On November 22, 2016 Opsona Therapeutics Ltd (‘Opsona’), the innate immune drug development company focused on novel therapeutic approaches to treat oncology, autoimmune and other inflammatory diseases, reported that it will present preliminary results from its ongoing prospective, open label Phase I/II study being conducted with OPN-305 in second-line lower (Low and intermediate-1) risk myelodysplastic syndrome (MDS) (Press release, Opsona Therapeutics, NOV 22, 2016, View Source [SID1234516770]). The presentation will take place on Saturday, 3 December at the 58th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego.

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Myelodysplastic syndromes are a complex and heterogeneous group of bone marrow failure disorders characterized by ineffective hematopoiesis and poor prognosis. There is an urgent need for the development of novel therapies in the treatment of MDS which can delay progression, improve patient survival and quality of life, and which have fewer adverse effects. Opsona has recently received orphan drug designation (ODD) from the United States Food and Drug Administration for MDS.

OPN-305 is a novel proprietary humanized IgG4 monoclonal antibody (MAb) against Toll-Like Receptor 2 (TLR2), a key target within the innate immune system.

The study in patients with lower risk MDS who have failed hypomethylating agents is ongoing in collaboration with MD Anderson Cancer Center in Houston USA with additional sites now being added in the USA. The lead principal investigator Professor Guillermo Garcia-Manero will present the preliminary data at ASH (Free ASH Whitepaper) and commenting on today’s announcement said "Inhibition of TLR2 with OPN-305 is safe and is currently demonstrating strong clinical activity in patients with lower risk MDS after hypomethylating agent therapy"

Details of the presentation are as follows:

A Clinical Study of OPN-305, a Toll-like receptor 2 (TLR-2) antibody, in patients with Lower Risk Myelodysplastic Syndromes (MDS) that have received prior Hypomethylating Agent (HMA) Therapy

Abstract # 227

Session Name: 637. Myelodysplastic Syndromes—Clinical Studies: Lower Risk MDS Clinical Studies

Session Date: Saturday, December 3, 2016

Session Time: 4:00 PM – 5:30 PM

Presentation Time: 5:00 PM

Room: Manchester Grand Hyatt San Diego, Grand Hall C

The ASH (Free ASH Whitepaper) abstract is now online can be accessed here:

View Source

On November 22, 2016 Cellectis S.A. (Paris:ALCLS) (NASDAQ:CLLS) (Alternext: ALCLS – Nasdaq: CLLS), a biopharmaceutical company focused on developing immunotherapies based on gene edited CAR T-cells (UCART), reported its results for the three-month period ended September 30, 2016 and for the nine-month period ended September 30, 2016 (Filing, Q3, Cellectis, 2016, NOV 22, 2016, View Source [SID1234516771]).

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Recent Corporate Highlights

UCART19 in collaboration with Servier / Pfizer

On June 20, 2016, Cellectis announced that the first patient in Servier’s UCART19 Phase 1 clinical trial had been dosed. The UCART19 Phase 1 clinical trial in ALL and CLL patients is conducted at two clinical sites in the UK – at the Great Ormond Street Hospital (GOSH), part of UCL, for the pediatric arm of the trial, and at Kings College London for the adult arm of the study.
Interim data from the UCART19 Phase 1 clinical trial is expected to be announced at a scientific meeting in H1 2017.
UCART123

On November 15, 2016, Cellectis announced the successful completion of large scale production runs of UCART123, according to cGMP standards. Cellectis is planning to file an IND for a Phase 1 clinical trial in AML and BPDCN patients by YE 2016 in collaboration with the Weill Cornell Medical College and the MD Anderson Cancer Center.
Weill Cornell will present pre-clinical data on UCART123 in an oral presentation at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. The meeting will be held from December 3 to 6, 2016 in San Diego.
Pfizer Partnership

Cellectis and Pfizer are making advances in their partnered programs. Notably, Pfizer will present on the "Preclinical Evaluation of Allogeneic Anti-BCMA Chimeric Antigen Receptor T Cells with Safety Switch Domains and Lymphodepletion Resistance for the Treatment of Multiple Myeloma" in an oral presentation at ASH (Free ASH Whitepaper) in December 2016.
IP / Patent Portfolio

Issuance of U.S. patent 9,458,439 – which claims gene inactivation by use of chimeric restriction endonucleases. This patent, granted by the USPTO to the Institut Pasteur and Boston Children’s Hospital, naming Dr. André Choulika and Pr. Richard C. Mulligan as co-inventors, is exclusively licensed to Cellectis.
Award

Cellectis won EuropaBio’s 2016 Most Innovative European Biotech SME Award for the healthcare category. The Awards program is a unique annual initiative that recognizes innovative biotech small- and medium-sized enterprises (SMEs) in Europe and the crucial role that they play in answering some of society’s greatest challenges through biotechnology.
Conferences

Cellectis will participate in the upcoming Oppenheimer Life Sciences Summit being held in NYC on November 29, 2016 and will be presenting at the Piper Jaffray 28th Annual Health Care Conference on November 30, 2016 in NYC.
Calyxt – Cellectis’ plant science subsidiary

Calyxt expanded its patent portfolio with U.S. patent 9,458,439, which encompasses broad uses of technologies such as CRISPR/Cas9, Zinc Finger Nucleases and TAL-effector Nucleases for plant gene editing.
On October 20, 2016 Cellectis hosted, along with its agricultural biotech subsidiary Calyxt, the world’s first dinner made with gene edited foods in New York.
Calyxt has completed the 2016 expansion of its high-oleic/no trans-fat soybean variety (CAL1501) in the U.S. with a production of 1,200 tons of beans. In Spring 2016, Calyxt planted 942 acres (381 hectares) in six U.S. states – Illinois, Iowa, Michigan, Minnesota, South Dakota and Wisconsin. To date, the Company has harvested approximately 45,000 bushels with the intent to use a substantial portion of the harvest for its first industrial scale crush.
Financial Results

Cellectis’ consolidated financial statements have been prepared in accordance with International Financial Reporting Standards, or IFRS, as issued by the International Accounting Standards Board ("GAAP").

Third Quarter 2016 Financial Results

Cash: As of September 30, 2016, Cellectis had €264.0 million in total cash, cash equivalents and current financial assets compared to €269.7 million as of June 30, 2016. This decrease of €5.7 million notably reflects (i) the net cash flows used in operating activities of €1.7 million, which includes €9.2 million of cash receipts in the third quarter of 2016 in connection with the achievement of two milestones under our collaboration agreement with Servier that occurred during the second quarter of 2016, and (ii) capital expenditures of €2.2 million. The change was also attributable to the unrealized negative translation effect of exchange rate fluctuations on our U.S. dollar cash, cash equivalents and current financial assets of €1.6 million.

Revenues and Other Income: During the quarters ended September 30, 2015 and 2016, we recorded €10.0 million and €11.3 million, respectively, in revenues and other income. This is mainly due to (i) the increase of €2.5 million in collaboration revenues, notably due to the agreement to provide Servier with raw materials and batches of UCART19 products, partly offset by (ii) the decrease of €0.3 million in research tax credit and €0.8 million in subsidies.

Total Operating Expenses and Other Operating Income: Total operating expenses and other operating income for the third quarter of 2016 were €22.9 million, compared to €23.4 million for the third quarter of 2015. The non-cash stock-based compensation expenses included in these amounts were €12.1 million and €9.5 million, respectively.

R&D Expenses: For the quarters ended 2015 and 2016, research and development expenses decreased by €2.3 million from €16.2 million in 2015 to €13.8 million in 2016. Personnel expenses decreased by €1.1 million from €10.3 million in 2015 to €9.2 million in 2016, notably due to a €2.5 million decrease in social charges on stock options and free share grants, partly offset by a €0.4 million increase in wages and salaries, and a €0.9 million increase in non-cash stock based compensation expense. Purchases and external expenses and other expenses decreased by €1.2 million from €5.8 million in 2015 to €4.6 million in 2016.

SG&A Expenses: During the quarters ended 2015 and 2016, we recorded €6.9 million and €8.7 million, respectively, of selling, general and administrative expenses. The increase of €1.8 million primarily reflects (i) an increase of €0.9 million in personnel expenses from €5.7 million to €6.7 million, attributable, among other things, to an increase of €1.7 million of non-cash stock-based compensation expense, partly offset by a decrease of €1.0 million of social charges on stock options and free share grants, and (ii) an increase of €0.9 million in purchases and external expenses and other charges.

Financial Gain (Loss): The financial gain was €0.7 million for the third quarter of 2015 compared with a financial loss of €1.0 million for the third quarter of 2016. The change in financial result was primarily attributable to the effect of exchange rate fluctuations on our U.S. dollar cash and cash equivalent accounts.

Net Income (Loss) Attributable to Shareholders of Cellectis: During the three months ended September 30, 2015 and 2016, we recorded a net loss of €12.8 million (or €0.36 per share on both a basic and a diluted basis) and net loss of €12.6 million (or €0.36 per share on both a basic and a diluted basis), respectively. Adjusted loss attributable to shareholders of Cellectis for the third quarter of 2016 was €0.5 million (€0.01 per share on both a basic and a diluted basis) compared to adjusted loss attributable to shareholders of Cellectis of €3.3 million (€0.09 per share on both a basic and a diluted basis), for the third quarter of 2015. Adjusted loss attributable to shareholders of Cellectis for the third quarter of 2016 and 2015 excludes non-cash stock-based compensation expense of €12.1 million and €9.5 million, respectively. Please see "Note Regarding Use of Non-GAAP Financial Measures" for reconciliation of GAAP net income (loss) attributable to shareholders of Cellectis to Adjusted income (loss) attributable to shareholders of Cellectis.

First Nine Months 2016 Financial Results

Cash: As of September 30, 2016, Cellectis had €264.0 million in total cash, cash equivalents and current financial assets compared to € 314.2 million as of December 31, 2015. This decrease of €50.3 million was primarily driven by (i) €30.8 million of cash used in operating activities, notably in connection with the initiation of industrial Good Manufacturing Practice ("GMP") production of UCART123, increased expenses in materials required of GMP production of UCART 123 and other targets, a payment of €7.2 million of value added taxes related to proceeds received in the fourth quarter of 2015 from Servier, partly offset by cash receipts of €9.2 million in connection with the achievement of two milestones under our collaboration agreement with Servier that occurred during the second quarter of 2016 and (ii) €11.3 million of cash used in investment activities, primarily through Calyxt’s land acquisition and greenhouse construction in an aggregate amount of €8.9 million. The decrease was also partially attributable to the negative unrealized translation effect of exchange rate fluctuations on our U.S. dollar cash, cash equivalents and current financial assets accounts of €7.4 million.

Cellectis expects that its cash, cash equivalents and Current financial assets of €264.0 million as of September 30, 2016 will be sufficient to fund its current operations through the end of 2018.

Revenues and Other Income: During the nine-month periods ended September 30, 2015 and 2016, we recorded €27.2 million and €38.9 million, respectively, in revenues and other income. This is mainly due to the increase of (i) €9.6 million in collaboration revenues mainly due to both the agreement to provide Servier with raw materials and additional batches of UCART19 products and the achievement of two milestones (totaling €11.7 million) under our collaboration agreement with Servier and (ii) €3.1 million in research tax credit, partly offset by a decrease of €0.9 million in research subsidies, resulting from the termination of research programs.

Total Operating Expenses and Other Operating Income: Total operating expenses and other operating income for the nine-month period ended September 30, 2016 were €80.9 million, compared to €56.3 million for the nine months ended September 30, 2015. The non-cash stock-based compensation expenses included in these amounts were €39.9 million and €17.5 million, respectively.

R&D Expenses: For the nine months ended September 30, 2015 and 2016, research and development expenses increased by €15.8 million from €36.4 million in 2015 to €52.2 million in 2016. Personnel expenses increased by €8.4 million from €24.3 million in 2015 to €32.7 million in 2016, notably due to a €1.9 million increase in wages and salaries, and a €12.6 million increase in non-cash stock based compensation expense, partly offset by a €6.1 million decrease in social charges on stock options and free share grants. Purchases and external expenses increased by €7.6 million from €11.0 million in 2015 to €18.6 million in 2016, due to increased expenses related to innovation and platform development, including payments to third parties participating in product development, purchases of biological raw materials and expenses associated with the use of laboratories and other facilities.

SG&A Expenses: During the nine months ended September 30, 2015 and 2016, we recorded €19.1 million and €27.8 million, respectively, of selling, general and administrative expenses. The increase of €8.7 million primarily reflects (i) an increase of €7.4 million in personnel expenses from €14.0 million to €21.4 million, attributable, among other things, to a €0.5 million increase in wages and salaries, and an increase of €9.9 million of non-cash stock-based compensation expense, partly offset by a decrease of €3.0 million of social charges on stock options and free share grants, and (ii) an increase of €1.0 million in purchases and external expenses.

Financial Gain (Loss): The financial gain was €0.5 million for the nine months ended September 30, 2015 compared with financial loss of €6.3 million for the nine months ended September 30, 2016. The change in financial result was primarily attributable to the effect of exchange rate fluctuations on our U.S. dollar cash and cash equivalent accounts.

Net Income (Loss) Attributable to Shareholders of Cellectis: During the nine months ended September 30, 2015 and 2016, we recorded a net loss of €28.8 million (or € 0.85 per share on both a basic and a diluted basis) and a net loss of €48.3 million (or €1.37 per share on both a basic and diluted basis), respectively. Adjusted loss attributable to shareholders of Cellectis for the nine months ended September 30, 2016 was €8.4 million (€0.24 per share on both a basic and a diluted basis) compared to adjusted loss attributable to shareholders of Cellectis of € 11.3 million (€0.33 per share on both a basic and a diluted basis), for the nine months ended September 30, 2015. Adjusted loss attributable to shareholders of Cellectis for the nine months ended September 30, 2016 and 2015 excludes a non-cash stock-based compensation expense of €39.9 million and €17.5 million, respectively. Please see "Note Regarding Use of Non-GAAP Financial Measures" for a reconciliation of GAAP net income (loss) attributable to shareholders of Cellectis to Adjusted income (loss) attributable to shareholders of Cellectis.

CELLECTIS S.A.
STATEMENT OF CONSOLIDATED FINANCIAL POSITION
(unaudited)
(€ in thousands, except per share data)

As of
December 31, 2015 September 30, 2016

ASSETS
Non-current assets
Intangible assets 956 1 180
Property, plant, and equipment 5 043 15 141
Other non-current financial assets 845 612
Total non-current assets 6 844 16 933

Current assets
Inventories and accumulated costs on orders in process 158 106
Trade receivables 6 035 11 382
Subsidies receivables 9 102 14 535
Other current assets 4 685 7 252
Cash and cash equivalent and Current financial assets 314 238 263 968
Total current assets 334 218 297 243
TOTAL ASSETS 341 062 314 177

LIABILITIES
Shareholders’ equity
Share capital 1 759 1 767
Premiums related to the share capital 420 682 460 474
Treasury share reserve (184) (373)
Currency translation adjustment (1 631) (1 933)
Retained earnings (137 188) (158 032)
Net income (loss) (20 544) (48 309)
Total shareholders’ equity – Group Share 262 894 253 595
Non-controlling interests 725 1 471
Total shareholders’ equity 263 619 255 066

Non-current liabilities
Non-current financial liabilities 66 37
Non-current provisions 437 581
Total non-current liabilities 503 619

Current liabilities
Current financial liabilities 1 921 1 922
Trade payables 6 611 9 176
Deferred revenues and deferred income 54 758 41 893
Current provisions 953 467
Other current liabilities 12 697 5 034
Total current liabilities 76 940 58 492
TOTAL LIABILITIES AND SHAREHOLDERS’ EQUITY 341 062 314 177

CELLECTIS S.A.
STATEMENT OF CONSOLIDATED OPERATIONS – Third quarter
(unaudited)
(€ in thousands, except per share data)

For the three-month period
ended September 30,
2015 2016

Revenues and other income
Revenues 7 600 10 091
Other income 2 379 1 215
Total revenues and other income 9 978 11 306

Operating expenses and other operating income (expenses)
Royalty expenses (334) (311)
Research and development expenses (1) (16 156) (13 824)
Selling, general and administrative expenses (1) (6 921) (8 712)
Other operating income 0 (6)
Redundancy plan 24 3
Other operating expenses (37) (10)
Total operating expenses and other operating income (expenses) (23 425) (22 860)

Operating income (loss) (13 447) (11 555)

Financial gain (loss) 680 (1 035)

Income (loss) from continuing operations (12 766) (12 590)
Net income (loss) (12 766) (12 590)
Attributable to shareholders of Cellectis (12 766) (12 590)
Attributable to non-controlling interests
–

-

Basic earnings attributable to shareholders of Cellectis per share (€/share) (0.36) (0.36)

Diluted earnings attributable to shareholders of Cellectis per share (€/share) (0.36) (0.36)

___________________

(1) Cellectis reclassified certain expenses related to the year ended December 31, 2015 from SG&A expenses to R&D expenses in the fourth quarter of 2015. This reclassification is effective starting in 2015, and is due to the increased level of efforts towards our R&D activities in order to develop product candidates and work toward clinical phases. Starting in 2015, we classify personnel and other costs related to information technology, human resources, business development, legal, intellectual property and general management in Research and development expense based on the time that employees spent contributing to research and development activities versus general and administrative activities. We approved the reclassification in Q4 2015 and assess the performance of the consolidated company based on this new classification.

CELLECTIS S.A.
STATEMENT OF CONSOLIDATED OPERATIONS – First Nine Months
(unaudited)
(€ in thousands, except per share data)

For the nine-month period
ended September 30,
2015 2016

Revenues and other income
Revenues 23 356 32 892
Other income 3 845 6 053
Total revenues and other income 27 201 38 945

Operating expenses and other operating income (expenses)
Royalty expenses (1 153) (1 035)
Research and development expenses (1) (36 375) (52 220)
Selling, general and administrative expenses (1) (19 145) (27 839)
Other operating income 515 380
Redundancy plan 259 3
Other operating expenses (432) (216)
Total operating expenses and other operating income (expenses) (56 331) (80 926)

Operating income (loss) (29 130) (41 981)

Financial gain (loss) 515 (6 328)

Income (loss) from continuing operations (28 615) (48 309)
Net income (loss) (28 615) (48 309)
Attributable to shareholders of Cellectis (28 786) (48 309)
Attributable to non-controlling interests 171 -

Basic earnings attributable to shareholders of Cellectis per share (€/share) (0.85) (1.37)

Diluted earnings attributable to shareholders of Cellectis per share (€/share) (0.85) (1.37)

___________________

(1) Cellectis reclassified certain expenses related to the year ended December 31, 2015 from SG&A expenses to R&D expenses in the fourth quarter of 2015. This reclassification is effective starting in 2015, and is due to the increased level of efforts towards our R&D activities in order to develop product candidates and work toward clinical phases. Starting in 2015, we classify personnel and other costs related to information technology, human resources, business development, legal, intellectual property and general management in Research and development expense based on the time that employees spent contributing to research and development activities versus general and administrative activities. We approved the reclassification in Q4 2015 and assess the performance of the consolidated company based on this new classification.

Note Regarding Use of Non-GAAP Financial Measures

Cellectis S.A. presents Adjusted Income (Loss) attributable to shareholders of Cellectis in this press release. Adjusted Income (Loss) attributable to shareholders of Cellectis is not a measure calculated in accordance with IFRS. We have included in this press release a reconciliation of this figure to Net Income (Loss) attributable to shareholders of Cellectis, the most directly comparable financial measure calculated in accordance with IFRS. Because Adjusted Income (Loss) attributable to shareholders of Cellectis excludes Non-cash stock-based compensation expense—a non-cash expense, we believe that this financial measure, when considered together with our IFRS financial statements, can enhance an overall understanding of Cellectis’ financial performance. Moreover, our management views the Company’s operations, and manages its business, based, in part, on this financial measure. In particular, we believe that the elimination of Non-cash stock-based expenses from Net Income (Loss) attributable to shareholders of Cellectis can provide a useful measure for period-to-period comparisons of our core businesses. Our use of Adjusted Income (Loss) attributable to shareholders of Cellectis has limitations as an analytical tool, and you should not consider it in isolation or as a substitute for analysis of our financial results as reported under IFRS. Some of these limitations are: (a) other companies, including companies in our industry which use similar stock-based compensation, may address the impact of Non-cash stock-based compensation expense differently; and (b) other companies may report Adjusted Income (Loss) attributable to shareholders or similarly titled measures but calculate them differently, which reduces their usefulness as a comparative measure. Because of these and other limitations, you should consider Adjusted Income (Loss) attributable to shareholders of Cellectis alongside our IFRS financial results, including Net Income (Loss) attributable to shareholders of Cellectis.

RECONCILIATION OF GAAP TO NON-GAAP NET INCOME – Third quarter
(unaudited)
(€ in thousands, except per share data)

For the three-month period
ended September 30,
2015 2016

Net Income (Loss) attributable to shareholders of Cellectis (12 766) (12 590)
Adjustment:
Non-cash stock-based compensation expense
9 464 12 114
Adjusted Income (Loss) attributable to shareholders of Cellectis (3 301) (475)

Basic Adjusted Income (Loss) attributable to shareholders of Cellectis (€/share) (0.09) (0.01)

Weighted average number of outstanding shares, basic (units) 35 094 503 35 333 572

Diluted Adjusted Income (Loss) attributable to shareholders of Cellectis (€/share) (0.09) (0.01)

Weighted average number of outstanding shares, diluted (units) 35 475 034 35 713 432

RECONCILIATION OF GAAP TO NON-GAAP NET INCOME – First nine months
(unaudited)
(€ in thousands, except per share data)

For the nine-month period
ended September 30,

2015 2016

Net Income (Loss) attributable to shareholders of Cellectis (28 786) (48 309)
Adjustment:
Non-cash stock-based compensation expense
17 481 39 911
Adjusted Income (Loss) attributable to shareholders of Cellectis (11 305) (8 398)

Basic Adjusted Income (Loss) attributable to shareholders of Cellectis (€/share) (0.33) (0.24)

Weighted average number of outstanding shares, basic (units) 33 819 191 35 274 890

Diluted Adjusted Income (Loss) attributable to shareholders of Cellectis (€/share) (0.33) (0.24)

Weighted average number of outstanding shares, diluted (units) 34 152 422 35 695 907

As a foreign private issuer, we are not required under the Exchange Act to file periodic reports and financial statements with the SEC as frequently or as promptly as United States companies whose securities are registered under the Exchange Act. Notwithstanding the foregoing, we currently provide quarterly interim consolidated financial data to the SEC, and commencing with our first quarter interim report for the 2017 fiscal year, we intend to file our periodic reports within the deadlines applicable to domestic reporting companies.

On November 22, 2016 NantKwest Inc. (Nasdaq:NK), a pioneering, next-generation, clinical-stage immunotherapy company focused on harnessing the unique power of our immune system using natural killer (NK) cells to treat cancer, infectious diseases and inflammatory diseases, reported that the Company’s abstract reviewing data on the company’s CD19.taNK program has been accepted for an oral presentation at the upcoming 58th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego, CA, December 3-6, 2016 (Press release, NantKwest, NOV 22, 2016, http://ir.nantkwest.com/phoenix.zhtml?c=254059&p=RssLanding&cat=news&id=2225427 [SID1234516781]).

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"NantKwest’s transition from preclinical to clinical studies continues to make significant progress," said Patrick Soon-Shiong, MD, Chairman and CEO of NantKwest. "In these preclinical studies, aNK cells expressing a CD19-CAR (CD19.taNK) demonstrated strong killing of CD19-positive cancer cells. In addition, direct tumor injections of CD19.taNK into a fully immunocompetent mouse model induces tumor clearance and protection from tumor re-challenge, suggesting the induction of a memory (‘vaccine’) protective effect after the injection of the CD19.taNK cell."

Presentation Summary

Intra-Tumor Injection of CAR-Engineered NK Cells Induces Tumor Regression and Protection Against Tumor Re-Challenge

Abstract #466, View Source
Presenter: Laurent Boissel, PhD, NantKwest, Woburn, MA
Sunday, December 4, 2016, 5:15 PM, Room 5AB
This poster will review the potential use of CD19.taNK cells to effectively kill cancer cells. In vivo preclinical studies of direct tumor injection of CD19.taNK cells induces significant tumor regression and significantly improved survival, with 75% of the mice showing complete tumor regression at day 32 (p<0.05). Upon re-challenge with A20 lymphoma cells, >80% mice remained free of tumor after 14 days.

On November 22, 2016 Celgene Corporation (NASDAQ:CELG) reported that data from nearly 350 abstracts, including more than 150 oral presentations, evaluating Celgene investigational agents and investigational uses of marketed products will be presented at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting between Dec. 3-6 in San Diego, California (Press release, Celgene, NOV 22, 2016, View Source [SID1234516753]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Relevant presentations will include investigational data from Celgene agents in company-sponsored and investigator-initiated studies.

"Once again we look forward to an impactful collection of clinical and scientific data at ASH (Free ASH Whitepaper) providing new insights into a broad range of hematologic malignancies," said Michael Pehl, President, Hematology and Oncology for Celgene. "The studies being shared this year underscore our continuing commitment to delivering innovative therapies to patients with serious blood cancers around the world."

Selected abstracts include*:

Multiple Myeloma

Clinical Data on Lenalidomide in Myeloma:

Abstract #241; Oral; Saturday, Dec. 3, 4 p.m., Seaport Ballroom ABCD (Manchester Grand Hyatt) Final Analysis of Overall Survival from the FIRST Trial (Facon)

Abstract #537; Oral; Sunday, Dec. 4, 5 p.m., Room 29 Health related Quality of Life in Patients with Newly Diagnosed Multiple Myeloma Receiving Any or Lenalidomide Maintenance after Autologous Stem Cell Transplant in the Connect MM Disease Registry (Abonour)

Abstract #673; Oral; Monday, Dec. 5, 7 a.m., Seaport Ballroom DE (Manchester Grand Hyatt) Intensification Therapy with Bortezomib-Melphalan-Prednisone Versus Autologous Stem Cell Transplantation for Newly Diagnosed Multiple Myeloma: An Intergroup, Multicenter, Phase III Study of the European Myeloma Network (EMN02/HO95 MM Trial) (Cavo)

Abstract #1143; Oral; Monday, Dec. 5, 5 p.m., Seaport Ballroom ABCD (Manchester Grand Hyatt) Lenalidomide is a Highly-Effective Maintenance Therapy in Myeloma Patients of All Ages; results of the Phase III Myeloma XI Study (Jackson)

Abstract #4497; Poster; Monday, Dec. 5, 6 p.m., Hall GH Pomalidomide + Low-Dose Dexamethasone Following Second-Line Lenalidomide-Based Therapy in Relapsed or Refractory Multiple Myeloma: A Phase 2 Study Investigating Efficacy and Safety (Siegel)

Clinical Data on Pomalidomide in Relapsed/Refractory Myeloma:

Abstract #2119; Poster; Saturday, Dec. 3, 5:30 p.m., Hall GH Pembrolizumab in Combination with Pomalidomide and Dexamethasone (PEMBRO/POM/DEX) for Pomalidomide Exposed Relapsed or Refractory Multiple Myeloma (Wilson)

Abstract #3316; Poster; Sunday, Dec. 4, 6 p.m., Hall GH A Phase I/II Trial of Ixazomib (Ix), Pomalidomide (POM) and Dexamethasone (DEX), in Relapsed/Refractory (R/R) Multiple Myeloma (MM) Patients; Responses in Double Refractory and High Risk Disease (Krishnan)

Abstract #3307; Poster; Sunday, Dec. 4, 6 p.m., Hall GH Selective HDAC6 Inhibitor ACY-241, an Oral Tablet, Combined with Pomalidomide and Dexamethasone: Safety and Efficacy of Escalation and Expansion Cohorts in Patients with Relapsed or Relapsed-and-Refractory Multiple Myeloma (ACE-MM-200 Study) (Niesvizky)

Abstract #1145; Oral; Monday, Dec. 5, 5:30 p.m., Seaport Ballroom BC (Manchester Grand Hyatt) A Multicenter, Open Label Phase I/II Study of Carfilzomib, Pomalidomide and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma (MM) Patients (Bringhen)

Abstract #1151; Oral; Monday, Dec. 5, 5:30 p.m., Hall AB Efficacy of Daratumumab, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma Patients with 1 to 3 Prior Lines of Therapy: Updated Analysis of Pollux (Usmani)

Early Development Initiatives in Myeloma:

Abstract #1591; Poster; Saturday, Dec. 3, 5:30 p.m., Hall GH CC-220 is a Potent Cereblon Modulating Agent that Displays Anti-proliferative, Pro-Apoptotic and Immunomodulatory Activity on Sensitive and Resistant Multiple Myeloma Cell Lines (Bjorklund)

Abstract #1592; Poster; Saturday, Dec. 3, 5:30 p.m., Hall GH CC-122 is a Cereblon Modulating Agent that is Active in Lenalidomide-Resistant and Lenalidomide/Dexamethasone-Double-Resistant Multiple Myeloma Pre-clinical Models (Bjorklund)

Abstract #196; Oral; Saturday, Dec. 3, 2:45 p.m., Grand Hall D (Manchester Grand Hyatt) The Multiple Myeloma Genome Project: Development of a Molecular Segmentation Strategy for the Clinical Classification of Multiple Myeloma (Walker)

Lymphomas/CLL

Lenalidomide Maintenance Data:

Abstract #229; Oral; Saturday, Dec. 3, 4 p.m., Room 5AB Lenalidomide Maintenance after Front Line Therapy Substantially Prolongs Progression Free Survival in High Risk CLL: Interim Results of a Phase 3 Study (CLL M1 study of the German CLL Study Group) (Fink)

Abstract #230; Oral; Saturday, Dec. 3, 4:15 p.m., Room 5AB Results of the Phase III Study of Lenalidomide Versus Placebo as Maintenance Therapy Following Second-Line Treatment for Patients with B-Cell Chronic Lymphocytic Leukemia (the CONTINUUM Trial) (Foa)

Abstract #471; Oral; Sunday, Dec. 4, 5 p.m., Room 6B Final Analysis of an International Double-Blind randomized Phase III Study of Lenalidomide Maintenance in Elderly Patients with DLBCL Treated with R-CHOP in First Line, the REMARC Study from LYSA (Thieblemont)

Lenalidomide Combination Data:

Abstract #1798; Poster; Saturday, Dec. 3, 5:30 p.m., Hall GH MAGNIFY: Phase IIIb Randomized Study of Lenalidomide Plus Rituximab (R2) Followed by Lenalidomide vs. Rituximab Maintenance in Subjects with Relapsed/Refractory Follicular, Marginal Zone, or Mantle Cell Lymphoma (Andorsky)

Abstract #473; Oral; Sunday, Dec. 4, 5:30 p.m., Room 6B A Multicenter Open-Label Phase 1b/2 Study of Ibrutinib in Combination with Lenalidomide and Rituximab in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (Goy)

Abstract #1099; Oral; Monday, Dec. 5, 4:30 p.m., Ballroom 20A Rituximab Plus Lenalidomide Versus Rituximab Monotherapy in Untreated Follicular Lymphoma Patients in Need of Therapy. First Analysis of Survival Endpoints of the Randomized Phase II Trial SAKK 35/10 (Kimby)

Abstract #4199; Poster; Monday, Dec. 5, 6 p.m., Hall GH A Phase 1B Study of CC 122 in Combination with Obinutuzumab (GA101) in Relapsed or Refractory Diffuse Large B-Cell Lymphoma and Indolent Non-Hodgkin Lymphoma (Michot)

Lenalidomide Data in Mantle Cell Lymphoma:

Abstract #1786; Poster; Saturday, Dec. 3, 5:30 p.m., Hall GH Effectiveness of Lenalidomide in Mantle Cell Lymphoma Patients who Relapsed/Progressed After or were Refractory/Intolerant to Ibrutinib: The MCL-004 Study (Wang)

Abstract #4188; Poster; Monday, Dec. 5, 6 p.m., Hall GH CC-122 Exhibits Greater Preclinical Activity in Mantle Cell Lymphoma Than Lenalidomide Through A Combination of Direct Cell-autonomous and Increased Antibody Dependent Cell-mediated Cytotoxicity (Hagner)

Surrogate Outcomes Data:

Abstract #3027; Poster; Sunday, Dec. 4, 6 p.m., Hall GH Utility of Progression-Free Survival at 24 months (PFS24) to Predict Subsequent Outcome for Patients with Diffuse Large B-cell Lymphoma (DLBCL) Enrolled on Randomized Clinical Trials: Findings from a Surrogate Endpoint in Aggressive Lymphoma (SEAL) Analysis of Individual Patient Data (Maurer)

Abstract #1102; Oral; Monday, Dec. 5, 5:15 p.m., Ballroom 20A Outcomes for Elderly Patients with Follicular Lymphoma (FL) Using Individual Patient Data (IPD) from 5922 Patients in 18 Randomized Controlled Trials (RCTs): A FL Analysis of Surrogate Hypothesis (FLASH) Group Study (Flowers)

Abstract #4196; Poster; Monday, Dec. 5, 6 p.m., Hall GH Evaluation of Progression-free Survival (PFS) as a Surrogate Endpoint for Overall Survival (OS) in First-Line Therapy for Diffuse Large B-Cell Lymphoma (DLBCL): Findings from the Surrogate Endpoint in Aggressive Lymphoma (SEAL) Analysis of Individual Patient Data from 7507 Patients (Shi)

MDS/AML/Beta-Thalassemia

Emerging Clinical Data from Investigational cc486, ag221 (enasidenib) and Luspatercept Studies:

Abstract #905; Oral; Monday, Dec. 5, 3:45 p.m., San Diego Ballroom AB (Marriott Marquis San Diego Marina) CC-486 (Oral Azacitidine) in Patients with Hematological Malignancies Who Had Received Prior Treatment with Injectable Hypomethylating Agents (HMAs): Results from Phase 1/2 CC-486 Studies (Garcia-Manero)

Abstract #343; Oral; Sunday, Dec. 4, 9:30 a.m., Grand Hall C (Manchester Grand Hyatt) Enasidenib (AG-221), a Potent Oral Inhibitor of Mutant Isocitrate Dehydrogenase 2 (IDH2) Enzyme, Induces Hematologic Responses in Patients with Myelodysplastic Syndromes (MDS) (Stein)

Abstract #851; Oral; Monday, Dec. 5, 3:45 p.m., Room 7 AB Luspatercept Increases Hemoglobin, Decreases Transfusion Burden and Improves Iron Overload in Adults with Beta-Thalassemia (Piga)

Abstract #3168; Poster; Sunday, Dec. 4, 6 p.m., Hall GH Luspatercept Increases Hemoglobin and Reduces Transfusion Burden in Patients with Low-Intermediate Risk Myelodysplastic Syndromes (MDS): Long-Term results from Phase II PACE-MDS Study (Platzbecker)

The safety and efficacy of the agents and/or uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated.

A complete listing of abstracts can be found on the ASH (Free ASH Whitepaper) Web site at View Source

*All times Pacific Standard Time

About REVLIMID

REVLIMID (lenalidomide) in combination with dexamethasone (dex) is indicated for the treatment of patients with multiple myeloma (MM)

REVLIMID is indicated for the treatment of patients with transfusion-dependent anemia due to low-or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities

REVLIMID is indicated for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib

REVLIMID is not indicated and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials

Important Safety Information

WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, and VENOUS and ARTERIAL THROMBOEMBOLISM

Embryo-Fetal Toxicity

Do not use REVLIMID during pregnancy. Lenalidomide, a thalidomide analogue, caused limb abnormalities in a developmental monkey study. Thalidomide is a known human teratogen that causes severe life-threatening human birth defects. If lenalidomide is used during pregnancy, it may cause birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting REVLIMID treatment. Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after REVLIMID treatment. To avoid embryo-fetal exposure to lenalidomide, REVLIMID is only available through a restricted distribution program, the REVLIMID REMS program (formerly known as the "RevAssist" program).

Information about the REVLIMID REMS program is available at www.celgeneriskmanagement.com or by calling the manufacturer’s toll-free number 1-888-423-5436.

Hematologic Toxicity (Neutropenia and Thrombocytopenia)

REVLIMID can cause significant neutropenia and thrombocytopenia. Eighty percent of patients with del 5q MDS had to have a dose delay/reduction during the major study. Thirty-four percent of patients had to have a second dose delay/reduction. Grade 3 or 4 hematologic toxicity was seen in 80% of patients enrolled in the study. Patients on therapy for del 5q MDS should have their complete blood counts monitored weekly for the first 8 weeks of therapy and at least monthly thereafter. Patients may require dose interruption and/or reduction. Patients may require use of blood product support and/or growth factors.

Venous and Arterial Thromboembolism

REVLIMID has demonstrated a significantly increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as risk of myocardial infarction and stroke in patients with MM who were treated with REVLIMID and dexamethasone therapy. Monitor for and advise patients about signs and symptoms of thromboembolism. Advise patients to seek immediate medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling. Thromboprophylaxis is recommended and the choice of regimen should be based on an assessment of the patient’s underlying risks.

CONTRAINDICATIONS

Pregnancy: REVLIMID can cause fetal harm when administered to a pregnant female and is contraindicated in females who are pregnant. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus

Allergic Reactions: REVLIMID is contraindicated in patients who have demonstrated hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis) to lenalidomide

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity: See Boxed WARNINGS

Females of Reproductive Potential: See Boxed WARNINGS
Males: Lenalidomide is present in the semen of patients receiving the drug. Males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking REVLIMID and for up to 28 days after discontinuing REVLIMID, even if they have undergone a successful vasectomy. Male patients taking REVLIMID must not donate sperm
Blood Donation: Patients must not donate blood during treatment with REVLIMID and for 1 month following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to REVLIMID
REVLIMID REMS Program: See Boxed WARNINGS: Prescribers and pharmacies must be certified with the REVLIMID REMS program by enrolling and complying with the REMS requirements; pharmacies must only dispense to patients who are authorized to receive REVLIMID. Patients must sign a Patient-Physician Agreement Form and comply with REMS requirements; female patients of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements and males must comply with contraception requirements

Hematologic Toxicity: REVLIMID can cause significant neutropenia and thrombocytopenia. Monitor patients with neutropenia for signs of infection. Advise patients to observe for bleeding or bruising, especially with use of concomitant medications that may increase risk of bleeding. MM: Patients taking REVLIMID/dex should have their complete blood counts (CBC) assessed every 7 days for the first 2 cycles, on days 1 and 15 of cycle 3, and every 28 days thereafter. MDS: Patients on therapy for del 5q MDS should have their complete blood counts monitored weekly for the first 8 weeks of therapy and at least monthly thereafter. Patients may require dose interruption and/or dose reduction. Please see the Black Box WARNINGS for further information. MCL: Patients taking REVLIMID for MCL should have their CBCs monitored weekly for the first cycle (28 days), every 2 weeks during cycles 2-4, and then monthly thereafter. Patients may require dose interruption and/or dose reduction

Venous and Arterial Thromboembolism: See Boxed WARNINGS: Venous thromboembolic events (DVT and PE) and arterial thromboses (MI and CVA) are increased in patients treated with REVLIMID. Patients with known risk factors, including prior thrombosis, may be at greater risk and actions should be taken to try to minimize all modifiable factors (e.g., hyperlipidemia, hypertension, smoking). Thromboprophylaxis is recommended and regimen is based on patients underlying risks. ESAs and estrogens may further increase the risk of thrombosis and their use should be based on a benefit-risk decision

Increased Mortality in Patients With CLL: In a clinical trial in the first line treatment of patients with CLL, single agent REVLIMID therapy increased the risk of death as compared to single agent chlorambucil. Serious adverse cardiovascular reactions, including atrial fibrillation, myocardial infarction, and cardiac failure, occurred more frequently in the REVLIMID arm. REVLIMID is not indicated and not recommended for use in CLL outside of controlled clinical trials

Second Primary Malignancies (SPM): In clinical trials in patients with MM receiving REVLIMID, an increase of invasive SPM notably AML and MDS have been observed. Monitor patients for the development of SPMs. Take into account both the potential benefit of REVLIMID and risk of SPMs when considering treatment

Hepatotoxicity: Hepatic failure, including fatal cases, has occurred in patients treated with REVLIMID/dex. Pre-existing viral liver disease, elevated baseline liver enzymes, and concomitant medications may be risk factors. Monitor liver enzymes periodically. Stop REVLIMID upon elevation of liver enzymes. After return to baseline values, treatment at a lower dose may be considered

Allergic Reactions: Angioedema and serious dermatologic reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported. These events can be fatal. Patients with a prior history of Grade 4 rash associated with thalidomide treatment should not receive REVLIMID. REVLIMID interruption or discontinuation should be considered for Grade 2-3 skin rash. REVLIMID must be discontinued for angioedema, Grade 4 rash, exfoliative or bullous rash, or if SJS or TEN is suspected and should not be resumed following discontinuation for these reactions. REVLIMID capsules contain lactose; risk-benefit of treatment should be evaluated in patients with lactose intolerance

Tumor Lysis Syndrome (TLS): Fatal instances of TLS have been reported during treatment with lenalidomide. The patients at risk of TLS are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken

Tumor Flare Reaction (TFR): TFR has occurred during investigational use of lenalidomide for CLL and lymphoma. Monitoring and evaluation of TFR is recommended in patients with MCL. Tumor flare may mimic the progression of disease (PD). In patients with Grade 3 or 4 TFR, it is recommended to withhold treatment with REVLIMID until TFR resolves to ≤ Grade 1. REVLIMID may be continued in patients with Grade 1 and 2 TFR without interruption or modification, at the physician’s discretion

Impaired Stem Cell Mobilization: A decrease in the number of CD34+ cells collected after treatment ( > 4 cycles) with REVLIMID has been reported. Consider early referral to transplant center to optimize timing of the stem cell collection

ADVERSE REACTIONS

Multiple Myeloma

In newly diagnosed: The most frequently reported Grade 3 or 4 reactions included neutropenia, anemia, thrombocytopenia, pneumonia, asthenia, fatigue, back pain, hypokalemia, rash, cataract, lymphopenia, dyspnea, DVT, hyperglycemia, and leukopenia. The highest frequency of infections occurred in Arm Rd Continuous (75%) compared to Arm MPT (56%). There were more grade 3 and 4 and serious adverse reactions of infection in Arm Rd Continuous than either Arm MPT or RD18
The most common adverse reactions reported in ≥20% (Arm Rd Continuous): diarrhea (46%), anemia (44%), neutropenia (35%), fatigue (33%), back pain (32%), asthenia (28%), insomnia (28%), rash, (26%), decreased appetite (23%), cough (23%), dyspnea (22%), pyrexia (21%), abdominal pain (21%), muscle spasms (20%), and thrombocytopenia (20%)
After at least one prior therapy the most common adverse reactions reported in ≥20% (REVLIMID/dex vs dex/placebo): fatigue (44% vs 42%), neutropenia (42% vs 6%), constipation (41% vs 21%), diarrhea (39% vs 27%), muscle cramp (33% vs 21%), anemia (31% vs 24%), pyrexia (28% vs 23%), peripheral edema (26% vs 21%), nausea (26% vs 21%), back pain (26% vs 19%), upper respiratory tract infection (25% vs 16%), dyspnea (24% vs 17%), dizziness (23% vs 17%), thrombocytopenia (22% vs 11%), rash (21% vs 9%), tremor (21% vs 7%), and weight decreased (20% vs 15%)
Myelodysplastic Syndromes

Grade 3 and 4 adverse events reported in ≥ 5% of patients with del 5q MDS were neutropenia (53%), thrombocytopenia (50%), pneumonia (7%), rash (7%), anemia (6%), leukopenia (5%), fatigue (5%), dyspnea (5%), and back pain (5%)
Adverse events reported in ≥15% of del 5q MDS patients (REVLIMID): thrombocytopenia (61.5%), neutropenia (58.8%), diarrhea (49%), pruritus (42%), rash (36%), fatigue (31%), constipation (24%), nausea (24%), nasopharyngitis (23%), arthralgia (22%), pyrexia (21%), back pain (21%), peripheral edema (20%), cough (20%), dizziness (20%), headache (20%), muscle cramp (18%), dyspnea (17%), pharyngitis (16%), epistaxis (15%), asthenia (15%), upper respiratory tract infection (15%)
Mantle Cell Lymphoma

Grade 3 and 4 adverse events reported in ≥5% of patients treated with REVLIMID in the MCL trial (N=134) included neutropenia (43%), thrombocytopenia (28%), anemia (11%), pneumonia (9%), leukopenia (7%), fatigue (7%), diarrhea (6%), dyspnea (6%), and febrile neutropenia (6%)
Adverse events reported in ≥15% of patients treated with REVLIMID in the MCL trial included neutropenia (49%), thrombocytopenia (36%), fatigue (34%), anemia (31%), diarrhea (31%), nausea (30%), cough (28%), pyrexia (23%), rash (22%), dyspnea (18%), pruritus (17%), peripheral edema (16%), constipation (16%), and leukopenia (15%)
DRUG INTERACTIONS

Periodic monitoring of digoxin plasma levels is recommended due to increased Cmax and AUC with concomitant REVLIMID therapy. Patients taking concomitant therapies such as erythropoietin stimulating agents or estrogen containing therapies may have an increased risk of thrombosis. It is not known whether there is an interaction between dex and warfarin. Close monitoring of PT and INR is recommended in MM patients taking concomitant warfarin

NURSING MOTHERS

Discontinue drug or nursing taking into consideration the importance of the drug to the mother

PEDIATRIC USE

Safety and effectiveness in patients below the age of 18 have not been established

RENAL IMPAIRMENT

REVLIMID is primarily excreted unchanged by the kidneys; adjustments to the starting dose are recommended to provide appropriate drug exposure in patients with moderate or severe renal impairment and in patients on dialysis

Please see full Prescribing Information, including Boxed WARNINGS.

About POMALYST/IMNOVID

Indication

POMALYST (pomalidomide) is a thalidomide analogue indicated, in combination with dexamethasone, for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy.

Important Safety Information

WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL THROMBOEMBOLISM
Embryo-Fetal Toxicity

POMALYST is contraindicated in pregnancy. POMALYST is a thalidomide analogue. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting POMALYST treatment.
Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping POMALYST treatment.
POMALYST is only available through a restricted distribution program called POMALYST REMS.
Venous and Arterial Thromboembolism

Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in patients with multiple myeloma treated with POMALYST. Prophylactic antithrombotic measures were employed in clinical trials. Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient’s underlying risk factors.

CONTRAINDICATIONS

Pregnancy: POMALYST can cause fetal harm and is contraindicated in females who are pregnant. If POMALYST is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to a fetus.
WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity & Females of Reproductive Potential: See Boxed WARNINGS
Males: Pomalidomide is present in the semen of patients receiving the drug. Males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 4 weeks after discontinuing POMALYST, even if they have undergone a successful vasectomy. Males must not donate sperm.
Blood Donation: Patients must not donate blood during treatment with POMALYST and for 1 month following discontinuation of POMALYST therapy because the blood might be given to a pregnant female patient whose fetus must not be exposed to POMALYST.
POMALYST REMS Program: See Boxed WARNINGS
Prescribers and pharmacies must be certified with the POMALYST REMS program by enrolling and complying with the REMS requirements; pharmacies must only dispense to patients who are authorized to receive POMALYST. Patients must sign a Patient-Physician Agreement Form and comply with REMS requirements; female patients of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements and males must comply with contraception requirements.
Further information about the POMALYST REMS program is available at www.CelgeneRiskManagement.com or by telephone at 1-888-423-5436.
Venous and Arterial Thromboembolism: See Boxed WARNINGS. Patients with known risk factors, including prior thrombosis, may be at greater risk, and actions should be taken to try to minimize all modifiable factors (e.g., hyperlipidemia, hypertension, smoking). Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient’s underlying risk factors.
Hematologic Toxicity: Neutropenia (46%) was the most frequently reported Grade 3/4 adverse reaction in patients taking POMALYST in clinical trials, followed by anemia and thrombocytopenia. Monitor complete blood counts weekly for the first 8 weeks and monthly thereafter. Patients may require dose interruption and/or modification.
Hepatotoxicity: Hepatic failure, including fatal cases, has occurred in patients treated with POMALYST. Elevated levels of alanine aminotransferase and bilirubin have also been observed in patients treated with POMALYST. Monitor liver function tests monthly. Stop POMALYST upon elevation of liver enzymes. After return to baseline values, treatment at a lower dose may be considered.
Hypersensitivity Reactions: Angioedema and severe dermatologic reactions have been reported. Discontinue POMALYST for angioedema, skin exfoliation, bullae, or any other severe dermatologic reactions, and do not resume therapy.
Dizziness and Confusional State: In patients taking POMALYST in clinical trials, 14% experienced dizziness (1% Grade 3 or 4) and 7% a confusional state (3% Grade 3 or 4). Instruct patients to avoid situations where dizziness or confusional state may be a problem and not to take other medications that may cause dizziness or confusional state without adequate medical advice.
Neuropathy: In patients taking POMALYST in clinical trials, 18% experienced neuropathy (2% Grade 3 in one trial) and 12% peripheral neuropathy.
Second Primary Malignancies: Cases of acute myelogenous leukemia have been reported in patients receiving POMALYST as an investigational therapy outside of multiple myeloma.
Tumor Lysis Syndrome (TLS): TLS may occur in patients treated with POMALYST. Patients at risk are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken.
ADVERSE REACTIONS

Nearly all patients treated with POMALYST + low-dose dex experienced at least one adverse reaction (99%). The most common adverse reactions included neutropenia (51.3%), fatigue and asthenia (46.7%), upper respiratory tract infection (31%), thrombocytopenia (29.7%), pyrexia (26.7%), dyspnea (25.3%), diarrhea (22%), constipation (21.7%), back pain (19.7%), cough (20%), pneumonia (19.3%), bone pain (18%), edema peripheral (17.3%), peripheral neuropathy (17.3%), muscle spasms (15.3%), and nausea (15%). Grade 3 or 4 adverse reactions included neutropenia (48.3%), thrombocytopenia (22%), and pneumonia (15.7%).

DRUG INTERACTIONS

Avoid concomitant use of POMALYST with strong inhibitors of CYP1A2. Consider alternative treatments. If a strong CYP1A2 inhibitor must be used, reduce POMALYST dose by 50%.

USE IN SPECIFIC POPULATIONS

Pregnancy: See Boxed WARNINGS. If pregnancy does occur during treatment, immediately discontinue the drug and refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. There is a POMALYST pregnancy exposure registry that monitors pregnancy outcomes in females exposed to POMALYST during pregnancy as well as female partners of male patients who are exposed to POMALYST. This registry is also used to understand the root cause for the pregnancy. Report any suspected fetal exposure to POMALYST to the FDA via the MedWatch program at 1-800-FDA-1088 and also to Celgene Corporation at 1-888-423-5436.
Lactation: There is no information regarding the presence of pomalidomide in human milk, the effects of POMALYST on the breastfed infant, or the effects of POMALYST on milk production. Pomalidomide was excreted in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed infants from POMALYST, advise a nursing woman to discontinue breastfeeding during treatment with POMALYST.
Pediatric Use: Safety and effectiveness have not been established in pediatric patients.
Geriatric Use: No dosage adjustment is required for POMALYST based on age. Patients > 65 years of age were more likely than patients ≤65 years of age to experience pneumonia.
Renal Impairment: Reduce POMALYST dose by 25% in patients with severe renal impairment requiring dialysis. Take dose of POMALYST following hemodialysis on hemodialysis days.
Hepatic Impairment: Reduce POMALYST dose by 25% in patients with mild to moderate hepatic impairment and 50% in patients with severe hepatic impairment.
Smoking Tobacco: Advise patients that smoking may reduce the efficacy of POMALYST. Cigarette smoking reduces the AUC of pomalidomide by 32% by CYP1A2 induction.
Please see full Prescribing Information, including Boxed WARNINGS.

On November 22, 2016 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported that new data regarding the investigational use of KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, in patients with a range of blood cancers including classical Hodgkin lymphoma and primary mediastinal large B-cell lymphoma, will be presented at the 58th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego, Dec. 3-6 (Press release, Merck & Co, NOV 22, 2016, View Source [SID1234516757]).

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"There is an urgent need for new treatment approaches in blood cancers, especially for those patients who have relapsed or not responded to current therapies," said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. "We hope to learn that PD-1-directed immunotherapy may be used to help patients suffering from these difficult to treat malignancies."

The KEYTRUDA clinical development program includes more than 30 tumor types in more than 360 clinical trials, including over 200 trials that combine KEYTRUDA with other cancer treatments. For hematologic malignancies specifically, Merck is conducting broad immuno-oncology research assessing the role of monotherapy and combination regimens with KEYTRUDA. The program includes nearly 40 ongoing studies – several of which are registration-enabling trials – across more than 20 hematologic disease subtypes, including leukemia, lymphomas, and myeloma.

Below is a select list of KEYTRUDA data to be featured in oral presentations (all at the San Diego Convention Center):

(Abstract #1107) Pembrolizumab in Relapsed/Refractory Classical Hodgkin Lymphoma: Primary End Point Analysis of the Phase 2 Keynote-087 Study. C. Moskowitz. Monday, Dec. 5, 5 p.m. PST (session: 4:30-6 p.m. PST). Location: Room 6B.
(Abstract #1108) Pembrolizumab in Patients with Classical Hodgkin Lymphoma after Brentuximab Vedotin Failure: Long-Term Efficacy from the Phase 1b Keynote-013 Study. P. Armand. Monday, Dec. 5, 5:15 p.m. PST (session: 4:30-6 p.m. PST). Location: Room 6B.
(Abstract #619) Phase 1b Study of Pembrolizumab in Patients with Relapsed/Refractory Primary Mediastinal Large B-Cell Lymphoma: Results from the Ongoing Keynote-013 Trial. P. Zinzani. Monday, Dec. 5, 7 a.m. PST (session: 7-8:30 a.m. PST). Location: Room 6B.
Additional meeting information and full abstracts are available on the ASH (Free ASH Whitepaper) meeting website.

About KEYTRUDA (pembrolizumab)

KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

KEYTRUDA is administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. KEYTRUDA for injection is supplied in a 100 mg single use vial.

KEYTRUDA Indications and Dosing

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a dose of 2 mg/kg every three weeks until disease progression or unacceptable toxicity.

Lung Cancer

KEYTRUDA is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA (pembrolizumab) is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In HNSCC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%) pneumonitis, and occurred more frequently in patients with a history of prior thoracic radiation (6.9%) compared to those without (2.9%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 48 (1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

KEYTRUDA (pembrolizumab) can cause immune-mediated hepatitis. Hepatitis occurred in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.

KEYTRUDA can cause thyroid disorders, including hyperthyroidism, hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799 patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in patients with HNSCC occurring in 28 (15%) of 192 patients with HNSCC, including Grade 3 (0.5%) hypothyroidism. Thyroiditis occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.3%) thyroiditis. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.

KEYTRUDA can cause type 1 diabetes mellitus, including diabetic ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 9 (0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.

KEYTRUDA can cause other clinically important immune-mediated adverse reactions. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA (pembrolizumab) and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), exfoliative dermatitis, bullous pemphigoid, rash (1.4%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma.

KEYTRUDA can cause severe or life-threatening infusion-related reactions, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for signs and symptoms of infusion-related reactions, including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). Adverse reactions leading to interruption of KEYTRUDA occurred in 21% of patients; the most common (≥1%) was diarrhea (2.5%). The most common adverse reactions with KEYTRUDA vs ipilimumab were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs 23%), and nausea (21% with KEYTRUDA). Corresponding incidence rates are listed for ipilimumab only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.

In KEYNOTE-002, KEYTRUDA was discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (≥1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). Adverse reactions leading to interruption of KEYTRUDA occurred in 14% of patients; the most common (≥1%) were dyspnea (1%), diarrhea (1%), and maculopapular rash (1%). The most common adverse reactions with KEYTRUDA (pembrolizumab) vs chemotherapy were fatigue (43% with KEYTRUDA), pruritus (28% vs 8%), rash (24% vs 8%), constipation (22% vs 20%), nausea (22% with KEYTRUDA), diarrhea (20% vs 20%), and decreased appetite (20% with KEYTRUDA). Corresponding incidence rates are listed for chemotherapy only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.

KEYTRUDA was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC. The most common adverse event resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.8%). Adverse reactions leading to interruption of KEYTRUDA occurred in 23% of patients; the most common (≥1%) were diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme elevation (1.2%), decreased appetite (1.3%), and pneumonitis (1%). The most common adverse reactions (occurring in at least 20% of patients and at a higher incidence than with docetaxel) were decreased appetite (25% vs 23%), dyspnea (23% vs 20%), and nausea (20% vs 18%).

KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (reported in at least 20% of patients) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC, with the exception of increased incidences of facial edema (10% all Grades; 2.1% Grades 3 or 4) and new or worsening hypothyroidism.

It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.

Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.

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