed responders was 14.5 months in ALK+ NSCLC patients treated with prior crizotinib therapy and was not yet reached in ALK+ NSCLC patients who were crizotinib-naive.
Median progression-free survival (PFS) was 12.9 months in ALK+ NSCLC patients with prior crizotinib therapy and was not yet reached in ALK+ NSCLC patients who were crizotinib-naive.
Overall survival (OS) at one year was 77 percent in patients who received prior crizotinib (projected 2-year OS was 63%) and 100 percent in patients who were crizotinib-naive (projected 2-year OS was 100%).

An evaluation of the efficacy of brigatinib in ALK+ NSCLC patients with intracranial CNS metastases at baseline was also included in the ASCO (Free ASCO Whitepaper) presentation. In an independent central review of brain magnetic resonance imaging (MRI) scans, 46 ALK+ NSCLC patients were evaluable for intracranial response, including 15 who had measurable intracranial CNS metastases at baseline, and 31 patients who had only non-measurable intracranial CNS metastases.
10 of 15 (67%) patients with measurable intracranial CNS metastases had an intracranial objective response, and 13 of 31 (42%) with only non-measurable intracranial CNS metastases had complete disappearance of intracranial lesions.
Median intracranial PFS for ALK+ NSCLC patients with intracranial CNS metastases at baseline was 15.6 months. Median duration of intracranial response in confirmed responders was 11.4 months.
Safety and Tolerability – All Patients Enrolled

The most common treatment-emergent adverse events (AEs; ≥ 30%), regardless of relationship to treatment, in all patients were nausea (51%), fatigue (42%), diarrhea (41%), headache (34%), and cough (33%).
Treatment-emergent AEs, regardless of relationship to treatment, grade 3 or higher, occurring in ≥4% patients were increased lipase (9%), dyspnea (7%), hypertension (5%), increased amylase (4%), and fatigue (4%)
Serious treatment-emergent AEs, regardless of relationship to treatment, occurring in three or more patients were dyspnea (7%), pneumonia (7%), hypoxia (5%), pulmonary embolism (3%), malignant pericardial effusion (2%), and pneumonitis (2%).
A subset of pulmonary AEs (including dyspnea, hypoxia, pneumonia and/or pneumonitis) was observed to occur within 7 days of treatment initiation or treatment re-initiation following a prolonged dose interruption. Most events occurred within 48 hours of dosing and were generally managed with dose interruption or discontinuation.
Rates of these AEs were numerically lower with lower starting doses (11/137 [8%], overall)
6/44 (14%) in patients started at 180 mg qd
1/50 (2%) in patients started at 90 mg qd
Among 32 patients treated with 90 mg qd for 7 days followed by 180 mg qd, no such events were reported after dose escalation
Administration of brigatinib at 180 mg with a 7-day lead-in at 90 mg appears to not be associated with an increased risk of additional early pulmonary AEs, when compared with continuous administration of brigatinib at 90 mg.
About Brigatinib

Brigatinib is an investigational, targeted cancer medicine discovered internally at ARIAD Pharmaceuticals, Inc. It is in development for the treatment of patients with anaplastic lymphoma kinase positive (ALK+) non-small cell cancer (NSCLC) whose disease is resistant to crizotinib. Brigatinib is currently being evaluated in the global Phase 2 ALTA trial that is anticipated to form the basis for its initial regulatory review. ARIAD has also initiated the Phase 3 ALTA 1L trial to assess the efficacy of brigatinib in comparison to crizotinib. More information on brigatinib clinical trials, including the expanded access program (EAP) can be found here.

On June 4, 2016 ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) reported clinical data from an analysis aimed at characterizing the activity of its investigational tyrosine kinase inhibitor (TKI), brigatinib, in patients with anaplastic lymphoma kinase positive (ALK+) advanced non-small cell lung cancer (NSCLC) who have progressed on crizotinib (Press release, Ariad, JUN 4, 2016, View Source;p=RssLanding&cat=news&id=2175096 [SID:1234512987]). The analysis was based on ALK mutation status as determined by next-generation sequencing (NGS) of tumor tissue collected from the ongoing Phase 1/2 and ALTA clinical trials.

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Data from this analysis showed that brigatinib yields confirmed responses in patients with multiple different secondary ALK mutations, including one G1202R case. There are no currently approved ALK treatments that have demonstrated activity against the G1202R mutation.

These data are being presented today at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting in Chicago.

Study Methods

Requirements for the Phase 1/2 and ALTA trials of brigatinib included that tumor tissue be collected at patient screening after failure on crizotinib therapy and prior to brigatinib treatment. An optional post-baseline tumor biopsy also was requested following disease progression on brigatinib. Tumor samples were analyzed using a NGS (next-generation sequencing) platform that examined the entire coding sequence of 315 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer. This analysis focuses on the relationship between brigatinib clinical activity and ALK mutation status at baseline and after disease progression on brigatinib therapy.

A total of 32 baseline tumor samples from the clinical trials of brigatinib were evaluable using NGS, and a total of six post-baseline samples following disease progression on brigatinib were evaluable by NGS.

Study Results

Of the 32 patients with baseline NGS data, 22 (69%) achieved a confirmed objective response on brigatinib.
Of the 9 patients with secondary ALK mutations at baseline, 7 (78%) achieved a confirmed objective response on brigatinib.
Of the 23 patients without secondary ALK mutations at baseline, 15 (65%) achieved a confirmed objective response rate (ORR) on brigatinib.

Of the 6 patients with evaluable tissue samples collected after progression on brigatinib therapy, 5 (83%) were determined to have detectable secondary mutations in the ALK kinase domain. Three out of five of these patients had complex mutation patterns, following responses lasting 5.4, 7.4 and 28.5 months. Two out of five had single secondary ALK kinase domain mutations detected, following responses lasting 10.9 and 11 months.
Of the one patient with a secondary G1202R mutation, the patient achieved a confirmed response on brigatinib and the response is on-going.

"It is encouraging that responses to brigatinib were observed in patients with crizotinib resistant ALK+ lung cancer with and without the presence of ALK resistance mutations. This is consistent with preclinical studies showing brigatinib to be a potent pan-inhibitor of all known ALK secondary resistance mutants," stated Scott N. Gettinger, M.D., associate professor of medicine at Yale Cancer Center.

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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