On November 9, 2017 Seattle Genetics, Inc. (Nasdaq: SGEN) reported that the U.S. Food and Drug Administration (FDA) has approved ADCETRIS (brentuximab vedotin) for the treatment of adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) and CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy (Press release, Seattle Genetics, NOV 9, 2017, View Source;p=RssLanding&cat=news&id=2315957 [SID1234521902]). Primary cutaneous ALCL and MF are the most common subtypes of cutaneous T-cell lymphoma (CTCL). The approval is based on data from the phase 3 ALCANZA trial and two phase 2 investigator-sponsored trials. The phase 3 ALCANZA study was designed to compare ADCETRIS monotherapy administered every three weeks versus physician’s choice of representative standard of care options, methotrexate or bexarotene. The trial met its primary endpoint with the ADCETRIS treatment arm demonstrating a highly statistically significant improvement in the rate of objective response lasting at least four months (ORR4) versus the control arm as assessed by an independent review facility. ORR4 was 56.3 percent (95% CI: 44.1, 68.4) in the ADCETRIS arm compared to 12.5 percent (95% CI: 4.4, 20.6) in the control arm (p-value <0.001). The most common adverse reactions (≥ 20 percent) were: anemia, peripheral sensory neuropathy, nausea, diarrhea, fatigue and neutropenia.

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This is the fourth FDA-approved indication for ADCETRIS, which also has: (1) regular approval for treatment of classical Hodgkin lymphoma (cHL) patients who fail autologous hematopoietic stem cell transplantation (auto-HSCT) or who fail at least two prior multi-agent chemotherapy regimens and are not auto-HSCT candidates, (2) regular approval for the treatment of patients with cHL at high risk of relapse or progression as post-auto-HSCT consolidation, and (3) accelerated approval for treatment of systemic anaplastic large cell lymphoma (sALCL) patients who fail at least one prior multi-agent chemotherapy regimen. Accelerated approval in the sALCL indication is based on overall response rate, and continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

In November 2016, the FDA granted ADCETRIS Breakthrough Therapy Designation (BTD) for the treatment of patients with pcALCL and CD30-expressing MF who require systemic therapy and have received one prior systemic therapy. The FDA also granted Priority Review for the supplemental Biologics License Application (BLA), and the Prescription Drug User Fee Act (PDUFA) target action date was December 16, 2017.

"Cutaneous T-cell lymphoma is a blood cancer of the skin with no known cure and few new treatment options. It is a disfiguring disease in dire need of more effective and durable treatment options to help keep this debilitating and painful disease at bay," said Susan Thornton, cutaneous lymphoma patient and chief executive officer of the Cutaneous Lymphoma Foundation (CLF). "As both a patient and representative of the cutaneous lymphoma community, we welcome the FDA approval of ADCETRIS as a new treatment option for the most common subtypes of cutaneous T-cell lymphoma in patients who require systemic therapy and we look forward to sharing this important milestone with patients and physicians."

"Our phase 3 ALCANZA clinical trial evaluating ADCETRIS in patients with primary cutaneous anaplastic large cell lymphoma and mycosis fungoides, which are the most common types of cutaneous T-cell lymphoma, demonstrated superior efficacy with durable responses for long-term disease management when compared to standard of care treatment options methotrexate and bexarotene," said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "These data, along with data from investigator-sponsored clinical trials, led to the FDA approval of ADCETRIS as a treatment for patients with pcALCL or CD30-expressing MF, which represent the most common subtypes of CTCL. This FDA approval, which was granted more than a month in advance of the PDUFA date, represents a significant milestone for the lymphoma community. Our goal is to establish ADCETRIS as the foundation of care in CD30-expressing lymphomas and this approval represents our fourth FDA-approved indication."

The FDA approval is based primarily on positive results from a phase 3 trial called ALCANZA that were presented at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December 2016 and published online in the Lancet in June 2017. Results from the ALCANZA trial in 128 pcALCL and CD30-expressing MF patients requiring systemic therapy included:

The trial achieved its primary endpoint with the ADCETRIS treatment arm demonstrating a highly statistically significant improvement in the rate of ORR4 versus the control arm as assessed by an independent review facility. ORR4, as assessed by Global Response Score, was 56.3 percent in the ADCETRIS arm compared to 12.5 percent in the control arm (p-value <0.001).
Key secondary endpoints specified in the protocol, including objective response rate, complete response rate and progression-free survival, were all highly statistically significant in favor of the ADCETRIS arm.
The objective response rate in the ADCETRIS arm was 67.2 percent (95% CI: 55.7, 78.7) compared to 20.3 percent (95% CI: 10.5, 30.2) in the control arm.
The CR rate in the ADCETRIS arm was 15.6 percent (95% CI: 7.8, 26.9) compared to 1.6 percent (95% CI: 0, 8.4) in the control arm (p-value = 0.0066).
The median PFS in the ADCETRIS arm was 16.7 months (95% CI: 14.9, 22.8) compared to 3.5 months (95% CI: 2.4, 4.6) in the control arm (HR 0.270; 95% CI, 0.169, 0.430; p-value <0.001).
The safety profile associated with ADCETRIS from the ALCANZA trial was generally consistent with the existing prescribing information. The most common adverse events occurring in 20 percent or more of patients of any grade include: anemia, peripheral sensory neuropathy, nausea, diarrhea, fatigue and neutropenia.
Additional data from two investigator-sponsored phase 2 trials evaluating ADCETRIS in 73 MF patients were also incorporated into the supplemental BLA representing a broader spectrum of CD30-expression levels than that of the ALCANZA trial.

About CTCL

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Cutaneous lymphomas are a category of non-Hodgkin lymphoma that primarily involve the skin. According to the Cutaneous Lymphoma Foundation, CTCL is the most common type of cutaneous lymphoma and typically presents with red, scaly patches or thickened plaques of skin that often mimic eczema or chronic dermatitis. The most common subtypes of CTCL include mycosis fungoides and primary cutaneous anaplastic large cell lymphoma. Progression from limited skin involvement may be accompanied by skin tumor formation, ulceration and exfoliation, complicated by itching and infections. Advanced stages are defined by involvement of lymph nodes, peripheral blood and internal organs.

According to the American Cancer Society and the Leukemia and Lymphoma Society, CTCL represents approximately four percent of non-Hodgkin lymphoma, which is about 2,800 patients. Not all newly diagnosed patients require systemic therapy. The standard treatment for systemically pretreated CTCL includes skin-directed therapies, radiation and systemic therapies. The systemic therapies currently approved for treatment have demonstrated 30 to 45 percent objective response rates, with low complete response rates.

On November 9, 2017 NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products, reported the highlights of numerous advances in understanding immune response and cancer immunotherapy using the nCounter platform that will be presented at the 32nd Annual Meeting of the Society of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (Press release, Ligand, NOV 9, 2017, View Source [SID1234521879]).

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"The scope of nCounter-based research being presented at this year’s SITC (Free SITC Whitepaper) conference demonstrates our scientific and commercial momentum in immuno-oncology," said Alessandra Cesano, chief medical officer of NanoString. "In addition, several abstracts outline the unique capabilities of our Digital Spatial Profiling technology to characterize the tumor and its microenvironment to inform cancer research and drug development."

At least 45 abstracts using NanoString’s nCounter platform will be presented at the SITC (Free SITC Whitepaper) Annual Meeting, being held in National Harbor, Maryland, Nov. 8-12, 2017. The research being presented spans a wide breadth of applications including biomarker development, assessing the biology of immune responsiveness and resistance, and digital pathology. They include biomarker studies covering 21therapeutic agents, as single agents or in combination.

Nineteen studies used NanoString’s PanCancer Series of panels to explore biomarkers associated with response to immunotherapy. Fourteen of these studies incorporate NanoString’s best-selling PanCancer Immune Profiling Panel. An additional five studies incorporating both early access and commercial versions of NanoString’s new PanCancer IO 360 Panel. The PanCancer IO 360 Panel assays key pathways from the tumor, the microenvironment and the immune system and includes more than 20 signatures that are potentially associated with therapeutic response to novel therapeutic agents with "matched" mechanisms of action. Three additional studies incorporate the nCounter Hallmarks of Cancer suite of gene expression panels, which includes three panels covering Cancer Immune Profiling, Cancer Pathways, and Cancer Progression.

The PanCancer IO 360 Panel studies provide initial evidence of positive association between the Tumor Inflammation Signature scores and clinical response to different immuno-oncology agents including nivolumab, ipilimumab, pembrolizumab and entinostat. NanoString’s Tumor Inflammation Signature (TIS) was recently described by Ayers, et al. (View Source) and is included in the PanCancer IO360 panel. The Tumor Inflammation Signature measures the presence or absence of a peripherally suppressed adaptive immune response within the tumor.

Five studies cover the use of NanoString’s Digital Spatial Profiling (DSP) platform in immuno-oncology research. DSP allows for digital quantification of protein from discrete regions of FFPE tissue in an automated and multiplex format. DSP will become widely available with the launch of a new instrument planned for late 2018, and in the meantime is available under a Technology Access Program.

Two studies cover the use of 3D Biology panels and demonstrate the utility of the nCounter platform. NanoString’s 3-D Flow technology provides detailed molecular profiles of T cell populations, and enables unique, simultaneous analysis of high-plex protein and RNA data. 3D Biology and 3D Flow approaches can be used to characterize baseline immunological state and response to stimulation, which may be useful for profiling mechanisms of action or therapeutic response.

At the 2017 SITC (Free SITC Whitepaper) Annual Meeting, NanoString will showcase its nCounter platform, IO360 Data Analysis, Digital Spatial Profiling and 3D Biology capabilities at booth #605.

NanoString will host a Digital Spatial Profiling Educational Session on Nov. 11, 2017, 12:45 – 1:45 p.m.

Below is a summary of abstracts co-authored by NanoString employees:

Abstract # Title Hyperlink
05 A dendritic cell targeting NY-ESO-1 vaccine significantly augments early and durable immune responses in melanoma patients pretreated with human Flt-3 Ligand View Source

019 ENCORE-601: Phase 1b/2 study of entinostat (ENT) in combination with pembrolizumab (PEMBRO) in patients with non-small cell lung cancer (NSCLC) View Source

P40 Deep proteomic and transcriptomic analysis of sorted T cells with a simple, integrated workflow View Source

P43 Assessment of Pharmacodynamic Effects of Immuno-Oncology Agents in Cynomolgus Monkeys using High-Content Gene Expression Profiling View Source

P64 Analytical Validation of Digital Spatial Profiling – a novel approach for multiplexed characterization of protein distribution and abundance in FFPE tissue sections View Source

P65 Spatially-resolved, multiplexed digital characterization of protein abundance in FFPE tissue sections: application in preclinical mouse models View Source

P66 Digital spatial profiling platform allows both spatially-resolved, multiplexed measurement of solid tumor and immune-associated protein distribution and abundance using a single FFPE tissue section View Source

P72 Analysis of biomarkers from a cohort of advanced melanoma patients previously exposed to immune checkpoint inhibition treated with entinostat (ENT) and pembrolizumab (PEMBRO).

View Source
P73 First-in-human neoadjuvant study of the immunogenomic impact of the oral IDO inhibitor epacadostat (INCB024360) on the tumor microenvironment of advanced ovarian cancer View Source

P98 Immunological profiling of baseline and resected biopsies from locally/regionally advanced/recurrent melanoma treated with neoadjuvant combination ipilimumab (3mg/kg or 10mg/kg) and high dose IFN-α2B View Source

P99 Biomarker analysis from the OpACIN trial (Neo-/adjuvant ipilimumab + nivolumab (IPI+NIVO) in palpable stage 3 melanoma) View Source

P100 Pretreatment gene expression correlation with clinical response to pembrolizumab or nivolumab in metastatic melanoma View Source

P383 Molecular and immune characterization of melanoma metastases with heterogeneous PTEN expression View Source

P485 Use of the NanoString Gene Expression Profiling Platform to Capture the Immunological Status of the Leukemia Microenvironment View Source

P512 Deep immunoprofiling of rare T-cell populations from clinical samples View Source

P524 Clinical and biomarker analyses of a phase II study of intratumoral tavokinogene telseplasmid (pIL-12) plus pembrolizumab in stage III/IV melanoma patients predicted to not respond to anti-PD-1 View Source

On November 9, 2017 Heron Therapeutics, Inc. (Nasdaq: HRTX) (the Company or Heron), a commercial-stage biotechnology company focused on developing novel, best-in-class treatments to address some of the most important unmet patient needs, reported that the U.S. Food and Drug Administration (FDA) has approved CINVANTI (aprepitant) injectable emulsion, for intravenous infusion. CINVANTI is a substance P/neurokinin-1 (NK1) receptor antagonist, indicated in adults, in combination with other antiemetic agents, for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin and nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) (Press release, Heron Therapeutics, NOV 9, 2017, View Source;p=RssLanding&cat=news&id=2316008 [SID1234521870]). With this approval, Heron now is the only company with approved injectable therapies that address the two primary mechanisms of CINV: SUSTOL, a serotonin-3 (5-HT3) receptor antagonist, and CINVANTI, an NK1 receptor antagonist.

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CINVANTI is the first and only polysorbate 80-free, intravenous formulation of an NK1 receptor antagonist indicated for the prevention of acute and delayed CINV. CINVANTI is the first intravenous formulation to directly deliver aprepitant, the active ingredient in EMEND capsules. Aprepitant (including its prodrug, fosaprepitant) is the only single-agent NK1 receptor antagonist to significantly reduce CINV in both the acute phase (0 – 24 hours after chemotherapy) and the delayed phase (24 – 120 hours after chemotherapy).i, ii CINVANTI does not contain polysorbate 80 or any other synthetic surfactant. Pharmaceutical formulations containing polysorbate 80 have been linked to hypersensitivity reactions, including anaphylaxis and irritation of blood vessels resulting in infusion-site pain.ii, iii, iv

CINVANTI was approved based on data demonstrating the bioequivalence of CINVANTI to EMEND IV (fosaprepitant), supporting its efficacy for the prevention of acute and delayed CINV following HEC and MEC.

Results from 2 pivotal randomized, cross-over bioequivalence studies of CINVANTI and EMEND IV showed subjects receiving CINVANTI reported fewer adverse events than those receiving EMEND IV, including substantially fewer infusion-site reactions.v

"CINV remains a high unmet medical need in the oncology community, and 5 full days of CINV coverage continues to be our goal. NK1 receptor antagonists are recommended for routine use with HEC and are a recommended option with MEC. Despite this, NK1 receptor antagonists are underutilized in CINV. This provides a large opportunity for CINVANTI to help more patients avoid CINV and adhere to their chemotherapy regimens," said Jeffrey F. Patton, M.D., Chief Executive Officer of Tennessee Oncology.

"Aprepitant has long been the standard in the NK1 class and it remains the only single-agent NK1 with proven efficacy in preventing CINV in both the acute and delayed phases in HEC and MEC. Because CINVANTI is a novel, polysorbate 80-free IV formulation of aprepitant, it enables physicians to provide patients with standard-of-care efficacy without the potential risk of polysorbate 80-related adverse events, such as infusion-site reactions," said Rudolph M. Navari, M.D., Ph.D., University of Alabama, Birmingham School of Medicine, Director, Cancer Care Program, Division of Hematology Oncology.

"Since both CINVANTI and SUSTOL have been shown to significantly reduce CINV in both the acute and delayed phase, by complementary mechanisms, they are an excellent strategic and operational fit for the Heron commercial team. The commercial team is ready to launch CINVANTI in January of next year," said Barry D. Quart, Pharm.D., Chief Executive Officer of Heron. "To obtain FDA approval for a second product in just over a year is a significant achievement for Heron, and we remain on-track with our third important product, HTX-011, which we expect to file for FDA review in 2018."

Conference Call and Webcast

Heron will host a conference call and webcast on November 9, 2017 at 4:30 PM EST. The conference call can be accessed by dialing 877-311-5906 for domestic callers and 281-241-6150 for international callers. Please provide the operator with the passcode 3496939 to join the conference call. A slide presentation accompanying today’s press release and conference call may also be found on Heron’s website at www.herontx.com under the investor relations section. The conference call will also be available via webcast under the investor relations section of Heron’s website. Please connect to Heron’s website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary. An archive of today’s teleconference and webcast will be available on Heron’s website for 60 days following the call.

About CINVANTI (aprepitant) injectable emulsion

CINVANTI is an intravenous formulation of aprepitant, an NK1 receptor antagonist for the prevention of CINV. CINVANTI is used in combination with a 5-HT3 receptor antagonist and dexamethasone. Heron developed CINVANTI, a proprietary novel lipid emulsion formulation of aprepitant, to overcome the low water solubility of aprepitant without polysorbate 80 or other synthetic surfactants, with the goal to reduce the risk for infusion-site reactions and hypersensitivity reactions that are reported with EMEND IV.

Please see Full Prescribing Information at www.CINVANTI.com.

Important Safety Information for CINVANTI

CINVANTI is contraindicated in patients with hypersensitivity to any of the components of CINVANTI. Serious hypersensitivity reactions, including anaphylaxis and anaphylactic shock, have been reported with fosaprepitant, a prodrug of aprepitant, and with oral aprepitant. Symptoms including flushing, erythema, dyspnea, hypotension and syncope have been reported. If symptoms occur, discontinue CINVANTI. Do not reinstate if symptoms occur with first-time use.

Use of pimozide with CINVANTI is contraindicated due to the risk of significantly increased plasma concentrations of pimozide, potentially resulting in prolongation of the QT interval, a known adverse reaction of pimozide.

Use of CINVANTI may result in clinically significant CYP3A4 Drug Interactions. Aprepitant is a substrate, weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4. Use with other drugs that are CYP3A4 substrates may result in increased plasma concentration of the concomitant drug. Use of CINVANTI with strong or moderate CYP3A4 inhibitors (e.g., ketoconazole, diltiazem) may increase plasma concentrations of aprepitant and result in an increased risk of adverse reactions related to CINVANTI. Use of CINVANTI with strong CYP3A4 inducers (e.g., rifampin) may result in a reduction in aprepitant plasma concentrations and decreased efficacy of aprepitant.

Co-administration of CINVANTI with warfarin, a CYP2C9 substrate, may result in a clinically significant decrease in the International Normalized Ratio (INR) of prothrombin time. Monitor the INR in patients on chronic warfarin therapy in the 2-week period, particularly at 7 to 10 days, following initiation of CINVANTI with each chemotherapy cycle.

The efficacy of hormonal contraceptives may be reduced during administration of and for 28 days following the last dose of CINVANTI. Advise patients to use effective alternative or back-up methods of non-hormonal contraception during treatment with CINVANTI and for 1 month following administration of CINVANTI or oral aprepitant, whichever is administered last.

Avoid use of CINVANTI in pregnant women as alcohol is an inactive ingredient for CINVANTI. There is no safe level of alcohol exposure in pregnancy.

No dosage adjustment is necessary for patients with mild to moderate hepatic impairment (Child-Pugh score 5 to 9). There are no clinical or pharmacokinetic data in patients with severe hepatic impairment (Child-Pugh score greater than 9). Additional monitoring for adverse reactions in these patients may be warranted when CINVANTI is administered.

In general, use caution when dosing elderly patients as they have a greater frequency of decreased hepatic, renal or cardiac function and concomitant disease or other drug therapy.

The most common adverse reactions with the 3-day oral aprepitant regimen in conjunction with MEC (≥1% and greater than standard therapy) were fatigue and eructation.

The most common adverse reactions with the single-dose intravenous fosaprepitant regimen in conjunction with HEC were generally similar to that seen in prior HEC studies with oral aprepitant. In addition, infusion site reactions (3%) occurred.

The most common adverse reactions with a single-dose of CINVANTI (≥2%) were headache and fatigue.

Please see Full Prescribing Information at www.CINVANTI.com.

About SUSTOL (granisetron) extended-release injection

SUSTOL is indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens. SUSTOL is an extended-release, injectable 5-HT3 receptor antagonist that utilizes Heron’s Biochronomer polymer-based drug delivery technology to maintain therapeutic levels of granisetron for ≥5 days. The SUSTOL global Phase 3 development program was comprised of two, large, guideline-based clinical studies that evaluated SUSTOL’s efficacy and safety in more than 2,000 patients with cancer. SUSTOL’s efficacy in preventing nausea and vomiting was evaluated in both the acute phase (0 – 24 hours after chemotherapy) and delayed phase (24 – 120 hours after chemotherapy).

Please see Full Prescribing Information at www.SUSTOL.com.

About Chemotherapy-Induced Nausea and Vomiting (CINV)

While chemotherapy is one of the most effective and commonly used therapies to help patients fight cancer, it is accompanied by debilitating side effects, including varying degrees of nausea and vomiting, often attributed as a leading cause of premature discontinuation of cancer treatment. The goal of antiemetic therapy is to prevent CINV in both the acute phase (0 – 24 hours after chemotherapy) and delayed phase (24 – 120 hours after chemotherapy). The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) have categorized chemotherapy regimens based on the degree to which they cause nausea and vomiting: low emetogenic chemotherapy (LEC); moderately emetogenic chemotherapy (MEC); and highly emetogenic chemotherapy (HEC).

About HTX-011 for Postoperative Pain

HTX-011, which utilizes Heron’s proprietary Biochronomer drug delivery technology, is an investigational, long-acting, extended-release formulation of the local anesthetic bupivacaine in a fixed-dose combination with the anti-inflammatory meloxicam for the prevention of postoperative pain. By delivering sustained levels of both a potent anesthetic and a local anti-inflammatory agent directly to the site of tissue injury, HTX-011 was designed to deliver superior pain relief while reducing the need for systemically administered pain medications such as opioids, which carry the risk of harmful side effects, abuse and addiction. The Phase 2 development program for HTX-011 was designed to target the many patients undergoing a wide range of surgeries who experience significant postoperative pain. Heron has recently initiated the HTX-011 Phase 3 program and expects to file an NDA in 2018.

On November 9, 2017 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, released updated data from the ongoing pilot study of NY‑ESO SPEAR T-cells in synovial sarcoma, as well as an overview of study design for the ongoing NY-ESO SPEAR T-cell trial in myxoid/ round cell liposarcoma (MRCLS) at the annual CTOS meeting at the Grand Wailea Resort in Hawaii (Press release, Adaptimmune, NOV 9, 2017, View Source;p=RssLanding&cat=news&id=2315812 [SID1234521851]).

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"The data from our ongoing pilot study in synovial sarcoma remain encouraging," said Rafael Amado, Adaptimmune’s Chief Medical Officer. "GSK exercised its option over our NY-ESO program and, as a result, these studies, including the pivotal registration trial in synovial sarcoma, will transition to GSK. The synovial sarcoma data, as well as results from other ongoing studies in the NY-ESO program, continue to inform development plans with our wholly owned pipeline of products. We believe the efficacy we have seen in synovial sarcoma is indicative of the potential of our SPEAR T-cell platform."

Data update from the ongoing pilot study of NY-ESO SPEAR T-cells in synovial sarcoma1
During an oral presentation, Dr. Sandra P. D’Angelo of the Memorial Sloan Kettering Cancer Center presented an update on all cohorts from Adaptimmune’s ongoing pilot study of NY-ESO SPEAR T-cells in synovial sarcoma. The data cut-off for this oral presentation was September 5, 2017 and results are summarized below.

NY-ESO SPEAR T-cells continue to be generally well-tolerated with initial efficacy observed in all cohorts including low expressors of NY‑ESO (Cohort 2)
Of the twelve patients treated in Cohort 1 (non-modified fludarabine (Flu) / cyclophosphamide (Cy) lymphodepletion regimen), five remain alive with a median predicted overall survival of 120 weeks (~28 months)
Confirmed responses have been observed across all cohorts as follows:
Cohort 1 (follow-up only; High Flu/Cy, High NY-ESO): 6 /12 (50%) patients (unchanged from ASCO (Free ASCO Whitepaper) 2017)2
Cohort 2 (ongoing; High Flu/Cy, Low NY-ESO): 3/10 (33%) patients (ASCO 2017: 2/5 [40%])
Cohort 3 (follow-up only): 1/5 (20%) patients (unchanged from ASCO (Free ASCO Whitepaper) 2017)
Cohort 4 (ongoing): 4/11 (36%) patients (ASCO 2017: 3/6 [50%]). Overall survival is not mature in this cohort; progression free survival is 23 weeks.
Peak and long-term expansion of NY-ESO SPEAR T-cells appears to correlate with clinical efficacy
All reported events of cytokine release syndrome resolved with supportive care, the majority of events were Grade 1 or 2, and there were no events of seizure, cerebral edema or encephalopathy
1 Oral presentation entitled: "Open label, non-randomized, multi-cohort pilot study of genetically engineered NY-ESO-1 SPEAR T-cells in HLA-A2+ patients with synovial sarcoma (NCT01343043)"

2 Data cut-off for ASCO (Free ASCO Whitepaper) 2017 was March 30, 2017

Overview of Study Design from the Trial in Progress Poster for NY-ESO SPEAR T-cells in MRCLS

Open-label, non-randomized pilot study evaluating the safety, tolerability, and antitumor activity of NY-ESO SPEAR T-cells in patients with MRCLS
Initially, 10 patients are planned to be enrolled, with potential to enroll an additional 5 patients
Patients who do not receive minimum cell dose or who do not receive T‑cell infusion may be replaced
Patients must be: ≥ 18 years old; HLA-A*02:01, *02:05, or *02:06 positive; have advanced (metastatic or inoperable) MRCLS expressing NY-ESO-1 at 2+/3+ intensity in ≥30% of tumor cells by IHC; measurable disease; prior systemic anthracycline therapy; have ECOG status 0 or 1; and adequate organ function.
Lymphodepletion regimen: Flu (30mg/m2/day) and Cy (600 mg/m2/day) for 3 days
Target dose of 1 – 8 × 109 transduced SPEAR T-cells
Efficacy assessed by overall response rate, time to response, duration of response, progression-free survival, and overall survival at weeks 4, 8, and 12, month 6, and then every 3 months until confirmation of disease progression
The study is open and enrolling
Ten patients have already been identified and enrolled

On November 9, 2017 Shire plc (LSE: SHP, NASDAQ: SHPG), the leading biotechnology company focused on serving people with rare diseases, reported the broad range of research it will present at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place December 9-12, 2017, in Atlanta, Georgia (Press release, Shire, NOV 9, 2017, View Source [SID1234521927]). Shire’s presence at ASH (Free ASH Whitepaper) spans its hematology and oncology franchises with 2 oral presentations and 7 poster presentations.

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"Shire’s commitment to fighting rare disease, particularly in hematology and oncology, is reflected in the company’s strong presence at ASH (Free ASH Whitepaper), one of the world’s premier medical conferences focused on blood disorders," said Howard B. Mayer, M.D., SVP and ad-interim Head, Global Research and Development, Shire. "We are committed to continuous and ambitious innovation that helps advance the standards of care and improves outcomes in these therapeutic categories where there remains significant unmet patient need."

HEMATOLOGY
The research presented at ASH (Free ASH Whitepaper) will showcase Shire’s broad hematology portfolio, which covers a wide range of rare bleeding indications and highlights real-world safety and efficacy data. In addition to presenting new research, Shire will share updates related to its ongoing innovation and promising pipeline of investigational treatments. Shire has provided a grant to support a satellite symposium at ASH (Free ASH Whitepaper) hosted by CMEology that is focused on the latest strategies and innovations to help advance best practices in the management of hemophilia:

Advancing Standards in the Management of Hemophilia A: Contemporary Strategies and Innovations. Friday, December 8, 2017, 6:00-10:00 p.m. EST. Hyatt Regency Atlanta, International Ballroom North. For more details or to register, visit: View Source
ONCOLOGY
Shire’s expertise in rare and difficult-to-treat cancers includes ongoing research into investigational pegylated asparaginase, as a component of antineoplastic combination therapy in acute lymphoblastic leukemia (ALL). The company’s pipeline in oncology includes assets being developed for the treatment of metastatic pancreatic cancer, ALL, lung cancer, as well as early stage checkpoint inhibitor and allogeneic CAR T targets. At ASH (Free ASH Whitepaper) 2017, Shire is co-supporting an Independent Medical Education program organized by prIME-Oncology on:

Optimizing Management of Acute Lymphoblastic Leukemia: From Adolescence to Adults. Friday, December 8, 2017, 12:30-4:30 p.m. EST. Hyatt Regency Atlanta, International Ballroom North. For more details or to register, visit: View Source
For further information please contact:
Investor Relations
Ian Karp [email protected] +1 781 482 9018
Robert Coates [email protected] +44 203 549 0874
Media
Gwen Fisher [email protected] +1 781 482 9649
Molly Poarch [email protected] +1 312 965 3413