On May 16, 2018 Eleven Biotherapeutics, Inc. (Nasdaq: EBIO), a late-stage clinical company developing next-generation antibody-drug conjugate (ADC) therapies for the treatment of cancer, reported that the company is changing its name to Sesen Bio, Inc. Sesen Bio will trade under the new Nasdaq ticker symbol "SESN," effective on May 17, 2018 (Press release, Eleven Biotherapeutics, MAY 16, 2018, View Source [SID1234526820]). The former ticker symbol "EBIO" will remain effective through the market close on May 16, 2018. The new website for Sesen Bio is www.sesenbio.com.

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Additionally, the company announced the appointments of Hagop Youssoufian, M.Sc., M.D. as senior medical advisor and Madhu Anant M.Sc., Ph.D., RAC as vice president of regulatory affairs.

"Over the last several years, we have undergone an incredible transformation as a company, and our new name, Sesen Bio, reinforces this evolution and our focused commitment to oncology drug development. Sesen, an ancient symbol of the lotus flower, represents life and our mission to bring forward medicines that will improve and preserve the lives of those with devastating cancers," said Stephen Hurly, president and chief executive officer of Sesen Bio. "The additions of Dr. Youssoufian and Dr. Anant further strengthen our leadership team and drug development capabilities as we work to bring our lead asset, Vicinium, through Phase 3 development for high-grade non-muscle invasive bladder cancer and advance regulatory interactions. 2018 is set to be a significant year for Sesen Bio, as we are well on our way to achieving our vision and bettering the lives of people in need."

Dr. Youssoufian joins Sesen Bio as senior medical advisor with more than 25 years of physician and drug development experience. He has spent over a decade serving as a consultant to more than 100 biotech companies and investment funds, acting in various roles including chief medical officer, clinical monitor and regulatory officer. In his career, Dr. Youssoufian has led a successful U.S. Food and Drug Administration advisory committee meeting and worked on numerous approved treatments, including Sprycel, Taxotere, Erbitux, Cyramza and Lartruvo. Prior to Sesen Bio, Dr. Youssoufian served as chief medical officer for Bind Therapeutics, where he was responsible for all clinical and regulatory programs, including interactions with key opinion leaders, investors and analysts; executive vice president of research and development for Progenics Pharmaceuticals; president of research and development and chief medical officer for Ziopharm Oncology; and chief medical officer at ImClone-Lilly. Dr. Youssoufian earned his M.D. and M.Sc. from the University of Massachusetts Medical School. He is a medical oncologist and geneticist and an elected member of the American Society for Clinical Investigation.

Dr. Anant brings more than 35 years of experience to her role as vice president of regulatory affairs at Sesen Bio. Prior to joining Sesen Bio, she served as the vice president, global regulatory affairs, hospital products for Mallinckrodt Pharmaceuticals where she was responsible for all regulatory activities including, strategy, health authority liaisons and regulatory pathways for development of products. Prior to Mallinckrodt, Dr. Anant served as an independent consultant in numerous roles including, head of regulatory affairs and lead strategist in regulatory affairs, clinical development and medical affairs. Earlier, she served as director, global regulatory sciences, geographic optimization for Bristol-Myers Squibb. There, she led the global regulatory strategies for geographic optimization of mature brands in the cardiovascular, metabolic, anti-infective and oncology therapeutic areas. Dr. Anant earned her Ph.D. from the International University for Professional Studies and her M.Sc. from the Institute of Science in Nagpur, India.

About Vicinium
Vicinium, also known as VB4-845, is Sesen Bio’s lead product candidate and is a next-generation antibody-drug conjugate (ADC), developed using the company’s proprietary Targeted Protein Therapeutics platform, for the treatment of high-grade non-muscle invasive bladder cancer (NMIBC). Vicinium is comprised of a recombinant fusion protein that targets epithelial cell adhesion molecule (EpCAM) antigens on the surface of tumor cells to deliver a potent protein payload, Pseudomonas Exotoxin A (ETA). Vicinium is constructed with a stable, genetically engineered peptide linker to ensure the payload remains attached until it is internalized by the cancer cell, which is believed to decrease the risk of toxicity to healthy tissues, thereby improving its safety. In prior clinical studies conducted by Sesen Bio, EpCAM has been shown to be overexpressed in NMIBC cells with minimal to no EpCAM expression observed on normal bladder cells. Sesen Bio is currently conducting the Phase 3 VISTA Trial, designed to support the registration of Vicinium for the treatment of high-grade NMIBC in patients who have previously received two courses of bacillus Calmette-Guérin (BCG) and whose disease is now BCG-unresponsive. Three-month data from the ongoing trial are planned for presentation at the 2018 American Urological Association Annual Meeting on May 21, 2018, with 12-month data anticipated in mid-2019. Additionally, Sesen Bio believes that Vicinium’s cancer cell-killing properties promote an anti-tumor immune response that may potentially combine well with immuno-oncology drugs, such as checkpoint inhibitors. The activity of Vicinium in BCG-unresponsive NMIBC is also being explored at the US National Cancer Institute in combination with AstraZeneca’s immune checkpoint inhibitor durvalumab.

On May 16, 2018 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported the Company has gained access to additional intellectual property from Memorial Sloan Kettering Cancer Center (MSK) that enables the development of gene-edited T-cell immunotherapies (Press release, Fate Therapeutics, MAY 16, 2018, View Source [SID1234526802]). The newly-licensed portfolio of intellectual property covers new chimeric antigen receptor (CAR) constructs as well as off-the-shelf CAR T cells, including the use of CRISPR and other innovative technologies for their production.

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Fate Therapeutics is utilizing gene editing under its ongoing collaboration for the research and development of off-the-shelf CAR T-cell immunotherapies with Michel Sadelain, M.D., Ph.D., Director of the Center for Cell Engineering and the Stephen and Barbara Friedman Chair at MSK. At the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting, Dr. Sadelain will present preclinical data on FT819, an off-the-shelf, TCR-less, CD19 CAR T-cell product manufactured from a clonal master induced pluripotent stem cell (iPSC) line.

"Engineering stem cells and using master iPSC lines for the renewable production of off-the-shelf CAR T cells has the potential to advance the cancer immunotherapy landscape," said Dr. Sadelain. "We are pleased with the breakthrough discoveries accomplished under our ongoing collaboration with Fate Therapeutics, and look forward to continuing our advancement together of off-the-shelf CAR T-cell products toward clinical development."

The use of clonal master iPSC lines can overcome the complexity, heterogeneity and substantial costs associated with using cells from a patient or an allogeneic donor. Instead, iPSC-derived T-cell immunotherapies can be consistently and repeatedly mass produced and delivered in an off-the-shelf manner, significantly reducing the cost of, and time to, patient treatment.

"The use of a gene-edited master iPSC line for the manufacture of off-the-shelf T-cell immunotherapies ensures complete removal of endogenous TCR expression, which is critical to avoid the life-threatening complication of graft-versus-host disease that is seen in allogeneic T-cell therapy," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "The incorporation of these latest MSK technologies into our development of FT819 and our iPSC product platform advances our leadership

position in developing off-the-shelf T-cell immunotherapies with improved safety, enhanced potency and expanded therapeutic reach."

Fate Therapeutics has exclusively licensed from MSK intellectual property covering the production and composition of iPSC-derived T cells for human therapeutic use. In addition, Fate Therapeutics owns an extensive intellectual property portfolio that broadly covers compositions and methods for the genome editing of iPSCs using CRISPR and other nucleases, including the use of CRISPR to insert a CAR in the TRAC locus for endogenous transcriptional control.

About FT819

FT819 is a universal, off-the-shelf, dual-targeted CAR T-cell product that is manufactured from a clonal master iPSC line. The line is engineered to completely eliminate expression of the T-cell receptor, to preferentially regulate CAR19 expression by inserting the CAR into the T-cell receptor constant (TRAC) locus, and to uniquely express a recombinant CD16 Fc receptor. In preclinical studies, FT819 exhibits a target-specific T-cell response in vitro when challenged with CD19-positive tumor cells and displays enhanced production of effector cytokines and cytolytic proteins. In addition, FT819 uniquely elicits antibody-dependent cell-mediated cytotoxicity in vitro against CD19-negative, CD20-positive tumor cells with rituximab, a monoclonal antibody targeting CD20. This dual-targeted approach of FT819 can substantially broaden the cell product’s therapeutic reach and overcome CD19 antigen escape through combination with other proven cancer treatments.

On May 16, 2018 Array BioPharma Inc. (Nasdaq: ARRY) reported that it will present data from the Phase 3 COLUMBUS trial of encorafenib and binimetinib in advanced BRAF-mutant melanoma in an oral presentation on June 4, 2018, at the 54th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago, Illinois (Press release, Array BioPharma, MAY 16, 2018, View Source [SID1234526780]).

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"Binimetinib and encorafenib is the first targeted therapy to demonstrate over 30 months median overall survival in a Phase 3 trial and we look forward to presenting the results from the COLUMBUS trial at ASCO (Free ASCO Whitepaper)," said Ron Squarer, Chief Executive Officer. "With nearly 15 months median progression-free survival and an attractive tolerability profile, these data underscore the potential of this combination to become an important new treatment option for patients with BRAF-mutant advanced, unresectable or metastatic melanoma."

As previously announced, the most common Grade 3/4 adverse events (AEs) seen in more than 5% of patients were increased gamma-glutamyltransferase (GGT) (9%), increased creatine phosphokinase (7%), and hypertension (6%) in the encorafenib plus binimetinib group.

Oral Presentation:

Title:

Overall Survival in COLUMBUS: A Phase 3 Trial of Encorafenib (ENCO) Plus Binimetinib (BINI) vs Vemurafenib (VEM) or ENCO in BRAF-Mutant Melanoma

Presenter:

Reinhard Dummer, M.D.

Abstract:

Abstract #223875/Publication #9504

Session:

Melanoma/Skin Cancers

Date:

Monday, June 4, 2018

Time:

9:12 a.m. – 9:24 a.m. Central Time (10:12 a.m. – 10:24 a.m. Eastern Time)

Location:

Arie Crown Theater

The abstract can be accessed through the ASCO (Free ASCO Whitepaper) website, View Source, beginning May 16, 2018, at 5:00 p.m. Eastern Time. Following the presentation on June 4, the slides will be available as a PDF on Array’s website at www.arraybiopharma.com.

Array will host an encore webcast presentation of the COLUMBUS trial data.

Encore Webcast:

Date:

Monday, June 4, 2018

Time:

11:15 a.m. Central Time (12:15 p.m. Eastern Time)

Toll-Free:

(844) 464-3927

Toll:

(765) 507-2598

Pass Code:

9615719

Webcast, including replay and conference call slides:View Source

About Melanoma
Metastatic melanoma is the most serious and life-threatening type of skin cancer and is associated with low survival rates. [1, 2] There are about 200,000 new cases of melanoma diagnosed worldwide each year, approximately half of which have BRAF mutations, a key target in the treatment of metastatic melanoma. [1, 3, 4]

About COLUMBUS
The COLUMBUS trial, (NCT01909453), is a two-part, international, randomized, open label Phase 3 trial evaluating the efficacy and safety of the combination of encorafenib and binimetinib compared to vemurafenib and encorafenib monotherapy in 921 patients with locally advanced, unresectable or metastatic melanoma with BRAFV600 mutation. Prior immunotherapy treatment was allowed. Over 200 sites across North America, Europe, South America, Africa, Asia and Australia participated in the trial. Patients were randomized into two parts:

In Part 1, 577 patients were randomized 1:1:1 to receive the combination of encorafenib 450 mg daily and binimetinib 45 mg twice daily (COMBO450), encorafenib, 300 mg daily (ENCO 300), or vemurafenib, 960 mg twice daily alone. The dose of encorafenib in the combination arm is 50% higher than the single agent maximum tolerated dose of 300 mg. A higher dose of encorafenib was possible due to improved tolerability when combined with binimetinib. The primary endpoint for the COLUMBUS trial was an mPFS comparison of the COMBO450 arm versus vemurafenib. mPFS is determined based on tumor assessment (RECIST version 1.1 criteria) by a Blinded Independent Central Review (BICR). Secondary endpoints include a comparison of the mPFS of COMBO450 arm to that of ENCO300 and a comparison of overall survival (OS) in patients treated in the COMBO450 arm to that of vemurafenib alone. Results from Part 1 of the COLUMBUS trial, previously published in The Lancet OncologyMay 2018, showed that COMBO450 more than doubled mPFS in patients with advanced BRAF-mutant melanoma, with a mPFS of 14.9 months compared with 7.3 months observed with vemurafenib [HR 0.54, (95% CI 0.41-0.71, p<0.0001)]. In the secondary mPFS comparison of COMBO450 to ENCO300, ENCO300 demonstrated a mPFS of 9.6 months [HR 0.75, (95% CI 0.56-1.00, p=0.051)].
In Part 2, 344 patients were randomized 3:1 to receive encorafenib 300 mg daily plus binimetinib 45 mg twice daily (COMBO300) or ENCO300. Part 2 was designed to provide additional data to help evaluate the contribution of binimetinib to the combination of encorafenib and binimetinib.
As the secondary endpoint comparison of mPFS between the COMBO450 arm and ENCO300 arm in Part 1 did not achieve statistical significance, the protocol specified analysis of OS is descriptive.

About Encorafenib and Binimetinib
BRAF and MEK are key protein kinases in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Research has shown this pathway regulates several key cellular activities including proliferation, differentiation, survival and angiogenesis. Inappropriate activation of proteins in this pathway has been shown to occur in many cancers including melanoma and colorectal cancer. Encorafenib is a late-stage small molecule BRAF inhibitor and binimetinib is a late-stage small molecule MEK inhibitor, both of which target key enzymes in this pathway. Encorafenib and binimetinib are being studied in clinical trials in advanced cancer patients, including the Phase 3 COLUMBUS trial and the Phase 3 BEACON CRC trial.

Array BioPharma has exclusive rights to encorafenib and binimetinib in the U.S. and Canada. Array has granted Ono Pharmaceutical exclusive rights to commercialize both products in Japan and South Korea and Pierre Fabre exclusive rights to commercialize both products in all other countries, including Europe, Asia and Latin America. Encorafenib and binimetinib are investigational medicines and are not currently approved in any country.

On May 16, 2018 The Janssen Pharmaceutical Companies of Johnson & Johnson reported 21 company-sponsored abstracts will be presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL on June 1-5 (Press release, Johnson & Johnson, MAY 16, 2018, View Source [SID1234526768]). New data analyses in support of a portfolio of products, including the investigational treatment erdafitinib, IMBRUVICA (ibrutinib), DARZALEX (daratumumab), ERLEADA (apalutamide) and ZYTIGA (abiraterone acetate), will be highlighted across urothelial, hematologic and prostate cancers.

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Notably, Phase 2 trial results for the investigational compound erdafitinib, which received U.S. Food and Drug Administration (FDA) Breakthrough Therapy Designation, will be presented during an Oral Presentation on Sunday, June 3 (Abstract #4503). For hematologic cancers, Phase 3 data from the iNNOVATE study will provide the first look at IMBRUVICA plus rituximab versus placebo plus rituximab in patients with newly diagnosed and relapsed/refractory Waldenström’s macroglobulinemia (WM) (Abstract #8003). In addition, Phase 2 data from the CAPTIVATE study will be presented evaluating IMBRUVICA plus venetoclax in first-line chronic lymphocytic leukemia (CLL) (Abstract #7502). Oral Presentations for erdafitinib and IMBRUVICA have been selected to be featured at the Best of ASCO (Free ASCO Whitepaper) 2018 Meetings, which highlight cutting-edge science and reflect the leading research and strategies in oncology.

"We look forward to presenting the latest data from our robust oncology portfolio, which includes four innovative medicines that our expert team of scientists have developed to address the needs of patients living with hematologic malignancies or prostate cancer," said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. "In addition, new data for erdafitinib, a promising investigational therapy that received Breakthrough Therapy Designation for metastatic urothelial cancer from the U.S. FDA earlier this year, will be featured in an oral presentation, as one of several noteworthy selections from the portfolio."

Select data presentations include:

Erdafitinib: Results from the primary analysis of the Phase 2 study of erdafitinib (ERDA; JNJ-42756493) in patients with metastatic or unresectable urothelial carcinoma (mUC) and Fibroblast Growth Factor Receptor alterations (FGFRalt).
These data will be featured in an Oral Presentation from 9:00 – 9:12 a.m. CDT on Sunday, June 3 (Abstract #4503) and have been selected for the Best of ASCO (Free ASCO Whitepaper) 2018 Meetings.
IMBRUVICA: Findings from the Phase 3 placebo-controlled iNNOVATE study will be presented, assessing IMBRUVICA plus rituximab versus placebo plus rituximab in patients with newly diagnosed and relapsed/refractory WM.*
These data will be featured in an Oral Presentation from 3:45 – 3:57 p.m. CDT on Friday, June 1 (Abstract #8003) and have been selected for the Best of ASCO (Free ASCO Whitepaper) 2018 Meetings.
IMBRUVICA: Early results from the Phase 2 CAPTIVATE study will be presented, evaluating IMBRUVICA in combination with venetoclax in first-line CLL.*
These data will be featured in an Oral Presentation from 10:09 – 10:21 a.m. CDT on Sunday, June 3 (Abstract #7502) and have been selected for the Best of ASCO (Free ASCO Whitepaper) 2018 Meetings.
DARZALEX: Phase 1 data from the MMY1001 study will report on the efficacy and safety of DARZALEX in combination with carfilzomib and dexamethasone in lenalidomide-refractory patients with relapsed multiple myeloma.
These data will be presented in an Oral Presentation from 3:09 – 3:21 p.m. CDT on Friday, June 1 (Abstract #8002).
DARZALEX: Follow-up efficacy and safety data from the pivotal Phase 3 ALCYONE study will be presented for DARZALEX in combination with bortezomib, melphalan and prednisone in patients with newly diagnosed multiple myeloma who are transplant ineligible.
These data will be presented in a Poster Presentation from 8:00 – 11:30 a.m. CDT on Monday, June 4 (Abstract #8031).
DARZALEX: Safety run-in results from the Phase 3 ANDROMEDA study will be presented evaluating the subcutaneous use of daratumumab in combination with cyclophosphamide, bortezomib and dexamethasone in patients with newly diagnosed amyloid light chain (AL) amyloidosis. Amyloidosis is an incurable disease in which cells that normally produce antibodies make an abnormal protein that deposits in and causes damage to organs, such as the heart and kidneys.1
These data will be presented in a Poster Discussion Presentation from 3:00 – 4:15 p.m. CDT on Monday, June 4 (Abstract #8011).
ERLEADA: New analyses from the pivotal Phase 3 SPARTAN clinical trial will be presented examining the relationship between time to metastasis (TTM) and site of metastases in patients with non-metastatic castration-resistant prostate cancer (nmCRPC).
These data will be presented in a Poster Presentation from 1:15 – 4:45 p.m. CDT on Saturday, June 2 (Abstract #5033).
ZYTIGA: New findings from the pivotal Phase 3 LATITUDE clinical trial in patients with metastatic high-risk castration-sensitive prostate cancer (CSPC) will be presented.
These data will be presented in a Poster Presentation from 1:15 – 4:45 p.m. CDT on Saturday, June 2 (Abstract #5028).
Prostate Cancer: New analysis exploring the association between metastasis-free survival (MFS) and overall survival (OS) will be presented in nmCRPC for the first time.
These data will be presented in a Poster Presentation from 1:15 – 4:45 p.m. CDT on Saturday, June 2 (Abstract #5032).
Additional abstracts to be presented include:

Abstract No.

Title

Date/Time

Erdafitinib

Abstract #4503

First results from the primary analysis population of the Phase 2 study of erdafitinib (ERDA; JNJ-42756493) in patients (pts) with metastatic or unresectable urothelial carcinoma (mUC) and FGFR alterations (FGFRalt)

Oral Presentation

Sunday, June 3

9:00 – 9:12 a.m. CDT

IMBRUVICA*

Abstract #8003

Randomized Phase 3 trial of ibrutinib/rituximab vs rituximab in Waldenstrom’s macroglobulinemia

Oral Presentation

Friday, June 1

3:45 – 3:57 p.m. CDT

Abstract #7502

Phase 2 CAPTIVATE results of ibrutinib (ibr) plus venetoclax (ven) in first-line chronic lymphocytic leukemia (CLL)

Oral Presentation

Sunday, June 3

10:09 – 10:21 a.m. CDT

Abstract #7521

Prognostic role of beta-2 microglobulin (B2M) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) patients (pts) treated with ibrutinib (ibr)

Poster Session

Monday, June 4

8:00 – 11:30 a.m. CDT

Abstract #2578

A multicenter study of the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib plus durvalumab in patients with relapsed/refractory (R/R) solid tumors

Poster Session

Monday, June 4

8:00 – 11:30 a.m. CDT

DARZALEX

Abstract #8002

Daratumumab (DARA) in combination with carfilzomib and dexamethasone (D-Kd) in lenalidomide (Len)-refractory patients (Pts) with relapsed multiple myeloma (MM): Subgroup analysis of MMY1001

Oral Presentation

Friday, June 1

3:09 – 3:21 p.m. CDT

Abstract #8013

Subcutaneous daratumumab (DARA) in patients (Pts) with relapsed or refractory multiple myeloma (RRMM): Part 2 update of the open-label, multicenter, dose escalation Phase 1b study (PAVO)

Poster Discussion

Monday, June 4

8:00 – 11:30 a.m. CDT

Abstract #8011

Subcutaneous daratumumab (DARA SC) plus cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in patients (Pts) with newly diagnosed amyloid light chain (AL) amyloidosis: Safety run-in results of ANDROMEDA

Poster Discussion

Monday, June 4

8:00 – 11:30 a.m. CDT

Abstract #8031

Daratumumab plus bortezomib-melphalan-prednisone (VMP) in elderly (≥75 y) patients (Pts) with newly diagnosed multiple myeloma (NDMM) ineligible for transplantation (ALCYONE)

Poster Session

Monday, June 4

8:00 – 11:30 a.m. CDT

Abstract #TPS8059

Pomalidomide and dexamethasone (pom-dex) with or without daratumumab (DARA) in patients (pts) with relapsed or refractory multiple myeloma (RRMM): a multicenter, randomized, Phase 3 study (APOLLO)

Poster Session

Monday, June 4

8:00 – 11:30 a.m. CDT

Abstract #TPS8058

Randomized, open-label, non-inferiority, Phase 3 study of subcutaneous (SC) versus intravenous (IV) daratumumab (DARA) administration in patients with relapsed or refractory multiple myeloma (RRMM): COLUMBA

Poster Session

Monday, June 4

8:00 – 11:30 a.m. CDT

Abstract #8042

Health-related quality of life in patients with newly diagnosed multiple myeloma who are ineligible for stem cell transplantation: Results from the ALCYONE trial

Poster Session

Monday, June 4

8:00 – 11:30 a.m. CDT

Abstract #TPS8062

Randomized, open-label, Phase 3 study of subcutaneous daratumumab (DARA SC) versus active monitoring in patients (Pts) with high-risk smoldering multiple myeloma (SMM): AQUILA

Poster Session

Monday, June 4

8:00 – 11:30 a.m. CDT

Abstract #TPS8057

Randomized, open-label, Phase 2/3 study of daratumumab (DARA) with or without JNJ-63723283, an anti-PD-1 monoclonal antibody, in relapsed/refractory multiple myeloma (RRMM)

Poster Session

Monday, June 4

8:00 – 11:30 a.m. CDT

ERLEADA

Abstract #5033

Relationship of time to metastasis (TTM) and site of metastases in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC): Results from the Phase 3 SPARTAN trial

Poster Discussion

Saturday, June 2

1:15 – 4:45 p.m. CDT

Abstract #5034

Predicting disease progression in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC): An analysis from the Phase 3 SPARTAN trial

Poster Discussion

Saturday, June 2

1:15 – 4:45 p.m. CDT

ZYTIGA

Abstract #5028

Subsequent treatment after abiraterone acetate + prednisone (AA + P) in patients (pts) with newly diagnosed high-risk metastatic castration-naïve prostate cancer (NDx-HR mCNPC): detailed analyses from the Phase 3 LATITUDE trial

Poster Discussion

Saturday, June 2

1:15 – 4:45 p.m. CDT

Abstract #5023

Longer term preplanned efficacy and safety analysis of abiraterone acetate + prednisone (AA + P) in patients (pts) with newly diagnosed high-risk metastatic castration-naïve prostate cancer (NDx-HR mCNPC) from the Phase 3 LATITUDE trial

Poster Discussion

Saturday, June 2

1:15 – 4:45 p.m. CDT

Abstract #5067

Clinical qualification of plasma androgen receptor (pAR) status and outcome on abiraterone acetate (AA) plus prednisone or dexamethasone (+P/D) in a Phase 2 multi-institutional study in metastatic castration resistant prostate cancer (mCRPC)

Poster Discussion

Saturday, June 2

1:15 – 4:45 p.m. CDT

Abstract #5038

A transcriptome analysis of castration resistant prostate cancer metastases in a prospective cohort study reveals high expression of AKT pathway genes predictive of long term response to abiraterone acetate/prednisone

Poster Discussion

Saturday, June 2

1:15 – 4:45 p.m. CDT

Prostate Cancer

Abstract #5032

Association of metastasis-free survival (MFS) and overall survival (OS) in nonmetastatic castration-resistant prostate cancer (nmCRPC)

Poster Discussion

Saturday, June 2

1:15 – 4:45 p.m. CDT

*Abstracts were submitted by IMBRUVICA co-developer partner, Pharmacyclics, an AbbVie company.

About Erdafitinib
Erdafitinib is a once-daily pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor being evaluated by Janssen Research and Development in Phase 2 and 3 clinical trials in patients with advanced urothelial cancer and other solid tumors.2 FGFRs are a family of receptor tyrosine kinases, which may be upregulated in various tumor cell types and may be involved in tumor cell proliferation, tumor angiogenesis and tumor cell survival.3 In 2008, Janssen entered into an exclusive worldwide license and collaboration agreement with Astex Therapeutics Ltd. to develop and commercialize erdafitinib.

About DARZALEX (daratumumab) Injection, for Intravenous Infusion
DARZALEX (daratumumab) injection for intravenous use is the first CD38-directed antibody approved anywhere in the world.4 CD38 is a surface protein that is highly expressed across multiple myeloma cells, regardless of disease stage.5 DARZALEX is believed to induce tumor cell death through multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), as well as through apoptosis, in which a series of molecular steps in a cell lead to its death.5 Subsets of myeloid derived suppressor cells (MDSCs), CD38+ regulatory T cells (Tregs) and CD38+ B cells (Bregs) were decreased by DARZALEX.4 DARZALEX is approved for use across multiple lines of therapy and is being evaluated in a comprehensive clinical development program across a range of treatment settings in multiple myeloma, such as in frontline and relapsed settings.6,7,8,9,10,11,12,13 Additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant hematologic diseases in which CD38 is expressed, such as smoldering myeloma, as well as in solid tumors.14,15,16 DARZALEX is the first and only CD38-directed antibody to receive regulatory approval to treat multiple myeloma.4

DARZALEX IMPORTANT SAFETY INFORMATION4

CONTRAINDICATIONS – None

WARNINGS AND PRECAUTIONS

Infusion Reactions – DARZALEX can cause severe infusion reactions. Approximately half of all patients experienced a reaction, most during the first infusion. Infusion reactions can also occur with subsequent infusions. Nearly all reactions occurred during infusion or within 4 hours of completing an infusion. Prior to the introduction of post-infusion medication in clinical trials, infusion reactions occurred up to 48 hours after infusion. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, laryngeal edema and pulmonary edema. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting and nausea. Less common symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, and hypotension.

Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt infusion for reactions of any severity and institute medical management as needed. Permanently discontinue therapy for life-threatening (Grade 4) reactions. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.

To reduce the risk of delayed infusion reactions, administer oral corticosteroids to all patients following DARZALEX infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease.

Interference with Serological Testing – Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive Indirect Antiglobulin Test (Indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type are not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX. Type and screen patients prior to starting DARZALEX.

Neutropenia – DARZALEX may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. DARZALEX dose delay may be required to allow recovery of neutrophils. No dose reduction of DARZALEX is recommended. Consider supportive care with growth factors.

Thrombocytopenia – DARZALEX may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. DARZALEX dose delay may be required to allow recovery of platelets. No dose reduction of DARZALEX is recommended. Consider supportive care with transfusions.

Interference with Determination of Complete Response – Daratumumab is a human IgG kappa monoclonal antibody that can be detected on both, the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.

Adverse Reactions – In patients who received DARZALEX in combination with bortezomib, melphalan, and prednisone, the most frequently reported adverse reactions (incidence ≥20%) were: upper respiratory tract infection (48%), infusion reactions (28%), and peripheral edema (21%). Serious adverse reactions (≥2% greater compared to the VMP arm) were pneumonia (11%), upper respiratory tract infection (5%), and pulmonary edema (2%). Treatment emergent grade 3-4 hematology laboratory abnormalities ≥20% were thrombocytopenia (38%), neutropenia (44%), and lymphopenia (58%).

In patients who received DARZALEX in combination with lenalidomide and dexamethasone, the most frequently reported adverse reactions (incidence ≥20%) were: neutropenia (92%), thrombocytopenia (73%), upper respiratory tract infection (65%), infusion reactions (48%), diarrhea (43%), fatigue (35%), cough (30%), muscle spasms (26%), nausea (24%), dyspnea (21%) and pyrexia (20%). The overall incidence of serious adverse reactions was 49%. Serious adverse reactions were pneumonia (12%), upper respiratory tract infection (7%), influenza (3%) and pyrexia (3%).

In patients who received DARZALEX in combination with bortezomib and dexamethasone, the most frequently reported adverse reactions (incidence ≥20%) were: thrombocytopenia (90%), neutropenia (58%), peripheral sensory neuropathy (47%), infusion reactions (45%), upper respiratory tract infection (44%), diarrhea (32%), cough (27%), peripheral edema (22%), and dyspnea (21%). The overall incidence of serious adverse reactions was 42%. Serious adverse reactions were upper respiratory tract infection (5%), diarrhea (2%) and atrial fibrillation (2%).

In patients who received DARZALEX as monotherapy, the most frequently reported adverse reactions (incidence ≥20%) were: neutropenia (60%), thrombocytopenia (48%), infusion reactions (48%), fatigue (39%), nausea (27%), back pain (23%), pyrexia (21%), cough (21%), and upper respiratory tract infection (20%). Serious adverse reactions were reported in 51 (33%) patients. The most frequent serious adverse reactions were pneumonia (6%), general physical health deterioration (3%), and pyrexia (3%).

In patients who received DARZALEX in combination with pomalidomide and dexamethasone, the most frequent adverse reactions (≥20%) were infusion reactions (50%), diarrhea (38%), constipation (33%), nausea (30%), vomiting (21%), fatigue (50%), pyrexia (25%), upper respiratory tract infection (50%), muscle spasms (26%), back pain (25%), arthralgia (22%), dizziness (21%), insomnia (23%), cough (43%) and dyspnea (33%). The overall incidence of serious adverse reactions was 49%. Serious adverse reactions reported in ≥5% patients included pneumonia (7%).

DRUG INTERACTIONS

Effect of Other Drugs on daratumumab: The coadministration of lenalidomide, pomalidomide or bortezomib with DARZALEX did not affect the pharmacokinetics of daratumumab.

Effect of Daratumumab on Other Drugs: The coadministration of DARZALEX with bortezomib or pomalidomide did not affect the pharmacokinetics of bortezomib.

About ERLEADA
ERLEADA (apalutamide) is an androgen receptor (AR) inhibitor indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer and was approved by the FDA on February 14, 2018 as the first approved treatment for this disease state.17

ERLEADA is a next-generation AR inhibitor that binds directly to the ligand-binding domain of the AR. ERLEADA inhibits AR nuclear translocation, inhibits DNA binding, and impedes AR-mediated transcription. A major metabolite, N-desmethyl apalutamide, is a less potent inhibitor of AR, and exhibited one-third the activity of ERLEADA in an in vitro transcriptional reporter assay. ERLEADA administration caused decreased tumor cell proliferation and increased apoptosis leading to decreased tumor volume in mouse xenograft models of prostate cancer.18

Full prescribing information is available at www.ERLEADA.com.

ERLEADA IMPORTANT SAFETY INFORMATION18

Do not take ERLEADA (apalutamide) if you:

are pregnant or may become pregnant. ERLEADA may harm your unborn baby.
are female. ERLEADA is not for use in women.
Before taking ERLEADA, tell your healthcare provider about all your medical conditions, including if you:

have a history of seizures, brain injury, stroke, or brain tumors.
have a partner who is pregnant or may become pregnant. Men who are sexually active with a pregnant woman must use a condom during and for 3 months after treatment with ERLEADA. If your sexual partner may become pregnant, an effective birth control (contraception) must be used during and for 3 months after treatment. Talk with your healthcare provider if you have questions about birth control.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. ERLEADA can interact with many other medicines.

You should not start or stop any medicine before you talk with the healthcare provider that prescribed ERLEADA.

Know the medicines you take. Keep a list of them with you to show to your healthcare provider and pharmacist when you get a new medicine.

How should I take ERLEADA?

Take ERLEADA exactly as your healthcare provider tells you.
Take your prescribed dose of ERLEADA 1 time a day, at the same time each day.
Take ERLEADA with or without food.
Swallow ERLEADA tablets whole.
Your healthcare provider may change your dose if needed.
Do not stop taking your prescribed dose of ERLEADA without talking with your healthcare provider first.
If you miss a dose of ERLEADA, take your normal dose as soon as possible on the same day. Return to your normal schedule on the following day. You should not take extra tablets to make up the missed dose.
You should start or continue a gonadotropin-releasing hormone (GnRH) analog therapy during your treatment with ERLEADA unless you had a surgery to lower the amount of testosterone in your body (surgical castration).
If you take too much ERLEADA, call your healthcare provider or go to the nearest hospital emergency room.
Your healthcare provider may do blood tests to check for side effects.

What are the possible side effects of ERLEADA?

ERLEADA may cause serious side effects including:

Falls and fractures. ERLEADA treatment can cause bones and muscles to weaken and may increase your risk for falls and fractures. Falls and fractures have happened in people during treatment with ERLEADA. Falls were not caused by loss of consciousness (fainting) or seizures. Your healthcare provider will monitor your risks for falls and fractures during treatment with ERLEADA.
Seizure. If you take ERLEADA, you may be at risk of having a seizure. You should avoid activities where a sudden loss of consciousness could cause serious harm to yourself or others. Tell your healthcare provider right away if you have a loss of consciousness or seizure. Your healthcare provider will stop ERLEADA if you have a seizure during treatment.
The most common side effects of ERLEADA include:

feeling very tired
high blood pressure
rash
diarrhea
nausea
decreased appetite
weight loss
joint pain
fall
hot flash
bone injury (fracture)
swollen hands, ankles, or feet
ERLEADA may cause fertility problems in males, which may affect the ability to father children. Talk to your healthcare provider if you have concerns about fertility. Do not donate sperm during treatment with ERLEADA and for 3 months after the last dose of ERLEADA.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of ERLEADA.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Please see the full Prescribing Information for ERLEADA.

INDICATION
What is ERLEADA?
ERLEADA is a prescription medicine used to treat prostate cancer that has not spread to other parts of the body and no longer responds to a medical or surgical treatment that lowers testosterone.
It is not known if ERLEADA is safe or effective in children.

About IMBRUVICA
IMBRUVICA (ibrutinib) was one of the first therapies to receive U.S. approval after having received the FDA’s Breakthrough Therapy Designation.19 IMBRUVICA works by blocking a specific protein called Bruton’s tyrosine kinase (BTK). The BTK protein transmits important signals that tell B cells to mature and produce antibodies and is needed by specific cancer cells to multiply and spread.20 IMBRUVICA targets and blocks BTK, inhibiting the survival and spread of cancer cells, and impacting signaling associated with other serious conditions. Worldwide, IMBRUVICA was used to treat more than 100,000 patients to date. For more information, visit www.IMBRUVICA.com.

Additional Information about IMBRUVICA
INDICATIONS
IMBRUVICA is indicated to treat adults with21

Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL)
Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) with 17p deletion
Waldenström’s macroglobulinemia (WM)
Mantle cell lymphoma (MCL) patients who have received at least one prior therapy
Accelerated approval was granted for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Marginal zone lymphoma (MZL) patients who require systemic therapy and have received at least one prior anti-CD20-based therapy
Accelerated approval was granted for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Chronic Graft-Versus-Host Disease (cGVHD) patients who failed one or more lines of systemic therapy
IMBRUVICA IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS

Hemorrhage: Fatal bleeding events have occurred in patients treated with IMBRUVICA. Grade 3 or higher bleeding events (intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post-procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA.

The mechanism for the bleeding events is not well understood.

IMBRUVICA may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding.

Consider the benefit-risk of withholding IMBRUVICA for at least 3 to 7 days pre and post-surgery depending upon the type of surgery and the risk of bleeding.

Infections: Fatal and non-fatal infections (including bacterial, viral, or fungal) have occurred with IMBRUVICA therapy. Grade 3 or greater infections occurred in 14% to 29% of patients. Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jiroveciipneumonia (PJP) have occurred in patients treated with IMBRUVICA. Consider prophylaxis according to standard of care in patients who are at increased risk for opportunistic infections.

Monitor and evaluate patients for fever and infections and treat appropriately.

Cytopenias: Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 13 to 29%), thrombocytopenia (range, 5 to 17%), and anemia (range, 0 to 13%) based on laboratory measurements occurred in patients with B-cell malignancies treated with single agent IMBRUVICA.

Monitor complete blood counts monthly.

Cardiac Arrhythmias: Fatal and serious cardiac arrhythmias have occurred with IMBRUVICA therapy. Grade 3 or greater ventricular tachyarrhythmias occurred in 0 to 1% of patients, and Grade 3 or greater atrial fibrillation and atrial flutter occurred in 0 to 6% of patients. These events have occurred particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of cardiac arrhythmias.

Periodically monitor patients clinically for cardiac arrhythmias. Obtain an ECG for patients who develop arrhythmic symptoms (e.g., palpitations, lightheadedness, syncope, chest pain) or new onset dyspnea. Manage cardiac arrhythmias appropriately, and if it persists, consider the risks and benefits of IMBRUVICA treatment and follow dose modification guidelines.

Hypertension: Hypertension (range, 6 to 17%) has occurred in patients treated with IMBRUVICA with a median time to onset of 4.6 months (range, 0.03 to 22 months). Monitor patients for new onset hypertension or hypertension that is not adequately controlled after starting IMBRUVICA.

Adjust existing anti-hypertensive medications and/or initiate anti-hypertensive treatment as appropriate.

Second Primary Malignancies: Other malignancies (range, 3 to 16%) including non-skin carcinomas (range, 1 to 4%) have occurred in patients treated with IMBRUVICA. The most frequent second primary malignancy was non-melanoma skin cancer (range, 2 to 13%).

Tumor Lysis Syndrome: Tumor lysis syndrome has been infrequently reported with IMBRUVICA therapy. Assess the baseline risk (e.g., high tumor burden) and take appropriate precautions.

Monitor patients closely and treat as appropriate.

Embryo-Fetal Toxicity: Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA and for 1 month after cessation of therapy. 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 a fetus. Advise men to avoid fathering a child during the same time period.

ADVERSE REACTIONS

B-cell malignancies: The most common adverse reactions (≥20%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were thrombocytopenia (62%)*, neutropenia (61%)*, diarrhea (43%), anemia (41%)*, musculoskeletal pain (30%), bruising (30%), rash (30%), fatigue (29%), nausea (29%), hemorrhage (22%), and pyrexia (21%).

The most common Grade 3 or 4 adverse reactions (≥5%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were neutropenia (39%)*, thrombocytopenia (16%)*, and pneumonia (10%).

Approximately 6% (CLL/SLL), 14% (MCL), 11% (WM) and 10% (MZL) of patients had a dose reduction due to adverse reactions. Approximately 4%-10% (CLL/SLL), 9% (MCL), and 9% (WM [6%] and MZL [13%]) of patients discontinued due to adverse reactions.

cGVHD: The most common adverse reactions (≥20%) in patients with cGVHD were fatigue (57%), bruising (40%), diarrhea (36%), thrombocytopenia (33%)*, stomatitis (29%), muscle spasms (29%), nausea (26%), hemorrhage (26%), anemia (24%)*, and pneumonia (21%).

The most common Grade 3 or 4 adverse reactions (≥5%) reported in patients with cGVHD were fatigue (12%), diarrhea (10%), neutropenia (10%)*, pneumonia (10%), sepsis (10%), hypokalemia (7%), headache (5%), musculoskeletal pain (5%), and pyrexia (5%).

Twenty-four percent of patients receiving IMBRUVICA in the cGVHD trial discontinued treatment due to adverse reactions. Adverse reactions leading to dose reduction occurred in 26% of patients.

*Treatment-emergent decreases (all grades) were based on laboratory measurements and adverse reactions.

DRUG INTERACTIONS

CYP3A Inhibitors: Dose adjustment may be recommended.

CYP3A Inducers: Avoid coadministration with strong CYP3A inducers.

SPECIFIC POPULATIONS

Hepatic Impairment (based on Child-Pugh criteria): Avoid use of IMBRUVICA in patients with severe baseline hepatic impairment. In patients with mild or moderate impairment, reduce IMBRUVICA dose.

Please see Full Prescribing Information: View Source

About ZYTIGA 22
ZYTIGA (abiraterone acetate) in combination with prednisone is indicated for the treatment of patients

with metastatic castration-resistant prostate cancer (CRPC)
with metastatic high-risk castration-sensitive prostate cancer (CSPC)
For more information about ZYTIGA, visit www.ZYTIGA.com.

ZYTIGA IMPORTANT SAFETY INFORMATION
Contraindications – ZYTIGA (abiraterone acetate) can cause fetal harm and potential loss of pregnancy.

Hypertension, Hypokalemia and Fluid Retention Due to Mineralocorticoid Excess – ZYTIGA may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition [see Clinical Pharmacology (12.1)]. Monitor patients for hypertension, hypokalemia, and fluid retention at least once a month. Control hypertension and correct hypokalemia before and during treatment.

Closely monitor patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalemia or fluid retention, such as those with heart failure, recent myocardial infarction, cardiovascular disease, or ventricular arrhythmia. The safety of ZYTIGA in patients with left ventricular ejection fraction <50% or New York Heart Association (NYHA) Class III or IV heart failure (in COU-AA-301) or NYHA Class II to IV heart failure (in COU-AA-302 and LATITUDE) has not been established because these patients were excluded from these randomized clinical trials [see Clinical Studies (14)].

Adrenocortical Insufficiency (AI) – AI was reported in patients receiving ZYTIGA in combination with prednisone, after an interruption of daily steroids and/or with concurrent infection or stress. Monitor patients for symptoms and signs of AI if prednisone is stopped or withdrawn, if prednisone dose is reduced, or if the patient experiences unusual stress. Symptoms and signs of AI may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with ZYTIGA. Perform appropriate tests, if indicated, to confirm AI. Increased dosages of corticosteroids may be used before, during, and after stressful situations.

Hepatotoxicity – In postmarketing experience, there have been ZYTIGA-associated severe hepatic toxicities, including fulminant hepatitis, acute liver failure and deaths. Measure serum transaminases alanine aminotransferase (ALT and AST) and bilirubin levels prior to starting treatment with ZYTIGA, every two weeks for the first three months of treatment, and monthly thereafter. In patients with baseline moderate hepatic impairment receiving a reduced ZYTIGA dose of 250 mg, measure ALT, AST, and bilirubin prior to the start of treatment, every week for the first month, every two weeks for the following two months of treatment and monthly thereafter. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop. Elevations of AST, ALT, or bilirubin from the patient’s baseline should prompt more frequent monitoring. If at any time AST or ALT rise above five times the upper limit of normal (ULN) or the bilirubin rises above three times the ULN, interrupt ZYTIGA treatment and closely monitor liver function. Re-treatment with ZYTIGA at a reduced dose level may take place only after return of liver function tests to the patient’s baseline or to AST and ALT less than or equal to 2.5X ULN and total bilirubin less than or equal to 1.5X ULN [See Dosage and Administration (2.4)].

Permanently discontinue ZYTIGA for patients who develop a concurrent elevation of ALT greater than 3X ULN and total bilirubin greater than 2X ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation.

The safety of ZYTIGA re-treatment of patients who develop AST or ALT greater than or equal to 20X ULN and/or bilirubin greater than or equal to 10X ULN is unknown.

Adverse Reactions – The most common adverse reactions (≥10%) are fatigue, arthralgia, hypertension, nausea, edema, hypokalemia, hot flush, diarrhea, vomiting, upper respiratory tract infection, cough, and headache.

The most common laboratory abnormalities (>20%) are anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia and hypokalemia.

Drug Interactions – Based on in vitro data, ZYTIGA is a substrate of CYP3A4. In a drug interaction trial, co-administration of rifampin, a strong CYP3A4 inducer, decreased exposure of abiraterone by 55%. Avoid concomitant strong CYP3A4 inducers during ZYTIGA treatment. If a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA dosing frequency only during the co-administration period [see Dosage and Administration (2.3)]. In a dedicated drug interaction trial, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone.
ZYTIGA is an inhibitor of the hepatic drug-metabolizing enzymes CYP2D6 and CYP2C8. Avoid co-administration with CYP2D6 substrates with a narrow therapeutic index. If alternative treatments cannot be used, consider a dose reduction of the CYP2D6 substrate drug. In a CYP2C8 drug interaction trial in healthy subjects, the AUC of pioglitazone, a CYP2C8 substrate, was increased by 46% when administered with a single dose of ZYTIGA. Patients should be monitored closely for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with ZYTIGA.

Use in Specific Populations

Females and Males of Reproductive Potential: Advise males with female partners of reproductive potential to use effective contraception.
Do not use ZYTIGA in patients with baseline severe hepatic impairment (Child-Pugh Class C

On May 16, 2018 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported follow-up data from the Phase III ALEX study, showing that as an initial treatment Alecensa (alectinib) significantly reduced the risk of disease progression or death (progression-free survival; PFS) by 57 percent (hazard ratio [HR]= 0.43, 95 percent CI: 0.32-0.58) compared to crizotinib after two years of follow-up in people with anaplastic lymphoma kinase (ALK)-positive metastatic (advanced) non-small cell lung cancer (NSCLC), as assessed by the investigator (Press release, Genentech, MAY 16, 2018, View Source [SID1234526760]). The median PFS for people who received Alecensa was more than tripled compared to those who received crizotinib (34.8 months [95 percent CI: 17.7 months-NE] versus 10.9 months [95 percent CI: 9.1-12.9]), respectively, as assessed by the investigator. The safety profile for Alecensa was consistent with that observed in previous studies.

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"Follow-up results from the ALEX study demonstrate the significant sustained benefit of Alecensa, showing that people with metastatic ALK-positive non-small cell lung cancer lived for almost three years without their disease progressing," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "These results further support the use of Alecensa as a standard of care for people who are newly diagnosed with this form of lung cancer."

The longer-term analysis also included follow-up data for secondary endpoints of the ALEX study. Alecensa demonstrated superior efficacy compared to crizotinib regardless of the presence of central nervous system (CNS) metastases at baseline. Investigator-assessed median PFS for people without CNS metastases at baseline was 34.8 months with Alecensa (95 percent CI: 22.4-NE) versus 14.7 months (95 percent CI: 10.8-20.3) with crizotinib (HR=0.47, 95 percent CI: 0.32-0.71). Investigator-assessed median PFS for people with CNS metastases at baseline was 27.7 months in the Alecensa arm (95 percent CI: 9.2-NE) versus 7.4 months (95 percent CI: 6.6-9.6) in the crizotinib arm (HR=0.35, 95 percent CI: 0.22-0.56). The duration of response (DOR) for people who received Alecensa was 33.3 months (95 percent CI: 31.3-NE) compared to 11.1 months (95 percent CI: 7.5-13.0 months) for people who received crizotinib.

The data will be presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on Sunday, June 3, 2018, at 8:00 – 11:30 a.m. CDT (Abstract #9043).

Alecensa is approved by the U.S. Food and Drug Administration (FDA) for the treatment of people with ALK-positive metastatic NSCLC as detected by an FDA-approved test.

About the ALEX study

ALEX (NCT02075840/B028984) is a randomized, multicenter, open-label Phase III study evaluating the efficacy and safety of Alecensa versus crizotinib in treatment-naïve people with ALK-positive NSCLC whose tumors were characterized as ALK-positive by the VENTANA ALK (D5F3) CDx Assay, a companion immunohistochemistry (IHC) test developed by Roche Tissue Diagnostics. People were randomized (1:1) to receive either Alecensa or crizotinib. The primary endpoint of the ALEX study was PFS as assessed by the investigator, and secondary endpoints include: Independent Review Committee (IRC)-assessed PFS, time to CNS progression, objective response rate (ORR), DOR and overall survival (OS). The multicenter study was conducted in 303 people across 161 sites in 31 countries. OS data are currently considered immature with only about a third of events being reported.

Primary data from the ALEX study were previously presented at the 2017 ASCO (Free ASCO Whitepaper) Annual Meeting and published in the New England Journal of Medicine. Follow-up results from the ALEX study analysis to be presented at the 2018 ASCO (Free ASCO Whitepaper) Annual Meeting showed:

After a further 10 months of follow-up, Alecensa reduced the risk of disease worsening or death (PFS) by 57 percent compared to crizotinib (HR=0.43, 95 percent CI: 0.32-0.58). Median follow-up was 27.8 months versus 22.8 months for Alecensa-treated patients and crizotinib-treated patients, respectively.
Investigator-reported median PFS (the primary endpoint) was 34.8 months in the Alecensa arm (95 percent CI: 17.7-NE) versus 10.9 months (95 percent CI: 9.1-12.9 months) in the crizotinib arm.
ORR for people treated with Alecensa was 82.9 percent (95 percent CI: 75.95-88.51) compared to 75.5 percent (95 percent CI: 67.84-82.12) for people treated with crizotinib, as assessed by the investigator.
Alecensa demonstrated superior efficacy compared to crizotinib regardless of the presence or absence of CNS metastases at baseline. Investigator-assessed median PFS for people without CNS metastases at baseline was 34.8 months with Alecensa (95 percent CI: 22.4-NE) versus 14.7 months (95 percent CI: 10.8-20.3) with crizotinib (HR=0.47, 95 percent CI: 0.32-0.71). Investigator-reported median PFS for people with CNS metastases at baseline was 27.7 months in the Alecensa arm (95 percent CI: 9.2-NE) versus 7.4 months (95 percent CI: 6.6-9.6) in the crizotinib arm (HR=0.35, 95 percent CI: 0.22-0.56).
Improvements were observed in the time between first response to treatment and disease worsening (DOR): 33.3 months with Alecensa versus 11.1 months with crizotinib.
Grade 3-5 adverse events (AEs) were less frequent in the Alecensa arm (44.7 percent) compared to the crizotinib arm (51.0 percent). The most common Grade 3-4 AEs were increased liver enzymes (aspartate transaminase; 5.5 percent, and alanine transaminase; 4.6 percent) and increased muscle enzymes (creatine phosphokinase; 3.3 percent). Serious adverse reactions reported in ≥ 2 percent of people treated with Alecensa were acute kidney injury (2.6 percent) and decreased red blood cells (anemia; 2.0 percent).
AEs leading to dose reduction (16.4 percent versus 20.5 percent) and dose interruption (22.4 percent versus 25.2 percent) were lower in the Alecensa arm compared with the crizotinib arm. AEs leading to discontinuation were equal in both arms (13.2 percent).
The FDA approval of Alecensa for the treatment of people with ALK-positive metastatic NSCLC was based on results from the Phase III ALEX study from the primary data cutoff in February 2017. Results showed that:

Alecensa significantly reduced the risk of disease worsening or death (PFS) by 47 percent (HR=0.53, 95 percent CI: 0.38, 0.73, p<0.0001) compared to crizotinib as assessed by an IRC.
The median PFS was 25.7 months (95 percent CI: 19.9, NE) for people who received Alecensa compared with 10.4 months (95 percent CI: 7.7-14.6) for people who received crizotinib as assessed by an IRC.
Alecensa significantly reduced the risk of the cancer spreading to or growing in the brain or CNS compared to crizotinib by 84 percent (HR=0.16, 95 percent CI: 0.10, 0.28, p<0.0001). This was based on a time to CNS progression analysis in which there was a lower risk of progression in the CNS as the first site of disease progression for people who received Alecensa (12 percent) compared to people who received crizotinib (45 percent).
The safety profile of Alecensa was consistent with that observed in previous studies.
Grade ≥ 3 adverse reactions were reported for 41 percent of people treated with Alecensa. The most common Grade 3-4 adverse reactions (≥ 3 percent) were evidence of kidney dysfunction (increased creatinine; 4.1 percent), evidence of liver dysfunction (hyperbilirubinemia; 5 percent), low levels of sodium (hyponatremia; 6 percent), increased liver enzymes (aspartate transaminase; 6 percent, and alanine transaminase; 6 percent), and decreased red blood cells (anemia; 7 percent). Serious adverse reactions reported in ≥ 2 percent of people treated with Alecensa were pneumonia (4.6 percent) and renal impairment (3.9 percent).
About lung cancer

According to the American Cancer Society, it is estimated that more than 234,000 Americans will be diagnosed with lung cancer in 2018, and NSCLC accounts for 85 percent of all lung cancers. It is estimated that approximately 60 percent of lung cancer diagnoses in the United States are made when the disease is in the advanced stages.

About Alecensa (alectinib)

Alecensa is a kinase inhibitor approved for the treatment of people with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.

Alecensa U.S. Indication

Alecensa is a kinase inhibitor approved for the treatment of people with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.

Important Safety Information

Everyone reacts differently to treatment with Alecensa. It’s important to know the most serious and most common side effects with Alecensa.

A doctor may lower the dose or stop treatment with Alecensa if any serious side effects occur. Patients taking Alecensa should contact their doctor right away if they have any of the following side effects.

Alecensa may cause serious side effects, including:

Liver problems (hepatotoxicity). Alecensa may cause liver injury. A doctor will do blood tests at least every 2 weeks for the first 3 months and as needed during treatment with Alecensa. Patients taking Alecensa should tell their doctor right away if they experience any of the following signs and symptoms:

Feeling tired
Feeling less hungry than usual
Yellowing of the skin or whites of the eyes
Dark urine
Itchy skin
Nausea or vomiting
Pain on the right side of stomach area
Bleeding or bruising more easily than normal
Lung problems. Alecensa may cause severe or life-threatening swelling (inflammation) of the lungs during treatment. Symptoms may be similar to those symptoms from lung cancer. Patients taking Alecensa should tell their doctor right away if they have any new or worsening symptoms, including:

Trouble breathing
Shortness of breath
Fever
Cough
Kidney problems. Alecensa may cause severe or life-threatening kidney problems. Tell your healthcare provider right away if you have a change in the amount or color of your urine, or if you get new or worsening swelling in your legs or feet.

Slow heartbeat (bradycardia). Alecensa may cause very slow heartbeats that can be severe. A doctor will check a patient’s heart rate and blood pressure during treatment with Alecensa. Patients taking Alecensa should tell their doctor right away if they feel dizzy, lightheaded, or faint during treatment with Alecensa. Patients taking Alecensa should tell their doctor if they take any heart or blood pressure medicines.

Muscle pain, tenderness, and weakness (myalgia). Muscle problems are common with Alecensa and can be severe. A doctor will do blood tests at least every 2 weeks for the first month and as needed during treatment with Alecensa. Patients taking Alecensa should tell their doctor right away if they have any new or worsening signs and symptoms of muscle problems, including unexplained muscle pain or muscle pain that does not go away, tenderness, or weakness.

Before taking Alecensa, patients should tell their doctor about all medical conditions, including if they:

Have liver problems
Have lung or breathing problems
Have a slow heartbeat
Are pregnant or plan to become pregnant. Alecensa can harm an unborn baby. Patients taking Alecensa should tell their doctor right away if they become pregnant during treatment with Alecensa or think they may be pregnant
Women who are able to become pregnant should use effective birth control during treatment with Alecensa and for one week after the final dose of Alecensa
Men who have female partners that are able to become pregnant should use effective birth control during treatment with Alecensa and for three months after the final dose of Alecensa
Are breastfeeding or plan to breastfeed. It is not known if Alecensa passes into breast milk. A patient should not breastfeed during treatment with Alecensa and for one week after the final dose of Alecensa. Patients should talk with their doctor about the best way to feed their baby during this time.
Patients taking Alecensa should tell their doctor about all the medicines they take, including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements.

Patients taking Alecensa should avoid spending time in the sunlight during treatment with Alecensa and for seven days after the final dose of Alecensa. Patients taking Alecensa may burn more easily and get severe sunburns. Patients taking Alecensa should use sunscreen and lip balm with a SPF 50 or greater to help protect against sunburn.

The most common side effects of Alecensa include:

Tiredness
Constipation
Swelling in hands, feet, ankles, and eyelids
Low red blood cell count
These are not all of the possible side effects of Alecensa. For more information, patients should ask their doctor or pharmacist. Patients should call their doctor for medical advice about side effects.

Report side effects to the FDA at (800) FDA-1088 or View Source Patients and caregivers may also report side effects to Genentech at (888) 835-2555.