On June 08, 2016 Immune Design (Nasdaq:IMDZ), a clinical-stage immunotherapy company focused on oncology, reported updated results from clinical trials of three immuno-oncology product candidates demonstrating promising and potentially clinically meaningful anti-tumor immune responses for Immune Design’s lead products (Press release, Immune Design, JUN 8, 2016, View Source [SID:1234513139]). This includes data presented at the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting and involves Immune Design’s two distinct immunotherapy applications — the ‘Specific Antigen’ and ‘Endogenous Antigen’ Approaches.

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"The data reflect single agent Phase 1 studies and provide strong rationale for continued development, including our ongoing randomized Phase 2 studies," said Carlos Paya, M.D., Ph.D., President and Chief Executive Officer. "We believe both of our approaches are disruptive and have the potential to impact the immunotherapy treatment landscape."

LV305 & CMB305: Specific Antigen Approach Targeting NY-ESO-1 Positive Tumors — Emerging Profile of Prolonged Survival Benefit

LV305 Phase 1 single agent trial completed in 24 patients with advanced or metastatic sarcoma cancers expressing NY-ESO-1 (ASCO abstract #3093)
Median overall survival (OS) has not been reached. One-year survival is 81%.
Median progression free survival (PFS) is 4.6 months.
14 patients (58%) had clinical benefit: One patient (4%) had a late-onset partial response and 13 patients (54%) had stable disease.
7/11 patients with pretreatment progressive disease (PD) had SD or PR following LV305.
Safety profile is very favorable, with only Grade 1/2 adverse effects (AEs).
CMB305 Phase 1 single agent trial ongoing in patients with NY-ESO-1 positive soft tissue sarcomas (preliminary analysis of first 14 patients)
Median OS has not been reached. 93% (13/14 patients) survival to date.
Median PFS is 5.5 months.
Best response to date is stable disease (10/14, 71%)
Safety profile is very favorable, with only Grade 1/2 AE
G100: Intratumoral Immune Activation Approach: Transforming "cold" tumors to "hot" tumors

G100 single agent and in combination with radiation in patients with Merkel cell carcinoma (ASCO Abstract #3021)
In final results from 10 patients, G100 produced a 50% overall response rate (ORR) per protocol, including a pathologic complete response (CR) following single agent G100 alone.
Four patients remain relapse-free in long-term follow up (range 13+ to 27.5+ months).
Analysis of the tumor microenvironment (TME) in G100-treated patients demonstrates the transformation of a "cold" to a "hot" tumor: increase of innate immune molecules that favor immune cell chemotaxis; increased NK cells and M1 macrophage markers; and dendritic cell antigen presentation. In addition, trafficking of CD4 and CD8 T cells from the stroma into the tumor bed was observed.
These changes in the TME were most prominent in the G100 responding patients.
No treatment-related AEs where observed; all AEs were grade 1/2.

On June 8, 2016 Kite Pharma, Inc. (Nasdaq:KITE) ("Kite"), a clinical-stage biopharmaceutical company focused on developing engineered autologous T-cell therapy (eACT) products for the treatment of cancer, reported three oral presentations relating to its clinical programs will be delivered at the upcoming 2016 European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress in Copenhagen, Denmark, June 9-12, 2016 (Press release, Kite Pharma, JUN 8, 2016, View Source [SID:1234513140]).

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"We are excited to showcase the progress we have made with personalized T-cell immuno-oncology for people with refractory lymphoma and to share our understanding of the outcomes for this patient population who have limited or no treatment options," said Arie Belldegrun, M.D., FACS, Chairman, President, and Chief Executive Officer of Kite. "These data are important to advance our novel breakthrough personalized treatments and ultimately address critical unmet medical needs."

Updated data from Phase 1 of Kite’s ZUMA-1 study of KTE-C19 in patients with chemorefractory non-Hodgkin lymphoma (NHL) will be presented in an oral presentation. An additional oral presentation will feature data from the SCHOLAR-1 study, the first and largest meta-analysis of outcomes in patients with chemorefractory diffuse large B-cell lymphoma (DLBCL), an aggressive and common form of NHL that is difficult to treat. Patients with chemorefractory DLBCL have not responded to prior treatment with chemotherapy or have relapsed within a year after autologous stem cell transplantation.

Data from a Phase 1-2a study evaluating anti-CD19 CAR T-cell therapy after low-dose chemotherapy in people with advanced lymphoma will also be highlighted in an oral presentation. This study is being conducted as part of a Cooperative Research and Development Agreement (CRADA) between Kite and the National Cancer Institute (NCI).

Kite also recently announced that the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) and Committee for Advanced Therapies (CAT) has granted access to its newly established Priority Medicines (PRIME) regulatory initiative for KTE-C19 in the treatment of patients with refractory DLBCL. PRIME provides early and enhanced regulatory support to optimize regulatory applications and speed up the review of medicines that address a high unmet need. KTE-C19 is an investigational therapy in which a patient’s T cells are genetically modified to express a chimeric antigen receptor (CAR) designed to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias.

Oral presentations at the 2016 EHA (Free EHA Whitepaper) Annual Congress:

Results from SCHOLAR-1: Outcomes in patients with refractory aggressive diffuse large B-cell lymphoma (DLBCL)

Date: Saturday, June 11, 2016, 5:00 – 5:15 PM CEST
Location: Hall A1
Abstract Number: S481
Presenter: Christian Gisselbrecht, M.D., The Lymphoma Academic Research Organisation (LYSARC), Pierre-Bénite, France

Updated results from ZUMA-1: A phase 1-2 multicenter study evaluating the safety and efficacy of KTE-C19 (anti-CD19 CAR T cells) in refractory aggressive B-cell Non-Hodgkin Lymphoma (NHL)

Date: Sunday, June 12, 2016, 8:45 – 9:00 AM CEST
Location: Hall A1
Abstract Number: S791
Presenter: Tanya Siddiqi, M.D., City of Hope National Medical Center, Duarte, CA

Low-dose chemotherapy followed by anti-CD19 chimeric antigen receptor (CAR) T cells induces remissions in patients with advanced lymphoma

Date: Sunday, June 12, 2016, 9:00 – 9:15 AM CEST
Location: Hall A1
Abstract Number: S792
Presenter: Stephanie L. Goff, M.D., Surgery Branch, Center for Cancer Research, The National Cancer Institute, Bethesda, MD

About Kite’s ZUMA Clinical Programs for KTE-C19

KTE-C19 is an investigational therapy in which a patient’s T cells are genetically modified to express a CAR that is designed to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias. Kite is currently enrolling four pivotal studies (also known as ZUMA studies) for KTE-C19 in patients with various B-cell malignancies.

Study Phase Indication Status
ZUMA-1
NCT02348216 Phase 2 Pivotal
(N=112) Chemorefractory DLBCL, PMBCL, TFL Phase 2 enrolling
ZUMA-2
NCT02601313 Phase 2 Pivotal
(N=70) Relapsed/refractory MCL Phase 2 enrolling
ZUMA-3
NCT02614066 Phase 1/2 Pivotal
(N=75) Relapsed/refractory Adult ALL Phase 1/2 enrolling
ZUMA-4
NCT02625480 Phase 1/2 Pivotal
(N=75) Relapsed/refractory Pediatric ALL Phase 1/2 enrolling

DLBCL = diffuse large B-cell lymphoma
PMBCL = primary mediastinal B-cell lymphoma
TFL = transformed follicular lymphoma
MCL = mantle cell lymphoma
ALL = acute lymphoblastic leukemia

On June 8, 2016 AstraZeneca reported it has entered into a commercialisation agreement with Aspen Global Incorporated (AGI), part of the Aspen Group, for rights to its global anaesthetics portfolio outside the US (Press release, AstraZeneca, JUN 8, 2016, View Source [SID:1234513247]). The agreement covers seven established medicines – Diprivan (general anaesthesia), EMLA (topical anaesthetic) and five local anaesthetics (Xylocaine/Xylocard/Xyloproct, Marcaine, Naropin, Carbocaine and Citanest).

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Under the terms of the agreement, AGI will acquire the commercialisation rights, outside the US, to AstraZeneca’s portfolio of anaesthetic medicines for an upfront consideration of $520 million. Additionally, AGI will pay AstraZeneca up to $250 million in a Product Sales-related payment, as well as double-digit percentage trademark royalties on Product Sales. AstraZeneca will manufacture and supply the products on a cost plus basis to AGI for an initial period of 10 years. Upon completion, Aspen will assume responsibility for all activities relating to the sale of the portfolio in all relevant markets.

Pascal Soriot, Chief Executive Officer, AstraZeneca, said: "AstraZeneca has a rich heritage in anaesthetic medicines and this agreement will extend the reach of our established portfolio to a greater number of patients through AGI’s extensive commercial network. This agreement supports our strategic focus on the new medicines in three main therapy areas."

Stephen Saad, Group Chief Executive, Aspen, said: "This is a strategically-important investment for AGI and it is pleasing to have a company such as AstraZeneca recognise Aspen’s commercial competencies. This transaction is an excellent opportunity to build on the quality brands commercialised through AGI, working alongside an acknowledged pioneer and leader in the field of anaesthetics."

AstraZeneca’s portfolio of anaesthetics is available in over a hundred countries worldwide, including key markets such as China, Japan, Australia and Brazil. The portfolio continues to generate stable revenue, with global Product Sales in 2015 of $592 million. The US rights to the products were divested to Abraxis, now part of Fresenius Kabi, in 2006.

Financial considerations

The transaction is subject to customary closing conditions and is anticipated to complete in the third quarter of 2016. AstraZeneca will retain a significant ongoing interest in the anaesthetics portfolio through ongoing milestone and royalty payments and the manufacture and supply of the products to Aspen. The upfront and milestone payments, as well as royalty receipts, which are open-ended, will therefore be reported as Externalisation Revenue in the Company’s financial statements. The agreement will not impact the Company’s financial guidance for 2016.

On June 7, 2016 Agendia, Inc., a world leader in personalized medicine and molecular cancer diagnostics, reported that it has presented new prospective data for its MammaPrint 70-gene breast cancer recurrence assay at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois (Press release, Agendia, JUN 7, 2016, View Source [SID:1234513121]).

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Results from the Prospective study Of MammaPrint in breast cancer patients with an Intermediate recurrence Score (PROMIS) show that MammaPrint can provide clear guidance on whether a patient should receive chemotherapy, compared to the indeterminate results from 21-gene assay (OncotypeDx). MammaPrint provides a definitive, binary High or Low Risk result for a patient’s cancer recurring and thus whether the patient needs more aggressive, or less aggressive therapy.

Between 38-67% of women tested in different studies using the 21-gene assay were classified as having an intermediate/indeterminate Recurrence Score (between 18 and 30).1 PROMIS evaluated 840 estrogen receptor (ER)-positive, lymph node (LN) positive or LN negative women across 58 US institutions who had previously received an intermediate/indeterminate risk score from the 21-gene assay. Patient samples were re‑tested using MammaPrint to refine the risk classification and provide additional treatment guidance.

Of the 840 intermediate risk patients, MammaPrint reclassified 55% (466) of these patients as High Risk and 45% (374) as Low Risk of the individual’s cancer recurring. No correlation between definitive MammaPrint results or the indeterminate 21-gene assay Recurrence Score could be identified, reinforcing the discordance between these assays and inability to use the results interchangeably. MammaPrint was shown to provide additional prognostic information independent from clinicopathological factors to support the treatment decision.

Based on the outcome of the MammaPrint test, 34% (282/840) of physicians changed their treatment decisions, preventing both under and over treatment: 37% (171/466) of the high risk patients had chemotherapy added to their treatment recommendation and 29% (108/374) of the low risk patients had chemotherapy removed from their treatment recommendation. Of the MammaPrint Low Risk patients who were previously indicated to receive chemotherapy based on the 21-gene assay results, 76% of patients (108/142) decided to forego chemotherapy, preventing unnecessary overtreatment in this group.

Medical oncologist Dr. Michaela Tsai from the Virginia Piper Cancer Center, Minneapolis, MN and primary author of the PROMIS poster commented, "Of 466 intermediate patients reclassified as High Risk by MammaPrint, 342 have an Recurrence Score ≤25 and were not recommended for chemotherapy by St. Gallen Guidelines (Goldhirsch, Winer et al. 2013), risking up to a 73% chance of under-treatment." She also noted, "79% of physicians reported that they had greater confidence in their treatment recommendations with MammaPrint."

Dr. William Audeh, Chief Medical Officer of Agendia said: "The clinical performance of MammaPrint and its ability to accurately inform and guide treatment decisions has been definitively proven by the recent presentation of the MINDACT trial at the 2016 AACR (Free AACR Whitepaper) meeting. This unique phase III prospective, randomized, controlled study provides the highest level of clinical evidence to MammaPrint above any other genomic assay for making adjuvant therapy decisions in early-stage breast cancer."

MINDACT included 6,693 patients and is a phase III, prospective, randomized controlled, clinical trial comparing the use of MammaPrint 70-gene assay with clinicopathological criteria (current standard of care) for selecting early-stage breast cancer patients who should be treated with adjuvant chemotherapy.

"The PROMIS trial showed the positive impact a binary test could have in the clinical setting by providing a clear risk assessment of the patient to physicians" said Mark Straley, Chief Executive Officer at Agendia. "MammaPrint is the only FDA-cleared assay for early-stage breast cancer patients of all ages, further validating the quality and clinical utility of the test."

1 Lo, Mumby et al. 2011, Sulayman, Spellman et al. 2012, Stemmer, Klang et al. 2013, Sparano, Grey et al. 2015

On June 7, 2016 Transgenomic, Inc. (TBIO), (NASDAQ: TBIO), reported that it is unveiling new data at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2016 Annual Meeting further confirming the utility, speed and efficiency of its ICE COLD-PCR (ICP) technology for liquid biopsy detection of tumor mutations (Press release, Transgenomic, JUN 7, 2016, View Source [SID:1234513122]). The company is distributing a new educational handout at the meeting highlighting expanded concordance data showing that ICP plasma-based liquid biopsies detect all of the mutations identified using conventional tissue samples and also detect additional tumor alterations missed by conventional methods. Another educational handout presents data showing how use of ICP with Thermo Fisher’s Veriti thermal cycler expedites the testing of liquid biopsy samples, producing accurate results rapidly and efficiently.

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TBIO President and CEO Paul Kinnon commented, "As the highest profile cancer meeting of the year, ASCO (Free ASCO Whitepaper) is an excellent venue for presenting our expanded concordance study data further confirming the accuracy and superior performance of ICE COLD-PCR liquid biopsies for tumor detection and monitoring. We also are unveiling new study data highlighting the speed and efficiency of our ICP enrichment technology when used with a leading thermal cycler. We believe ICP’s accuracy, versatility and ease of use have the potential to enable wide adoption of routine genomic testing in cancer research and patient care, and the new data we are discussing at ASCO (Free ASCO Whitepaper) further supports the technology’s near-term clinical and commercial potential."

At the ASCO (Free ASCO Whitepaper) meeting, Transgenomic is distributing an educational report, "CRC Concordance Update – Stage IV CRC Sample Analysis with ICE COLD-PCRTM," which describes the results of an expanded concordance study assessing the ability of its multiplexed ICE COLD-PCR technology to detect a key tumor mutation in matched plasma samples compared to detection in the same patients using tissue and plasma samples analyzed using conventional Sanger sequencing methods. The expanded study included 32 patients with late stage colorectal cancer. Use of ICP-enriched testing resulted in an overall 96.9% concordance rate, with a 94.7% concordance rate for the mutation positive samples. In addition, actionable mutations were detected in two patient samples analyzed using ICP-enriched methods that were missed using conventional PCR with Sanger sequencing. Notably, the missed mutations were detected by ICP in both the plasma and tissue samples from these patients.

The researchers conclude that the high concordance rates achieved in the study and the ability of the ICP-enriched approach to detect relevant mutations missed by conventional methods support the clinical validity and utility of ICP-based liquid and tissue biopsies for mutation detection and monitoring in cancer patients.

Anil Vachani, MD, MS, Associate Professor of Medicine at the Hospital of the University of Pennsylvania and the Veteran’s Administration Medical Center and an investigator working with TBIO, commented, "The ability to accurately and efficiently detect tumor mutations from non-invasive blood-based patient samples is essential for realizing the potential of precision medicine approaches to transform cancer treatment. I welcome studies that increase our confidence in the validity of new technologies such as ICE COLD-PCR to help enable use of targeted and other precision treatment approaches."

A second TBIO educational handout, "Simple and Effective Clinical Testing Protocol Using ICE COLD-PCRTM across Targeted Cancer Gene Panels using the Veriti Thermal Cycler and Sanger Sequencing," details a new study that demonstrates how combining multiplexed ICE COLD-PCR with the Thermo Fisher Veriti thermal cycler expedites mutation detection and monitoring using liquid biopsy samples. It shows that with the Veriti thermal cycler, ICE COLD-PCR amplifications can be grouped based on temperature and primer annealing parameters to enable multiple amplicon enrichments in a single thermal cycler run. By combining the flexibility of the Veriti thermal cycler, the superior enrichment power of ICP and the rapid turnaround time of Sanger sequencing, liquid biopsy test results were generated in about four days, compared to total turnaround times of about four weeks for conventional tissue biopsies. Rapid results are an important advantage in cancer clinical testing and patient monitoring, where critical patient treatment decisions increasingly rely on up-to-date genomic data.

The study researchers note too that these results provide an opportunity for molecular diagnostic laboratories to reevaluate the use of Sanger sequencing for confirmation of mutation detection results from next-generation sequencing (NGS) platforms, and point out that by using this protocol, Sanger platforms can also be re-considered for front line mutation detection, with the potential to produce accurate results more rapidly and cost effectively than NGS platforms.

ICE COLD-PCR achieves its ultra-high sensitivity through selective amplification of mutant DNA. The result is up to a 500-fold increase in sensitivity in identifying mutations with the most precise sequence alteration detection rates available. ICP was originally developed by the laboratory of Dr. Mike Makrigiorgos at the Dana-Farber Cancer Institute, which has exclusively licensed rights to the technology to Transgenomic.