On May 18, 2016 ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) reported that clinical data on brigatinib, its investigational anaplastic lymphoma kinase (ALK) inhibitor, and Iclusig (ponatinib) will be presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) being held in Chicago, June 3 to 7, 2016 (Press release, Ariad, MAY 18, 2016, View Source;p=irol-newsArticle&ID=2169511 [SID:1234512549]).

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"The first early results are now available from the pivotal Phase 2 ALTA trial of brigatinib in patients with ALK+ non-small cell lung cancer whose disease had progressed on crizotinib therapy, and show encouraging early response rates and progression-free survival. We look forward to the oral presentation at ASCO (Free ASCO Whitepaper), which will reflect approximately three months of additional follow-up, including the opportunity for all responses to be confirmed," stated Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer at ARIAD. "The presentation at ASCO (Free ASCO Whitepaper) will also include details on CNS activity."

The ALTA trial

The primary endpoint of the ALTA (ALK in Lung Cancer Trial of AP26113) trial is investigator-assessed confirmed objective response rate (ORR) as measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Key secondary endpoints include progression free survival (PFS), confirmed ORR assessed by an independent review committee (IRC), CNS response and PFS, duration of response, safety and tolerability. Brigatinib received both Breakthrough Therapy and Orphan Drug designations from the U.S. Food and Drug Administration for the treatment of patients with ALK+ non-small cell lung cancer (NSCLC) whose tumors are resistant to crizotinib.

The trial enrolled 222 patients with ALK+ NSCLC who had been treated with and experienced disease progression on their most recent crizotinib therapy. Patients were randomized one-to-one to receive either 90 mg of brigatinib once per day (QD) (Arm A), or 180 mg QD, preceded by a lead-in dose of 90 mg QD for seven days (Arm B).

In addition, patients were stratified by presence of brain metastases at baseline and best response to prior crizotinib.

Abstract Highlights on ALTA Trial

Data as of December 7, 2015

A total of 222 patients with ALK+ NSCLC treated with prior crizotinib therapy were randomized in the study (110 patients in Arm B at the 180 mg dose level with 7-day lead-in at 90 mg and 112 patients in Arm A at the 90 mg dose level). The last patient enrolled in the study in September 2015.
The median time on treatment was 23 weeks in Arm B and 25 weeks in Arm A.
Investigator-assessed ORR in Arm B was 54% (49 confirmed responses plus 10 single responses awaiting confirmation), including 5 confirmed complete responses. ORR in Arm A was 46% (39 confirmed responses plus 12 single responses awaiting confirmation), including one confirmed complete response.
In the earlier Phase 1/2 trial, of ALK+ NSCLC patients treated with prior crizotinib, 10 responded at the 90 mg dose level and 19 responded at the 180 mg dose level (with a 90 mg lead-in). Of these initial responses, 7 of 10 (70%) and 18 of 19 (95%) respectively were confirmed.
Median PFS was 11.1 months and 8.8 months in Arm B and Arm A, respectively.
The most common treatment-emergent AEs, grade 3 or higher, (Arm B/A) were: increased creatine phosphokinase (CPK) (8%/3%), hypertension (5%/4%), pneumonia (5%/3%), rash (4%/1%), increased lipase (2%/3%) and pneumonitis (3%/2%).
A subset of pulmonary adverse events with early onset occurred in 6% of all patients (in 3% of patients, events were grade 3 or higher); no such events occurred after dose escalation to 180 mg QD in Arm B.
Discontinuations and dose reductions due to AEs (Arm B/A) were 6%/3% and 18%/7%, respectively.
In Arm B 67% of patients had brain metastases and in Arm A 71% of patients had brain metastases. CNS efficacy data will be included in the full ASCO (Free ASCO Whitepaper) presentation.
The schedule and meeting location for the sessions at ASCO (Free ASCO Whitepaper), together with the abstract information and ARIAD’s investor event, are listed below:

Brigatinib Oral Presentation

Title:
Brigatinib (BRG) in patients (pts) with crizotinib (CRZ)- refractory ALK+ non–small cell lung cancer (NSCLC): first report of efficacy and safety from a pivotal randomized phase (ph) 2 trial (ALTA)
Abstract No: 9007
Presenter: Dong-Wan Kim, M.D., Ph.D., (Seoul National University Hospital)
Oral Session: Lung Cancer – Non-Small Cell Metastatic
Session Date & Time: Monday, June 6, 2016, 9:45 a.m. to 12:45 p.m. (CT)
Presentation Time: 11:57 a.m. to 12:09 p.m.
Location: Arie Crown Theater

Brigatinib Posters

Title:
Activity of brigatinib (BRG) in crizotinib (CRZ) resistant patients (pts) according to ALK mutation status
Abstract No: 9060
Presenter: Scott Gettinger, M.D., (Yale Cancer Center)
Poster Session: Lung Cancer – Non-Small Cell Metastatic
Date & Time: Saturday, June 4, 2016, 8:00 a.m. to 11:30 a.m. (CT)
Location: Hall A; poster #383

Title:
Activity and safety of brigatinib (BRG) in patients (pts) with ALK+ non–small cell lung cancer (NSCLC): Phase (ph) 1/2 trial results.
Abstract No: 9057
Presenter: Corey J. Langer, M.D., (University of Pennsylvania Abramson Cancer Center)
Poster Session: Lung Cancer – Non-Small Cell Metastatic
Date & Time: Saturday, June 4, 2016, 8:00 a.m. to 11:30 a.m. (CT)
Location: Hall A; poster #380

Ponatinib Posters

Title:
4-year results of the ponatinib phase 2 PACE trial in patients (pts) with heavily pretreated leukemia
Abstract No: 7013
Presenter: Jorge E. Cortes, M.D., (The University of Texas MD Anderson Cancer Center)
Poster Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
Date & Time: Monday, June 6, 2016, 11:30 a.m. to 12:30 p.m. (CT)
Location: Hall A; poster #5
Discussion: Monday, June 6, 2016, 11:30 a.m. – 12:45 p.m. in room E354b

Title:
Impact of landmark responses on 3 year (yr) outcomes with ponatinib in heavily pretreated CPCML patients (pts)
Abstract No: 7053
Presenter: Martin C. Müller, M.D. (Universitatsmedizin Mannheim, Mannheim)
Poster Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
Date & Time: Monday, June 6, 2016, 11:30 a.m. to 12:30 p.m. (CT)
Location: Hall A; poster #45

Investor and Analyst Briefing and Webcast

A breakfast meeting featuring D. Ross Camidge, M.D., Ph.D., director of thoracic oncology at the University of Colorado to review the updated brigatinib clinical data from the ALTA trial will be webcast live along with slides and can be accessed by visiting the investor relations section of ARIAD’s website at View Source

Date: Monday, June 6, 2016
Time: 7:00 a.m. to 8:00 a.m. (CT)
Location: Hyatt McCormick Place, Prairie Room-B
Space is limited. To request attendance at the meeting, please RSVP to [email protected] by Tuesday, May 31, 2016.

A replay of the investor event will be available on the ARIAD website approximately three hours after the presentation and will be archived on the site for four weeks. To ensure a timely connection to the live webcast, participants should log onto the webcast at least 15 minutes prior to the scheduled start time.

About Iclusig (ponatinib) tablets

Iclusig is approved in the U.S., EU, Switzerland, Canada, Australia and Israel.

Iclusig is a kinase inhibitor indicated in the U.S. for the:

• Treatment of adult patients with T315I-positive chronic myeloid leukemia (chronic phase, accelerated phase, or blast phase) or T315I-positive Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL).

•Treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia or Ph+ ALL for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated.

These indications are based upon response rate. There are no trials verifying an improvement in disease-related symptoms or increased survival with Iclusig.

IMPORTANT SAFETY INFORMATION, INCLUDING THE BOXED WARNING

WARNING: VASCULAR OCCLUSION, HEART FAILURE, and HEPATOTOXICITY

See full prescribing information for complete boxed warning

Vascular Occlusion: Arterial and venous thrombosis and occlusions have occurred in at least 27% of Iclusig treated patients, including fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures. Patients with and without cardiovascular risk factors, including patients less than 50 years old, experienced these events. Monitor for evidence of thromboembolism and vascular occlusion. Interrupt or stop Iclusig immediately for vascular occlusion. A benefit risk consideration should guide a decision to restart Iclusig therapy.
Heart Failure, including fatalities, occurred in 8% of Iclusig-treated patients. Monitor cardiac function. Interrupt or stop Iclusig for new or worsening heart failure.
Hepatotoxicity, liver failure and death have occurred in Iclusig-treated patients. Monitor hepatic function. Interrupt Iclusig if hepatotoxicity is suspected.
Vascular Occlusion: Arterial and venous thrombosis and occlusions, including fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures have occurred in at least 27% of Iclusig-treated patients from the phase 1 and phase 2 trials. Iclusig can also cause recurrent or multi-site vascular occlusion. Overall, 20% of Iclusig-treated patients experienced an arterial occlusion and thrombosis event of any grade. Fatal and life-threatening vascular occlusion has occurred within 2 weeks of starting Iclusig treatment and in patients treated with average daily dose intensities as low as 15 mg per day. The median time to onset of the first vascular occlusion event was 5 months. Patients with and without cardiovascular risk factors have experienced vascular occlusion although these events were more frequent with increasing age and in patients with prior history of ischemia, hypertension, diabetes, or hyperlipidemia. Interrupt or stop Iclusig immediately in patients who develop vascular occlusion events.

Heart Failure: Fatal and serious heart failure or left ventricular dysfunction occurred in 5% of Iclusig-treated patients (22/449). Eight percent of patients (35/449) experienced any grade of heart failure or left ventricular dysfunction. Monitor patients for signs or symptoms consistent with heart failure and treat as clinically indicated, including interruption of Iclusig. Consider discontinuation of Iclusig in patients who develop serious heart failure.

Hepatotoxicity: Iclusig can cause hepatotoxicity, including liver failure and death. Fulminant hepatic failure leading to death occurred in an Iclusig-treated patient within one week of starting Iclusig. Two additional fatal cases of acute liver failure also occurred. The fatal cases occurred in patients with blast phase CML (BP-CML) or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Severe hepatotoxicity occurred in all disease cohorts. Iclusig treatment may result in elevation in ALT, AST, or both. Monitor liver function tests at baseline, then at least monthly or as clinically indicated. Interrupt, reduce or discontinue Iclusig as clinically indicated.

Hypertension: Treatment-emergent hypertension (defined as systolic BP≥140 mm Hg or diastolic BP≥90 mm Hg on at least one occasion) occurred in 67% of patients (300/449). Eight patients treated with Iclusig (2%) experienced treatment-emergent symptomatic hypertension as a serious adverse reaction, including one patient (<1%) with hypertensive crisis. Patients may require urgent clinical intervention for hypertension associated with confusion, headache, chest pain, or shortness of breath. In 131 patients with Stage 1 hypertension at baseline, 61% (80/131) developed Stage 2 hypertension. Monitor and manage blood pressure elevations during Iclusig use and treat hypertension to normalize blood pressure. Interrupt, dose reduce, or stop Iclusig if hypertension is not medically controlled.

Pancreatitis: Clinical pancreatitis occurred in 6% (28/449) of patients (5% Grade 3) treated with Iclusig. Pancreatitis resulted in discontinuation or treatment interruption in 6% of patients (25/449). The incidence of treatment-emergent lipase elevation was 41%. Check serum lipase every 2 weeks for the first 2 months and then monthly thereafter or as clinically indicated. Consider additional serum lipase monitoring in patients with a history of pancreatitis or alcohol abuse. Dose interruption or reduction may be required. In cases where lipase elevations are accompanied by abdominal symptoms, interrupt treatment with Iclusig and evaluate patients for pancreatitis. Do not consider restarting Iclusig until patients have complete resolution of symptoms and lipase levels are less than 1.5 x ULN.

Neuropathy: Peripheral and cranial neuropathy have occurred in Iclusig-treated patients. Overall, 13% (59/449) of Iclusig-treated patients experienced a peripheral neuropathy event of any grade (2%, grade 3/4). In clinical trials, the most common peripheral neuropathies reported were peripheral neuropathy (4%, 18/449), paresthesia (4%, 17/449), hypoesthesia (2%, 11/449), and hyperesthesia (1%, 5/449). Cranial neuropathy developed in 1% (6/449) of Iclusig-treated patients (<1% grade 3/4). Of the patients who developed neuropathy, 31% (20/65) developed neuropathy during the first month of treatment. Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness. Consider interrupting Iclusig and evaluate if neuropathy is suspected.

Ocular Toxicity: Serious ocular toxicities leading to blindness or blurred vision have occurred in Iclusig-treated patients. Retinal toxicities including macular edema, retinal vein occlusion, and retinal hemorrhage occurred in 3% of Iclusig-treated patients. Conjunctival or corneal irritation, dry eye, or eye pain occurred in 13% of patients. Visual blurring occurred in 6% of the patients. Other ocular toxicities include cataracts, glaucoma, iritis, iridocyclitis, and ulcerative keratitis. Conduct comprehensive eye exams at baseline and periodically during treatment.

Hemorrhage: Serious bleeding events, including fatalities, occurred in 5% (22/449) of patients treated with Iclusig. Hemorrhagic events occurred in 24% of patients. The incidence of serious bleeding events was higher in patients with accelerated phase CML (AP-CML), BP-CML, and Ph+ ALL. Most hemorrhagic events, but not all occurred in patients with grade 4 thrombocytopenia. Interrupt Iclusig for serious or severe hemorrhage and evaluate.

Fluid Retention: Serious fluid retention events occurred in 3% (13/449) of patients treated with Iclusig. One instance of brain edema was fatal. In total, fluid retention occurred in 23% of the patients. The most common fluid retention events were peripheral edema (16%), pleural effusion (7%), and pericardial effusion (3%). Monitor patients for fluid retention and manage patients as clinically indicated. Interrupt, reduce, or discontinue Iclusig as clinically indicated.

Cardiac Arrhythmias: Symptomatic bradyarrhythmias that led to a requirement for pacemaker implantation occurred in 1% (3/449) of Iclusig-treated patients. Advise patients to report signs and symptoms suggestive of slow heart rate (fainting, dizziness, or chest pain). Supraventricular tachyarrhythmias occurred in 5% (25/449) of Iclusig-treated patients. Atrial fibrillation was the most common supraventricular tachyarrhythmia and occurred in 20 patients. For 13 patients, the event led to hospitalization. Advise patients to report signs and symptoms of rapid heart rate (palpitations, dizziness). Interrupt Iclusig and evaluate.

Myelosuppression: Severe (grade 3 or 4) myelosuppression occurred in 48% (215/449) of patients treated with Iclusig. The incidence of these events was greater in patients with AP-CML, BP-CML and Ph+ ALL than in patients with CP-CML. Obtain complete blood counts every 2 weeks for the first 3 months and then monthly or as clinically indicated, and adjust the dose as recommended.

Tumor Lysis Syndrome: Two patients (<1%) with advanced disease (AP-CML, BP-CML, or Ph+ ALL) treated with Iclusig developed serious tumor lysis syndrome. Hyperuricemia occurred in 7% (30/449) of patients overall; the majority had CP-CML (19 patients). Due to the potential for tumor lysis syndrome in patients with advanced disease, ensure adequate hydration and treat high uric acid levels prior to initiating therapy with Iclusig.

Compromised Wound Healing and Gastrointestinal Perforation: Since Iclusig may compromise wound healing, interrupt Iclusig for at least 1 week prior to major surgery. Serious gastrointestinal perforation (fistula) occurred in one patient 38 days post-cholecystectomy.

Embryo-Fetal Toxicity: Iclusig can cause fetal harm. If Iclusig is used during pregnancy, or if the patient becomes pregnant while taking Iclusig, the patient should be apprised of the potential hazard to the fetus. Advise women to avoid pregnancy while taking Iclusig.

Most common non-hematologic adverse reactions: (≥20%) were hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation, arthralgia, nausea, and pyrexia. Hematologic adverse reactions included thrombocytopenia, anemia, neutropenia, lymphopenia, and leukopenia.

Please see the full U.S. Prescribing Information for Iclusig, including the Boxed Warning, for additional important safety information.

On May 18, 2016 Puma Biotechnology, Inc. (NYSE: PBYI), a biopharmaceutical company, reported the release of an abstract on its drug candidate PB272 (neratinib) that will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which will be held June 3–7, 2016, in Chicago (Press release, Puma Biotechnology, MAY 18, 2016, View Source [SID:1234512548]). Abstracts are available to the public online on the ASCO (Free ASCO Whitepaper) website: www.abstract.asco.org.

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Abstract #516: Phase II Trial of Neratinib for HER2 Mutated, Non-Amplified Metastatic Breast Cancer (HER2mut MBC)

Poster Session: Breast Cancer-HER2/ER; Sunday, June 5, 8:00–11:30 a.m. CDT, Hall A, Poster Board #4

The abstract will be included in the Poster Discussion Session: Breast Cancer—HER2/ER; Sunday, June 5, 11:30 a.m.–12:45 p.m. CDT, June 5, Hall D2

On May 18, 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 in partnership with its collaborators it will present key clinical updates on its investigational products JCAR014, JCAR015 and JCAR017 at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2016 in Chicago, Illinois from June 3-7 (Press release, Juno, MAY 18, 2016, View Source;p=irol-newsArticle&ID=2169503 [SID:1234512547]).

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JCAR014, JCAR015 and JCAR017 are chimeric antigen receptor (CAR) T cell product candidates that target CD19, a protein expressed on the surface of almost all B cell malignancies, including acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), and chronic lymphocytic leukemia (CLL). New data from the ongoing JCAR014 trial in patients with relapsed or refractory ALL, NHL, or CLL will be presented, with increased patient numbers and longer duration of follow-up compared to previous presentations. Investigators will also present updated data from the ongoing trial of JCAR017 in children with relapsed or refractory ALL, including the first experience of patients treated with the pre-conditioning regimen of fludarabine/cyclophosphamide. Ongoing data from the phase I experience of JCAR015 will also be presented, including in adult patients with relapsed or refractory ALL.

Key data presentations at ASCO (Free ASCO Whitepaper) include:
JCAR014
Rate of Durable Complete Response in ALL, NHL, and CLL After Immunotherapy with Optimized Lymphodepletion and Defined Composition CD19 CAR-T Cells
Oral abstract 102
Presenter: Cameron J. Turtle, MBBS, Ph.D. of the Fred Hutchinson Cancer Research Center
Date: Saturday, June 4, 2016: 8:48 a.m. Central Time
Location: Hall D1

JCAR017
Prolonged Functional Persistence of CD19 CAR T Cell Products of Defined CD4:CD8 Composition and Transgene Expression Determines Durability of MRD-Negative ALL Remission
Presenter: Rebecca Gardner, M.D. of Seattle Children’s Research Institute
Date: Sunday, June 5, 2016: 8:00 – 11:30 a.m. Central Time
Location: Hall A, Poster Board #370

JCAR015
Impact of Disease Burden on Long-Term Outcome of 19-28z CAR Modified T Cells in Adult Patients with Relapsed B-ALL
Presenter: Jae H. Park, M.D. of Memorial Sloan Kettering Cancer Center
Date: Saturday, June 4, 2016: 4:00 p.m. Central Time
Location: Arie Crown Theatre

Updated Results: Phase I Trial of Autologous CD19-Targeted CAR T Cells in Patients with Residual CLL Following Initial Purine Analog-Based Therapy
Presenter: Mark B. Geyer, M.D., Department of Medicine, Memorial Sloan Kettering Cancer Center
Date: Monday, June 6, 2016: 8:00 – 11:30 a.m. Central Time
Location: Hall A, Poster Board #82

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, JCAR015, and JCAR017 are investigational product candidates and their safety and efficacy have not been established.

On May 18, 2016 Novocure (NASDAQ: NVCR) reported that a new subgroup analysis of its ongoing phase 2 pilot PANOVA clinical trial will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago on June 3-7, 2016, demonstrating an overall survival benefit in advanced pancreatic cancer patients treated with Tumor Treating Fields (TTFields) combined with gemcitabine compared to historical controls of gemcitabine alone (Press release, NovoCure, MAY 18, 2016, View Source [SID:1234512546]).

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Results were obtained from the first of two 20-patient cohorts. Of the 20 patients in the first cohort of the trial, 13 had distant metastases and seven had locally advanced unresectable disease. Locally advanced pancreatic cancer is a tumor that has not yet spread to distant organs, yet it cannot be removed entirely by surgery because it has grown into nearby major blood vessels. Roughly 30 percent of pancreatic cancer patients are diagnosed with locally advanced unresectable disease, and roughly 50 percent of pancreatic cancer patients are diagnosed with metastatic disease.

PANOVA patients experienced a median progression free survival (PFS) of 8.3 months (95% Cl 4.3, 10.3), with locally advanced patients reaching a median PFS of 10.3 months (95% Cl 2.8, NA) and patients with metastatic disease reaching a median PFS of 5.7 months (95% CI 3.8 -10.3). PFS rate at six months was 56 percent. Of the 19 out of 20 evaluable tumors, 30 percent had partial response and another 30 percent had stable disease.

The median overall survival (OS) for all patients was 14.9 months. Median OS was longer than 15 months in locally advanced patients with 86% of patients alive at end of follow up. Patients with metastatic disease experienced a median OS of 8.3 months (95% Cl 4.3-14.9). The one-year survival rate was 55 percent – 86 percent in locally advanced and 40 percent in metastatic disease.

"The results of this subgroup analysis are very telling, demonstrating that pancreatic cancer patients who are treated with TTFields therapy plus gemcitabine before their cancer metastasizes could have a greater chance of survival," said Dr. Eilon Kirson, Chief Science Officer and Head of Research and Development at Novocure. "We believe TTFields therapy plus gemcitabine could dramatically improve survival in advanced pancreatic cancer patients."

Novocure presented data from the first cohort of PANOVA at ASCO (Free ASCO Whitepaper) GI in January 2016, suggesting an increase in PFS and OS for patients receiving TTFields in combination with gemcitabine compared to historical controls of gemcitabine alone. Novocure will complete enrollment for the second cohort of PANOVA this year. After obtaining data from the first cohort of PANOVA, Novocure accelerated planning for a phase 3 pivotal trial in pancreatic cancer.

"Pancreatic cancer is one of the most lethal cancers, and it is most often diagnosed at advanced stages, when surgery is not a curative option," said Asaf Danziger, CEO of Novocure. "Our early data in this cancer type suggest TTFields therapy could make a meaningful difference in the lives of patients with this devastating disease." Novocure will also have two e-publications featured at ASCO (Free ASCO Whitepaper)’s Annual Meeting:
The antitumor activity of alternating electric fields (TTFields) in combination with immune checkpoint inhibitors
Development of practice algorithms to guide treatment planning with TTFields for the management of glioblastoma (GBM)
During the conference, Novocure representatives will be at booth #6109.

About Pancreatic Cancer

Pancreatic cancer is the fourth leading cause of cancer death in the U.S. The National Cancer Institute estimated that about 48,960 people would be diagnosed with pancreatic cancer and about 40,560 people would die from the disease in 2015. Five-year survival among pancreatic cancer patients is less than 6 percent. Tumor Treating Fields (TTFields) therapy is not approved for the treatment of pancreatic cancer by the U.S. Food and Drug Administration. The safety and effectiveness of TTFields therapy for pancreatic cancer has not been established.

On May 18, 2016 Pfizer Inc. (NYSE:PFE) reported that the company will have its largest presence to date at the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago from June 3-7, with more than 40 abstracts spanning a diverse and growing portfolio seeking to tackle numerous cancers and mechanisms of action (Press release, Pfizer, MAY 18, 2016, View Source [SID:1234512545]). Presentations include eight oral presentations and five poster discussions that span Pfizer’s internal and collaborative scientific advances. Highlights include the first presentation of a novel immunotherapy combination study involving a 4-1BB agonist and checkpoint inhibitor as a potential new immunotherapy strategy and new clinical data featuring breakthrough treatments IBRANCE (palbociclib) and XALKORI (crizotinib), as well as investigational assets avelumab, an anti-PD-L1 IgG1 monoclonal antibody that is being developed in collaboration with Merck KGaA, Darmstadt, Germany, and lorlatinib, a next-generation ALK/ROS1 tyrosine kinase inhibitor.

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"Our significant presence at ASCO (Free ASCO Whitepaper) underscores our long-term commitment to oncology, cutting-edge science and the strength of collaborations to help bring forward potential new medicines that address the serious and complex needs of people battling cancer," said Liz Barrett, global president and general manager, Pfizer Oncology. "We look forward to sharing our findings with the entire oncology community with the hope that our collective efforts will continue to advance innovative approaches and redefine life with cancer."

Immuno-Oncology Highlights

New clinical data from Pfizer’s growing immuno-oncology portfolio features an oral presentation on utomilumab (the proposed generic name for PF-05082566), Pfizer’s novel 4-1BB agonist, in combination with pembrolizumab, a PD-1 inhibitor, in patients with a variety of advanced solid tumors. Numerous other presentations offer new insights from the JAVELIN clinical development program of avelumab, the proposed nonproprietary name for the anti-PD-L1 mAb (also known as MSB0010718C), including new data from the registrational, Phase 2 trial in second-line metastatic Merkel cell carcinoma (MCC).

"Immunotherapy is revolutionizing the treatment of cancer, and Pfizer is advancing a diverse immuno-oncology pipeline with promise for patients with numerous types of cancer," said Chris Boshoff, vice president and head of early development, translational and immuno-oncology for Pfizer Oncology.

Key oral immuno-oncology presentations include:

Phase 1b study of PF-05082566 in combination with pembrolizumab in patients with advanced solid tumors (Tolcher et al)
Avelumab (MSB0010718C; anti-PD-L1) in patients with metastatic Merkel cell carcinoma previously treated with chemotherapy: Results of the Phase 2 JAVELIN Merkel 200 trial (Kaufman et al)
Avelumab (MSB0010718C; anti-PD-L1) in patients with advanced unresectable mesothelioma from the JAVELIN solid tumor phase 1b trial: Safety, clinical activity, and PD-L1 expression (Hassan et al)
Breast Cancer Highlights

IBRANCE data to be presented at ASCO (Free ASCO Whitepaper) demonstrate Pfizer’s continued leadership in breast cancer and add to the growing body of knowledge around this first-in-class CDK 4/6 inhibitor in metastatic breast cancer. Since its FDA approval in February 2015, more than 28,000 women have been prescribed IBRANCE by more than 6,800 prescribers in the U.S. IBRANCE is the only CDK 4/6 inhibitor with Phase 3 data in this disease. New Phase 3 PALOMA-2 data to be presented at ASCO (Free ASCO Whitepaper) represent the third randomized pivotal study of IBRANCE in combination with endocrine therapy to demonstrate clinical benefit for women with HR+, HER2- metastatic breast cancer.

Key abstracts include:

PALOMA-2: Primary results from a phase III trial of palbociclib with letrozole compared with letrozole alone in postmenopausal women with ER+/HER2- advanced breast cancer (Finn et al)
Efficacy of palbociclib plus fulvestrant in patients with metastatic breast cancer and ESR1 mutations in circulating tumor DNA (Turner at al)
Lung Cancer Highlights

Pfizer’s continuing leadership in biomarker-driven treatments for lung cancer will be represented by new data on XALKORI and next-generation investigational treatment lorlatinib, the proposed generic name for PF-06463922.

Key abstracts include:

Safety and efficacy of lorlatinib (PF-06463922) from the dose-escalation component of a study in patients with advanced ALK+ or ROS1+ non-small cell lung cancer (Solomon et al)
Phase II study of crizotinib in East Asian patients with ROS1-positive advanced non-small cell lung cancer (Goto et al)
Efficacy and safety of crizotinib in patients with advanced MET Exon 14-altered non-small cell lung cancer (Drilon et al)
Pfizer Oral Presentation Planner

Title/Abstract Number Date/Time (CDT) Location
(Abstract 512) Efficacy of palbociclib plus fulvestrant (P+F) in patients with metastatic breast cancer and ESR1 mutations in circulating tumor DNA
Turner N

Friday, June 3
5:18 – 5:30 p.m.

Hall D1
(Abstract 3002) Phase 1b study of PF-05082566 in combination with pembrolizumab in patients with advanced solid tumors
Tolcher A

Saturday, June 4
1:39 – 1:51 p.m.

Hall B1
(Abstract 8503) Avelumab* (MSB0010718C; anti-PD-L1) in patients with advanced unresectable mesothelioma from the JAVELIN solid tumor phase 1b trial: Safety, clinical activity, and PD-L1 expression

Hassan R

Sunday, June 5
8:58 – 9:10 a.m.

Arie Crown Theater
(Abstract 11509) Crizotinib in children and adolescents with advanced ROS1, MET, or ALK-rearranged cancer: Results of the AcSé phase II trial
Vassal G

Monday, June 6
9:45 – 9:57 a.m.

S404
(Abstract 108) Efficacy and safety of crizotinib in patients with advanced MET Exon 14-altered non-small cell lung cancer
Drilon A

Monday, June 6
10:09 – 10:21 a.m.

Hall D1
(Abstract 9009) Safety and efficacy of lorlatinib (PF-06463922) from the dose-escalation component of a study in patients with advanced ALK+ or ROS1+ non-small cell lung cancer
Solomon B

Monday, June 6
1:15 – 1:27 p.m.

Hall D2
(Abstract 507)
PALOMA-2: Primary results from a phase III trial of palbociclib with letrozole compared with letrozole alone in postmenopausal women with ER+/HER2- advanced breast cancer

Slamon D

Monday, June 6
3:27 – 3:39 pm

Hall D1
(Abstract 9508)
Avelumab* (MSB0010718C; anti-PD-L1) in patients with metastatic Merkel cell carcinoma previously treated with chemotherapy: Results of the phase 2 JAVELIN Merkel 200 trial

Kaufman H

Monday, June 6
3:39 – 3:51 p.m.

Arie Crown Theater
* Avelumab is being developed through an alliance between Merck KGaA, Darmstadt, Germany, and Pfizer

For a complete list of Pfizer-sponsored abstracts featuring data on our broad pipeline of biologics and small molecules, please visit: View Source

Learn more about how Pfizer Oncology is applying innovative approaches to improve the outlook for people living with cancer at View Source

Post-ASCO Analyst Conference Call

Pfizer invites investors and the general public to view and listen to a webcast of a conference call with investment analysts on Wednesday, June 8, 2016 at 10 a.m. EDT to review Pfizer’s oncology business and ASCO (Free ASCO Whitepaper) data presentations.

To pre-register for and access the webcast and conference call, please visit the For Investors section of www.pfizer.com. You can also listen to the conference call by dialing (855) 895-8759 in the United States and Canada or (503) 343-6044 in other countries. The password is ASCO (Free ASCO Whitepaper). The webcast will be archived on www.pfizer.com.

About IBRANCE (palbociclib) 125mg capsules

IBRANCE is an oral inhibitor of CDKs 4 and 6,i which are key regulators of the cell cycle that trigger cellular progression.ii,iii IBRANCE is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer in combination with letrozole as initial endocrine based therapy in postmenopausal women, or fulvestrant in women with disease progression following endocrine therapy.i The indication in combination with letrozole is approved under accelerated approval based on progression-free survival (PFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.i

IBRANCE Important Safety Information

Neutropenia was the most frequently reported adverse reaction in Study 1 (PALOMA-1) (75%) and Study 2 (PALOMA-3) (83%). In Study 1, Grade 3 (57%) or 4 (5%) decreased neutrophil counts were reported in patients receiving IBRANCE plus letrozole. In Study 2, Grade 3 (56%) or Grade 4 (11%) decreased neutrophil counts were reported in patients receiving IBRANCE plus fulvestrant. Febrile neutropenia has been reported in about 1% of patients exposed to IBRANCE. One death due to neutropenic sepsis was observed in Study 2. Inform patients to promptly report any fever.

Monitor complete blood count prior to starting IBRANCE, at the beginning of each cycle, on Day 14 of first 2 cycles, and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.

Pulmonary embolism (PE) has been reported at a higher rate in patients treated with IBRANCE plus letrozole in Study 1 (5%) and in patients treated with IBRANCE plus fulvestrant in Study 2 (1%) compared with no cases in patients treated either with letrozole alone or fulvestrant plus placebo. Monitor for signs and symptoms of PE and treat as medically appropriate.

Based on the mechanism of action, IBRANCE can cause fetal harm. Advise females of reproductive potential to use effective contraception during IBRANCE treatment and for at least 3 weeks after the last dose. IBRANCE may impair fertility in males and has the potential to cause genotoxicity. Advise male patients with female partners of reproductive potential to use effective contraception during IBRANCE treatment and for 3 months after the last dose. Advise females to inform their healthcare provider of a known or suspected pregnancy. Advise women not to breastfeed during IBRANCE treatment and for 3 weeks after the last dose because of the potential for serious adverse reactions in nursing infants.

The most common adverse reactions (≥10%) of any grade reported in Study 1 of IBRANCE plus letrozole vs letrozole alone included neutropenia (75% vs 5%), leukopenia (43% vs 3%), fatigue (41% vs 23%), anemia (35% vs 7%), upper respiratory infection (31% vs 18%), nausea (25% vs 13%), stomatitis (25% vs 7%), alopecia (22% vs 3%), diarrhea (21% vs 10%), thrombocytopenia (17% vs 1%), decreased appetite (16% vs 7%), vomiting (15% vs 4%), asthenia (13% vs 4%), peripheral neuropathy (13% vs 5%), and epistaxis (11% vs 1%).

Grade 3/4 adverse reactions (≥10%) in Study 1 reported at a higher incidence in the IBRANCE plus letrozole group vs the letrozole alone group included neutropenia (54% vs 1%) and leukopenia (19% vs 0%). The most frequently reported serious adverse events in patients receiving IBRANCE plus letrozole were pulmonary embolism (4%) and diarrhea (2%).

Lab abnormalities occurring in Study 1 (all grades, IBRANCE plus letrozole vs letrozole alone) were decreased WBC (95% vs 26%), decreased neutrophils (94% vs 17%), decreased lymphocytes (81% vs 35%), decreased hemoglobin (83% vs 40%), and decreased platelets (61% vs 16%).

The most common adverse reactions (≥10%) of any grade reported in Study 2 of IBRANCE plus fulvestrant vs fulvestrant plus placebo included neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%), stomatitis (28% vs 13%), headache (26% vs 20%), diarrhea (24% vs 19%), thrombocytopenia (23% vs 0%), constipation (20% vs 16%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16% vs 8%), and pyrexia (13% vs 5%).

Grade 3/4 adverse reactions (≥10%) in Study 2 reported at a higher incidence in the IBRANCE plus fulvestrant group vs the fulvestrant plus placebo group included neutropenia (66% vs 1%) and leukopenia (31% vs 2%). The most frequently reported serious adverse reactions in patients receiving IBRANCE plus fulvestrant were infections (3%), pyrexia (1%), neutropenia (1%), and pulmonary embolism (1%).

Lab abnormalities occurring in Study 2 (all grades, IBRANCE plus fulvestrant vs fulvestrant plus placebo) were decreased WBC (99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%), and decreased platelets (62% vs 10%).

Avoid concurrent use of strong CYP3A inhibitors. If patients must be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg/day. If the strong inhibitor is discontinued, increase the IBRANCE dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit juice may increase plasma concentrations of IBRANCE and should be avoided. Avoid concomitant use of strong CYP3A inducers. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced as IBRANCE may increase their exposure.

IBRANCE has not been studied in patients with moderate to severe hepatic impairment or in patients with severe renal impairment (CrCl <30 mL/min).

The full prescribing information for IBRANCE can be found at www.pfizer.com.

About XALKORI (crizotinib)

XALKORI is a kinase inhibitor indicated in the U.S. for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test, and for the treatment of patients with metastatic NSCLC whose tumors are ROS1-positive. XALKORI was the first ALK inhibitor approved in the U.S. and has been used to treat more than 8,000 patients to date.iv

XALKORI Important Safety Information

Hepatotoxicity: Drug-induced hepatotoxicity with fatal outcome occurred in 0.1% of patients treated with XALKORI across clinical trials (n=1719). Transaminase elevations generally occurred within the first 2 months. Monitor with liver function tests including ALT, AST, and total bilirubin every 2 weeks during the first 2 months of treatment, then once a month and as clinically indicated, with more frequent repeat testing for increased liver transaminases, alkaline phosphatase, or total bilirubin in patients who develop transaminase elevations. Permanently discontinue for ALT/AST elevation >3 times ULN with concurrent total bilirubin elevation >1.5 times ULN (in the absence of cholestasis or hemolysis); otherwise, temporarily suspend and dose-reduce XALKORI as indicated.

Interstitial Lung Disease (Pneumonitis): Severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis can occur. Across clinical trials (n=1719), 2.9% of XALKORI-treated patients had any grade ILD, 1.0% had Grade 3/4, and 0.5% had fatal ILD. ILD generally occurred within 3 months after initiation of treatment. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Exclude other potential causes and permanently discontinue XALKORI in patients with drug-related ILD/pneumonitis.

QT Interval Prolongation: QTc prolongation can occur. Across clinical trials (n=1616), 2.1% of patients had QTcF (corrected QT by the Fridericia method) ≥500 ms and 5.0% had an increase from baseline QTcF ≥60 ms by automated machine-read evaluation of ECGs. Avoid use in patients with congenital long QT syndrome. Monitor with ECGs and electrolytes in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that prolong the QT interval. Permanently discontinue XALKORI in patients who develop QTc >500 ms or ≥60 ms change from baseline with Torsade de pointes, polymorphic ventricular tachycardia, or signs/symptoms of serious arrhythmia. Withhold XALKORI in patients who develop QTc >500 ms on at least 2 separate ECGs until recovery to a QTc ≤480 ms, then resume at a reduced dose.

Bradycardia: Symptomatic bradycardia can occur. Across clinical trials, bradycardia occurred in 12.7% of patients treated with XALKORI (n=1719). Avoid use in combination with other agents known to cause bradycardia. Monitor heart rate and blood pressure regularly. In cases of symptomatic bradycardia that is not life-threatening, hold XALKORI until recovery to asymptomatic bradycardia or to a heart rate of ≥60 bpm, re-evaluate the use of concomitant medications, and adjust the dose of XALKORI. Permanently discontinue for life-threatening bradycardia due to XALKORI; however, if associated with concomitant medications known to cause bradycardia or hypotension, hold XALKORI until recovery to asymptomatic bradycardia or to a heart rate of ≥60 bpm. If concomitant medications can be adjusted or discontinued, restart XALKORI at 250 mg once daily with frequent monitoring.

Severe Visual Loss: Across clinical trials, the incidence of Grade 4 visual field defect with vision loss was 0.2% (n=1719). Discontinue XALKORI in patients with new onset of severe visual loss (best corrected vision less than 20/200 in one or both eyes). Perform an ophthalmological evaluation. There is insufficient information to characterize the risks of resumption of XALKORI in patients with a severe visual loss; a decision to resume should consider the potential benefits to the patient.

Vision Disorders: Most commonly visual impairment, photopsia, blurred vision or vitreous floaters, occurred in 63.1% of 1719 patients. The majority (95%) of these patients had Grade 1 visual adverse reactions. 0.8% of patients had Grade 3 and 0.2% had Grade 4 visual impairment. The majority of patients on the XALKORI arms in Studies 1 and 2 (>50%) reported visual disturbances which occurred at a frequency of 4-7 days each week, lasted up to 1 minute, and had mild or no impact on daily activities.

Embryo-Fetal Toxicity: XALKORI can cause fetal harm when administered to a pregnant woman. Advise of the potential risk to the fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for at least 45 days (females) or 90 days (males) respectively, following the final dose of XALKORI.

ROS1-positive Metastatic NSCLC: Safety was evaluated in 50 patients with ROS1-positive metastatic NSCLC from a single-arm study, and was generally consistent with the safety profile of XALKORI evaluated in patients with ALK-positive metastatic NSCLC. Vision disorders occurred in 92% of patients in the ROS1 study; 90% of patients had Grade 1 vision disorders and 2% had Grade 2.

Adverse Reactions: Safety was evaluated in a phase 3 study in previously untreated patients with ALK-positive metastatic NSCLC randomized to XALKORI (n=171) or chemotherapy (n=169). Serious adverse events were reported in 34% of patients treated with XALKORI, the most frequent were dyspnea (4.1%) and pulmonary embolism (2.9%). Fatal adverse events in XALKORI-treated patients occurred in 2.3% of patients, consisting of septic shock, acute respiratory failure, and diabetic ketoacidosis. Common adverse reactions (all grades) occurring in ≥25% and more commonly (≥5%) in patients treated with XALKORI vs chemotherapy were vision disorder (71% vs 10%), diarrhea (61% vs 13%), edema (49% vs 12%), vomiting (46% vs 36%), constipation (43% vs 30%), upper respiratory infection (32% vs 12%), dysgeusia (26% vs 5%), and abdominal pain (26% vs 12%). Grade 3/4 reactions occurring at a ≥2% higher incidence with XALKORI vs chemotherapy were QT prolongation (2% vs 0%), and constipation (2% vs 0%). In patients treated with XALKORI vs chemotherapy, the following occurred: elevation of ALT (any grade [79% vs 33%] or Grade 3/4 [15% vs 2%]); elevation of AST (any grade [66% vs 28%] or Grade 3/4 [8% vs 1%]); neutropenia (any grade [52% vs 59%] or Grade 3/4 [11% vs 16%]); lymphopenia (any grade [48% vs 53%] or Grade 3/4 [7% vs 13%]); hypophosphatemia (any grade [32% vs 21%] or Grade 3/4 [10% vs 6%]). In patients treated with XALKORI vs chemotherapy, renal cysts occurred (5% vs 1%). Nausea (56%), decreased appetite (30%), fatigue (29%), and neuropathy (21%) also occurred in patients taking XALKORI.

Drug Interactions: Exercise caution with concomitant use of moderate CYP3A inhibitors. Avoid grapefruit or grapefruit juice which may increase plasma concentrations of crizotinib. Avoid concomitant use of strong CYP3A inducers and inhibitors. Avoid concomitant use of CYP3A substrates with narrow therapeutic range in patients taking XALKORI. If concomitant use of CYP3A substrates with narrow therapeutic range is required in patients taking XALKORI, dose reductions of the CYP3A substrates may be required due to adverse reactions.

Lactation: Because of the potential for adverse reactions in breastfed infants, advise females not to breast feed during treatment with XALKORI and for 45 days after the final dose.

Hepatic Impairment: XALKORI has not been studied in patients with hepatic impairment. As crizotinib is extensively metabolized in the liver, hepatic impairment is likely to increase plasma crizotinib concentrations. Use caution in patients with hepatic impairment.

Renal Impairment: Decreases in estimated glomerular filtration rate occurred in patients treated with XALKORI. Administer XALKORI at a starting dose of 250 mg taken orally once daily in patients with severe renal impairment (CLcr <30 mL/min) not requiring dialysis. No starting dose adjustment is needed for patients with mild and moderate renal impairment.

For more information and full Prescribing Information, visit www.XALKORI.com (link is external).