On May 17, 2017 Incyte Corporation (Nasdaq:INCY) reported the publication of new data from the ongoing ECHO-202 trial, evaluating epacadostat, Incyte’s selective IDO1 enzyme inhibitor, in combination with Keytruda (pembrolizumab), Merck’s anti-PD-1 therapy (Press release, Incyte, MAY 17, 2017, View Source [SID1234519189]).

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Abstracts published online by the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in advance of its annual meeting in Chicago, Illinois, June 2-6, 2017 include ECHO-202 Phase 1/2 efficacy and safety data from the following cohorts: non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), bladder cancer, squamous cell carcinoma of the head and neck (SCCHN), triple-negative breast cancer (TNBC), and ovarian cancer (OVC). Pooled Phase 2 safety data across cohorts were also released today.

"We are very pleased to share these new data for epacadostat in combination with pembrolizumab. The combination is well-tolerated and preliminary efficacy outcomes for these cohorts demonstrate encouraging clinical activity, both within and across tumor types, which compares favorably to contemporary data in the second-line setting. These data, including updated data which will be presented at ASCO (Free ASCO Whitepaper) next month, supported the recently-announced progression of the epacadostat and pembrolizumab combination into pivotal trials in NSCLC, RCC, bladder cancer and SCCHN," said Steven Stein, M.D., Chief Medical Officer, Incyte.

ECHO-202 abstract data for the tumor types entering Phase 3 (data cut as of October 29, 2016) include:

n/N
(%)
NSCLC UC SCCHN RCC
All pts
0-2 prior lines of
therapy for advanced
disease
All pts
Prior Lines of
Treatment
All pts
Prior Lines of
Treatment
All pts
Prior Lines of
Treatment
Total TPS ≥50% TPS <50% Total 0-1 Total 1-2 ≥3 Total 0-1 ≥2
ORR 14/40
(35) 3/7
(43) 6/17
(35) 13/37
(35) 10/27
(37)
11/36
(31)

10/29
(34)

1/7
(14)

9/30
(30)

9/19
(47)
0/11
(0)
all PR all PR all PR all PR all PR 2 CR,
9 PR 2 CR,
8 PR 1 PR 1 CR,
8 PR 1 CR,
8 PR -
DCR 24/40
(60) 4/7
(57) 9/17
(53) 21/37
(57) 17/27
(63) 21/36
(58)
18/29
(62)
3/7
(43) 15/30
(50) 11/19
(58) 4/11
(36)

DoR
12/14 responses ongoing
range 1+ – 519 days

12/13 responses ongoing
range 1+ – 652+ days

9/11 responses ongoing
range 1+ – 563+ days

9/9 responses ongoing
range 1+ – 372+ days

In a pooled analysis evaluating 244 patients in the ECHO-202 Phase 2 safety population (abstract #3012), treatment-related adverse events (TRAEs) that occurred in ≥5 percent of patients, included fatigue (23 percent); rash (16 percent); diarrhea and nausea (7 percent each); increased alanine aminotransferase, increased aspartate aminotransferase, and pruritus (6 percent each); and pyrexia (5 percent). A total of 37 patients (15 percent) experienced Grade ≥3 TRAEs; the most common of which were increased lipase (asymptomatic) and rash (3 percent each). TRAEs led to discontinuation of treatment in 3 percent of study patients.
These abstracts, including data for TNBC and OVC (abstract #1103), were made available today on the ASCO (Free ASCO Whitepaper) website at www.asco.org.

About ECHO-202 (KEYNOTE-037)
The ECHO-202 study (NCT02178722) is evaluating the safety and efficacy of epacadostat, Incyte’s selective IDO1 inhibitor, in combination with pembrolizumab. Patients previously treated with anti-PD-1 or anti-CTLA-4 therapies were excluded from this trial. Enrollment is complete for the Phase 1 dose escalation (epacadostat 25, 50, 100 mg BID + pembrolizumab 2 mg/kg IV Q3W and epacadostat 300 mg BID + pembrolizumab 200 mg IV Q3W) and Phase 1 dose expansion (epacadostat 50, 100, and 300 mg BID + pembrolizumab 200 mg IV Q3W) portions of the trial. For more information about ECHO-202, visit View Source

About ECHO
The ECHO clinical trial program was established to investigate the efficacy and safety of epacadostat as a core component of combination therapy in oncology. Ongoing Phase 1 and Phase 2 studies evaluating epacadostat in combination with PD-1 and PD-L1 inhibitors collectively plan to enroll over 900 patients in a broad range of solid tumor types as well as hematological malignancies. ECHO-301 (NCT02752074), a Phase 3 randomized, double-blind, placebo-controlled study investigating KEYTRUDA in combination with epacadostat or placebo for the treatment of patients with unresectable or metastatic melanoma, is also underway. For more information about the ECHO clinical trial program, visit www.ECHOClinicalTrials.com.

About Epacadostat (INCB024360)
Indoleamine 2,3-dioxygenase 1 (IDO1) is a key immunosuppressive enzyme that modulates the anti-tumor immune response by promoting regulatory T cell generation and blocking effector T cell activation, thereby facilitating tumor growth by allowing cancer cells to avoid immune surveillance. Epacadostat is a first-in-class, highly potent and selective oral inhibitor of the IDO1 enzyme that regulates the tumor immune microenvironment, thereby restoring effective anti-tumor immune responses. In single-arm studies, the combination of epacadostat and immune checkpoint inhibitors has shown proof-of-concept in patients with unresectable or metastatic melanoma. In these studies, epacadostat combined with the CTLA-4 inhibitor ipilimumab or the PD-1 inhibitor pembrolizumab improved response rates compared with studies of the immune checkpoint inhibitors alone.

On May 17, 2017 Incyte Corporation (Nasdaq:INCY) reported that the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) has published Phase 1/2 data from the ongoing ECHO-204 trial evaluating the safety and efficacy of epacadostat, Incyte’s selective IDO1 enzyme inhibitor, in combination with Opdivo (nivolumab), Bristol-Myers Squibb’s PD-1 immune checkpoint inhibitor. Efficacy data in patients with squamous cell carcinoma of the head and neck (SCCHN), melanoma (MEL), ovarian cancer (OVC), and colorectal cancer (CRC), as well as overall safety data will be highlighted in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting in Chicago, Illinois from June 2-6, 2017.

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"These first Phase 1/2 data from our ECHO-204 trial evaluating epacadostat plus nivolumab in multiple solid tumors add to our knowledge of the therapeutic potential of IDO1 enzyme inhibition when combined with PD-1 blockade," said Steven Stein, M.D., Chief Medical Officer, Incyte. "These results show that the combination was well-tolerated across patients studied and demonstrates promising clinical responses, particularly in melanoma and SCCHN. We look forward to sharing updated data from these cohorts at ASCO (Free ASCO Whitepaper) next month, and to progressing our clinical development program for this combination into pivotal studies."

ECHO-204 Abstract Highlights

ECHO-204 evaluated the safety and efficacy of the epacadostat and nivolumab combination in 241 patients (data cut-off as of October 29, 2016). In 30 patients with MEL treated with nivolumab plus epacadostat at 100 mg or 300 mg, the combined disease control rate (DCR; defined as complete response + partial response + stable disease) was 73 percent (22/30). In patients with SCCHN treated with nivolumab plus epacadostat 300 mg, the preliminary DCR was 70 percent (16/23). Response rates based on updated data will be presented at the ASCO (Free ASCO Whitepaper) Annual Meeting.

In Phase 1 (dose escalation), 36 patients were enrolled and no dose-limiting toxicities were observed. Among the 205 patients enrolled in Phase 2, the most frequent treatment-related adverse events (TRAEs) (≥15 percent) in patients receiving epacadostat 100 mg BID (70/205) and 300 mg BID (135/205) were rash (33 percent and 22 percent, receptively), fatigue (26 percent and 31 percent), and nausea (24 percent and 19 percent). Rash was the most common ≥3 TRAE (10 percent and 12 percent). TRAEs led to discontinuation in 7 percent (100 mg) and 13 percent (300 mg) of patients. There were no treatment-related deaths.

This ECHO-204 abstract (#3003) was made available today on the ASCO (Free ASCO Whitepaper) website at www.asco.org.

About ECHO-204

The ECHO-204 study (NCT02327078) is a Phase 1/2 study evaluating the safety and efficacy of epacadostat, Incyte’s selective IDO1 inhibitor, in combination with nivolumab in subjects with select advanced solid tumors and lymphomas, including melanoma (MEL), non-small cell lung cancer (NSCLC), colorectal cancer (CRC), head and neck squamous cell carcinoma (SCCHN), ovarian cancer, and B cell non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL). Patients previously treated with anti-PD-1 or anti-CTLA-4 therapies were excluded from this trial. Enrollment for the Phase 2 (epacadostat 100 or 300 mg BID + nivolumab 240 Q2W) tumor-specific cohorts is ongoing. For more information about ECHO-204, visit View Source

About ECHO

The ECHO clinical trial program was established to investigate the efficacy and safety of epacadostat as a core component of combination therapy in oncology. Ongoing Phase 1 and Phase 2 studies evaluating epacadostat in combination with PD-1 and PD-L1 inhibitors collectively plan to enroll over 900 patients in a broad range of solid tumor types as well as hematological malignancies. For more information about the ECHO clinical trial program, visit www.ECHOClinicalTrials.com.

About Epacadostat (INCB024360)

Indoleamine 2,3-dioxygenase 1 (IDO1) is a key immunosuppressive enzyme that modulates the anti-tumor immune response by promoting regulatory T cell generation and blocking effector T cell activation, thereby facilitating tumor growth by allowing cancer cells to avoid immune surveillance. Epacadostat is a first-in-class, highly potent and selective oral inhibitor of the IDO1 enzyme that regulates the tumor immune microenvironment, thereby restoring effective anti-tumor immune responses. In single-arm studies, the combination of epacadostat and immune checkpoint inhibitors has shown proof-of-concept in patients with unresectable or metastatic melanoma. In these studies, epacadostat combined with the CTLA-4 inhibitor ipilimumab or the PD-1 inhibitor pembrolizumab improved response rates compared with studies of the immune checkpoint inhibitors alone.

On May 17, 2017 Eli Lilly and Company (NYSE: LLY) reported that new research demonstrating advances in the Company’s oncology pipeline and product portfolio will be presented at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago, June 2-6, 2017 (Press release, Eli Lilly, MAY 17, 2017, View Source [SID1234519185]). Data underscore a strategic focus on targeting the biology of cancer to find new ways to fight cancer and transform care for patients. Highlights include oral presentation of Phase 3 data for abemaciclib, an investigational cyclin-dependent kinase (CDK)4 & 6 inhibitor for breast cancer, as well as new data from the Company’s ongoing immuno-oncology clinical collaborations with Merck (known as MSD outside the U.S. and Canada) in two trials that are evaluating pemetrexed-plus-carboplatin and ramucirumab, respectively, in combination with Merck’s pembrolizumab.

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"We are pleased to share how we are building foundational therapeutics with the goal of delivering medicines that help people with cancer live longer and healthier lives," said Levi Garraway, M.D., Ph.D., senior vice president, global development and medical affairs, Lilly Oncology. "We are particularly excited about the latest results from the abemaciclib MONARCH clinical development program, in which we have endeavored to raise the bar with a potential next-generation CDK4 & 6 inhibitor that we believe may improve outcomes for patients living with breast cancer."

"With abemaciclib we hoped to develop an oral CDK4 & 6 inhibitor that could be taken without interruption. In preclinical research, continued disruption was shown to stop tumor cells from entering the cell cycle, which prevents tumor cell growth and, ultimately, promotes tumor cell death that may translate into clinical benefit for breast cancer patients," said Alfonso de Dios, senior research fellow, discovery chemistry research & technologies, Lilly.

Abemaciclib Data at ASCO (Free ASCO Whitepaper)
Detailed data from the Phase 3 MONARCH 2 study, which evaluated abemaciclib in combination with fulvestrant in women with hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer, will be presented in an oral presentation. The intent-to-treat population of 669 patients in MONARCH 2 had experienced disease progression on or within 12 months of receiving endocrine treatment in the neoadjuvant or adjuvant setting or while receiving first-line endocrine therapy for metastatic disease.

Additionally, abemaciclib has been shown in preclinical and Phase 1 studies to cross the blood-brain barrier, making this an area of interest for further study. This year’s meeting will allow Lilly to share preliminary Phase 2 data evaluating a CDK4 & 6 inhibitor in patients with new or progressive brain metastases secondary to advanced breast cancer, lung cancer or melanoma.

Select studies, along with the times and locations of their data sessions, are highlighted below.

Abemaciclib

Abstract #1000: Oral Presentation: Breast Cancer—Metastatic: Saturday, June 3, 2017; 1:15-4:15 p.m. CDT
MONARCH 2: Abemaciclib in combination with fulvestrant in patients with HR+/HER2- advanced breast cancer who progressed on endocrine therapy
Author/Speaker: George W. Sledge, M.D., F.A.S.C.O., Stanford University School of Medicine
Location: Hall D1
Abstract #1019: Breast Cancer—Metastatic: Sunday, June 4, 2017; 8:00-11:30 a.m. CDT
Abemaciclib for the treatment of brain metastases (BM) secondary to hormone-receptor-positive (HR+), HER2- breast cancer
Author/Speaker: Sara M. Tolaney, M.D., M.P.H., Dana-Farber Cancer Institute
Location: Hall A (Poster Board #11)
Poster Discussion Session: Sunday, June 4, 2017; 4:45-6:00 p.m. CDT, Hall B1
Abstract #TPS1109: Breast Cancer—Metastatic: Sunday, June 4, 2017; 8:00-11:30 a.m. CDT
A Phase 2 randomized study to compare abemaciclib plus trastuzumab with or without fulvestrant to standard of care chemotherapy plus trastuzumab in hormone-receptor-positive, HER2-positive, advanced breast cancer (monarcHER)
Author/Speaker: Sara M. Tolaney, M.D., M.P.H., Dana-Farber Cancer Institute
Location: Hall A (Poster Board #99b)
Abstract #TPS4150: Gastrointestinal (Noncolorectal) Cancer: Saturday, June 3, 2017; 8:00-11:30 a.m. CDT
A Phase 2 study of abemaciclib as a monotherapy and in combination with other agents in patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC)
Author/Speaker: E. Gabriela Chiorean, M.D., Fred Hutchinson Cancer Research Center
Location: Hall A (Poster Board #132b)
Fruquintinib

Abstract #3508: Oral Presentation: Gastrointestinal (Colorectal) Cancer: Monday, June 5, 2017; 3:00-6:00 p.m. CDT
A randomized, double-blind, placebo-controlled, multi-centered Phase 3 trial comparing fruquintinib versus placebo plus best supportive care in Chinese patients with metastatic colorectal cancer (FRESCO)
Author/Speaker: Jin Li, M.D., Fudan University Shanghai Cancer Center, Shanghai Medical College
Location: Hall D2
Immuno-Oncology Collaborations with pemetrexed-plus-carboplatin or ramucirumab

Abstract #9094: Lung Cancer—Non-Small Cell Metastatic: Saturday, June 3, 2017; 8:00-11:30 a.m. CDT
First-line carboplatin and pemetrexed (CP) with or without pembrolizumab (pembro) for advanced nonsquamous NSCLC: Updated results of KEYNOTE-021 cohort G
Author/Speaker: Vassiliki Papadimitrakopoulou, M.D., The University of Texas MD Anderson Cancer Center
Location: Hall A (Poster Board #420)
Abstract #4046: Gastrointestinal (Noncolorectal) Cancer: Saturday, June 3, 2017; 8:00-11:30 a.m. CDT
Ramucirumab (R) plus pembrolizumab (P) in treatment naive and previously treated advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: A multi-disease Phase 1 study
Author/Speaker: Ian Chau, M.D., F.R.C.P, Royal Marsden Hospital
Location: Hall A (Poster Board #38)
Olaratumab

Abstract #TPS2599: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics: Monday, June 5, 2017; 8:00-11:30 a.m. CDT
A Phase 1, open-label, dose-escalation study of olaratumab as a single agent and in combination with doxorubicin, vincristine/irinotecan, or high-dose ifosfamide in pediatric patients with relapsed or refractory solid tumors
Author/Speaker: Leo Mascarenhas, M.B.B.S., M.D., M.S., Children’s Center for Cancer and Blood Diseases, Children’s Hospital Los Angeles, University of Southern California
Location: Hall A (Poster Board #89b)
Emibetuzumab

Abstract #9019: Lung Cancer—Non-Small Cell Metastatic: Saturday, June 3, 2017; 8:00-11:30 a.m. CDT
A randomized, controlled, open-label Phase 2 study of erlotinib (E) with or without the MET antibody emibetuzumab (Emi) as first-line treatment for EFGRmt non-small cell lung cancer (NSCLC) patients who have disease control after an eight-week lead-in treatment with erlotinib
Author/Speaker: Giorgio V. Scagliotti, M.D., Ph.D., Department of Oncology – University of Torino
Location: Hall A (Poster Board #345)
Poster Discussion Session: Saturday, June 3, 2017; 3:00-4:15 p.m. CDT, Hall D2
Galunisertib

Abstract #4097: Gastrointestinal (Noncolorectal) Cancer: Saturday, June 3, 2017; 8:00-11:30 a.m. CDT
A Phase 2 study of galunisertib (TGF-B R1 inhibitor) and sorafenib in patients with advanced hepatocellular carcinoma (HCC)
Author/Speaker: Robin Kate Kelley, M.D., University of California, San Francisco
Location: Hall A (Poster Board #89)
LY3023414

Abstract #1064: Breast Cancer—Metastatic: Sunday, June 4, 2017; 8:00-11:30 a.m. CDT
Safety and tolerability of the dual PI3K/mTOR inhibitor LY3023414 in combination with fulvestrant in treatment refractory advanced breast cancer patients
Author/Speaker: Anna M. Varghese, M.D., Memorial Sloan-Kettering Cancer Center
Location: Hall A (Poster Board #56)
LY3009120

Abstract #2507: Oral Presentation: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics: Saturday, June 3, 2017; 1:15-4:15 p.m. CDT
A first-in-human dose Phase 1 study of LY3009120 in advanced cancer patients
Author/Speaker: David S. Hong, M.D., The University of Texas MD Anderson Cancer Center
Location: E450ab
LY3022855

Abstract #2523: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics: Monday, June 5, 2017; 8:00-11:30 a.m. CDT
A Phase 1 study of LY3022855, a colony-stimulating factor-1 receptor (CSF-1R) inhibitor, in patients (pts) with advanced solid tumors
Author/Speaker: Afshin Dowlati, M.D., University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University
Location: Hall A (Poster Board #15)
LY3039478

Abstract #6024: Head and Neck Cancer: Monday, June 5, 2017; 1:15-4:45 p.m. CDT
Notch pathway inhibition with LY3039478 in adenoid cystic carcinoma (ACC)
Author/Speaker: Caroline Even, Institut Gustave Roussy
Location: Hall A (Poster Board #12)
Poster Discussion Session: Monday, June 5, 2017; 4:45-6:00 p.m. CDT, S406

On May 17, 2017 Celldex Therapeutics, Inc. (Nasdaq:CLDX) reported that clinical results from the single-agent cohort of the Phase 2 study of glembatumumab vedotin in patients with metastatic melanoma and the Phase 1 dose-escalation study of varlilumab and nivolumab in multiple solid tumors, will be presented in oral presentations at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held June 2-6, 2017 in Chicago (Press release, Celldex Therapeutics, MAY 17, 2017, View Source [SID1234519184]). Information in the abstracts is current as of the time of submission in February 2017.

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Abstract #109: "A Phase 2 study of glembatumumab vedotin, an antibody-drug conjugate (ADC) targeting gpNMB, in advanced melanoma." Patrick A. Ott, M.D., Ph.D., Clinical Director of Dana-Farber Cancer Institute’s Melanoma Center and its Center for Immuno-Oncology, and Assistant Professor of Medicine at Harvard Medical School, will present results during the Clinical Science Symposium "Hitting the Target: Antibody-Drug Conjugates," which begins on Monday, June 5, 2017 at 9:45 a.m. CDT.
Abstract #3007: "Clinical results with combination of anti-CD27 agonist antibody, varlilumab, with anti-PD1 antibody nivolumab in advanced cancer patients." Rachel E. Sanborn, M.D., co-director of the Providence Thoracic Oncology Program at Providence Cancer Center in Portland, Ore., will present results during the session "Developmental Therapeutics—Immunotherapy," which begins on Monday, June 5, 2017 at 1:15 p.m. CDT.

On May 17, 2017 Amgen (NASDAQ:AMGN) reported that new clinical data and analyses from across its oncology portfolio will be presented at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago, June 2-6, 2017 (Press release, Amgen, MAY 17, 2017, View Source [SID1234519183]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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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"At Amgen, we are committed to translating science into innovative and effective treatments for cancer patients across the disease continuum," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "The data that will be presented at this year’s ASCO (Free ASCO Whitepaper) meeting highlight the potential of our marketed products in new patient populations and in combination with other therapies."

Amgen data to be presented at ASCO (Free ASCO Whitepaper) include an oral presentation of results from the Phase 3 ‘482 study, evaluating the efficacy and safety of XGEVA (denosumab) in a head-to-head comparison with zoledronic acid for the prevention of fractures and other bone complications in patients with newly diagnosed multiple myeloma. This abstract was also selected for inclusion in the Best of ASCO (Free ASCO Whitepaper) educational program, designed to increase global access to cutting-edge science. Current treatment options for bone complications are limited to bisphosphonates, which are associated with renal toxicity.

Impact of Denosumab (DMB) Compared With Zoledronic Acid (ZA) on Renal Function in the Treatment of Myeloma Bone Disease
Abstract #8005, Oral Presentation, Sunday, June 4 at 9:45 a.m. CT in McCormick Place, 354b

New IMLYGIC (talimogene laherparepvec) data will be presented, including the primary analysis of a Phase 2 study evaluating IMLYGIC in combination with an immune checkpoint inhibitor:

Primary Results From a Randomized (1:1), Open-Label Phase 2 Study of Talimogene Laherparepvec (T) and Ipilimumab (I) Versus I Alone in Unresected Stage IIIB- IV Melanoma
Abstract #9509, Poster Discussion, Saturday, June 3 at 4:45 p.m. CT in McCormick Place, 354b
Humanistic Burden of Disease in Earlier Stage Metastatic (Stage IIIB/C-IVM1A) Versus Late Stage Metastatic (IVM1B/C) Melanoma Patients in a Real World Setting in the US
Abstract #9561, Poster Presentation, Saturday, June 3 at 1:15 p.m. CT in McCormick Place, Hall A
Two abstracts will be presented on BLINCYTO (blinatumomab), the first-and-only approved CD19-directed CD3 bispecific T cell engager (BiTE) immunotherapy:

Blinatumomab Use in Pediatric Patients (Pts) With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (R/R ALL) From an Open-label, Multicenter, Expanded Access Study
Abstract #10530, Poster Presentation, Sunday, June 4 at 8 a.m. CT in McCormick Place, Hall A
Exposure-adjusted Adverse Events (AEs) Comparing Blinatumomab to Standard of Care (SOC) Chemotherapy in Patients (Pts) With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (R/R ALL) From a Randomized Phase III Study
Abstract #7032, Poster Presentation, Monday, June 5 at 8 a.m. CT in McCormick Place, Hall A
KYPROLIS (carfilzomib) is the first and only multiple myeloma therapy to demonstrate superior overall survival, reducing the risk of death by 21 percent, in a head-to-head comparison with Velcade (bortezomib) when each was added to dexamethasone in the relapsed setting.1 The KYPROLIS clinical development program is focused on providing solutions for physicians and patients in treating multiple myeloma. Data at ASCO (Free ASCO Whitepaper) include:

Rates of Peripheral Neuropathy (PN) in Patients (Pts) With Relapsed and Refractory Multiple Myeloma (RRMM) Treated With Carfilzomib vs Comparators in Pivotal Phase 3 Trials
Abstract #8041, Poster Presentation, Monday, June 5 at 8 a.m. CT in McCormick Place, Hall A
Presentations featuring Vectibix (panitumumab) data will include:

Profiling Circulating Tumor DNA (ctDNA) Mutations After Panitumumab Treatment in Patients With Refractory Metastatic Colorectal Cancer (mCRC) From the Phase III ASPECCT Study
Abstract #3523, Poster Discussion, Saturday, June 3 at 1:15 p.m. CT in McCormick Place, Arie Crown Theater
Early Tumor Shrinkage (ETS) and Depth of Response (DpR) in Wild-Type (WT) RAS Tumors from the Phase III Trial of Panitumumab (Pmab) Plus Best Supportive Care (BSC) Versus BSC in Chemorefractory Metastatic Colorectal Cancer (mCRC)
Abstract #3561, Poster Presentation, Saturday, June 3 at 8 a.m. CT in McCormick Place, Hall A
Clinical Outcomes and Emergent Circulating Tumor (Ct) DNA RAS Mutations and Allele Fraction for Patients With Metastatic Colorectal Cancer (mCRC) Treated With Panitumumab from the ASPECCT Study
Abstract #3584, Poster Presentation, Saturday, June 3 at 8 a.m. CT in McCormick Place, Hall A
Data will be presented on the investigational agent ABP 215, which is being developed as a bevacizumab biosimilar:

Clinical Comparison of ABP 215 and Bevacizumab in Patients With NSCLC: Pharmacokinetic Results and Justification for Extrapolation Across Bevacizumab Indications
Abstract #9050, Poster Presentation, Saturday, June 3 at 8 a.m. CT in McCormick Place, Hall A
Abstracts are currently available on the ASCO (Free ASCO Whitepaper) website.

About XGEVA (denosumab)
XGEVA targets the RANK Ligand pathway to prevent the formation, function and survival of osteoclasts, which break down bone. XGEVA is indicated for the prevention of SREs in patients with bone metastases from solid tumors and for treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity. XGEVA is also indicated in the U.S. for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy. XGEVA is not indicated for the prevention of SREs in patients with multiple myeloma.

U.S. Important Safety Information

Hypocalcemia
Pre-existing hypocalcemia must be corrected prior to initiating therapy with XGEVA. XGEVA can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Monitor calcium levels, especially in the first weeks of initiating therapy, and administer calcium, magnesium, and vitamin D as necessary. Monitor levels more frequently when XGEVA is administered with other drugs that can also lower calcium levels. Advise patients to contact a healthcare professional for symptoms of hypocalcemia.

An increased risk of hypocalcemia has been observed in clinical trials of patients with increasing renal dysfunction, most commonly with severe dysfunction (creatinine clearance less than 30 mL/minute and/or on dialysis), and with inadequate/no calcium supplementation. Monitor calcium levels and calcium and vitamin D intake.

Hypersensitivity
XGEVA is contraindicated in patients with known clinically significant hypersensitivity to XGEVA, including anaphylaxis that has been reported with use of XGEVA. Reactions may include hypotension, dyspnea, upper airway edema, lip swelling, rash, pruritus, and urticaria. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue XGEVA therapy permanently.

Drug Products with Same Active Ingredient
Patients receiving XGEVA should not take Prolia (denosumab).

Osteonecrosis of the Jaw
Osteonecrosis of the jaw (ONJ) has been reported in patients receiving XGEVA, manifesting as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration, or gingival erosion. Persistent pain or slow healing of the mouth or jaw after dental surgery may also be manifestations of ONJ. In clinical trials in patients with osseous metastasis, the incidence of ONJ was higher with longer duration of exposure.

Patients with a history of tooth extraction, poor oral hygiene, or use of a dental appliance are at a greater risk to develop ONJ. Other risk factors for the development of ONJ include immunosuppressive therapy, treatment with angiogenesis inhibitors, systemic corticosteroids, diabetes, and gingival infections.

Perform an oral examination and appropriate preventive dentistry prior to the initiation of XGEVA and periodically during XGEVA therapy. Advise patients regarding oral hygiene practices. Avoid invasive dental procedures during treatment with XGEVA. Consider temporarily interrupting XGEVA therapy if an invasive dental procedure must be performed.

Patients who are suspected of having or who develop ONJ while on XGEVA should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition.

Atypical Subtrochanteric and Diaphyseal Femoral Fracture
Atypical femoral fracture has been reported with XGEVA. These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution.

Atypical femoral fractures most commonly occur with minimal or no trauma to the affected area. They may be bilateral and many patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs. A number of reports note that patients were also receiving treatment with glucocorticoids (e.g. prednisone) at the time of fracture. During XGEVA treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Patients presenting with an atypical femur fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of XGEVA therapy should be considered, pending a risk/benefit assessment, on an individual basis.

Hypercalcemia Following Treatment Discontinuation in Patients with Growing Skeletons
Clinically significant hypercalcemia has been reported in XGEVA treated patients with growing skeletons, weeks to months following treatment discontinuation. Monitor patients for signs and symptoms of hypercalcemia and treat appropriately.

Embryo-Fetal Toxicity
XGEVA can cause fetal harm when administered to a pregnant woman. Based on findings in animals, XGEVA is expected to result in adverse reproductive effects. Advise females of reproductive potential to use highly effective contraception during therapy, and for at least 5 months after the last dose of XGEVA. Apprise the patient of the potential hazard to a fetus if XGEVA is used during pregnancy or if the patient becomes pregnant while patients are exposed to XGEVA.

Adverse Reactions
The most common adverse reactions in patients receiving XGEVA with bone metastasis from solid tumors were fatigue/asthenia, hypophosphatemia, and nausea. The most common serious adverse reaction was dyspnea.

The most common adverse reactions resulting in discontinuation were osteonecrosis and hypocalcemia. The most common adverse reactions in patients receiving XGEVA for giant cell tumor of bone were arthralgia, headache, nausea, back pain, fatigue, and pain in extremity. The most common serious adverse reactions were osteonecrosis of the jaw and osteomyelitis. The most common adverse reactions resulting in discontinuation of XGEVA were osteonecrosis of the jaw and tooth abscess or tooth infection. The most common adverse reactions in patients receiving XGEVA for hypercalcemia of malignancy were nausea, dyspnea, decreased appetite, headache, peripheral edema, vomiting, anemia, constipation, and diarrhea.

Denosumab is also marketed as Prolia in other indications.

Please visit www.amgen.com or www.xgeva.com for Full U.S. Prescribing Information.

About IMLYGIC
IMLYGIC is a genetically modified herpes simplex type 1 virus that is injected directly into tumors. IMLYGIC replicates inside tumor cells and produces GM-CSF, an immunostimulatory protein. IMLYGIC then causes the cell to rupture and die in a process called lysis. The rupture of the cancer cells causes the release of tumor-derived antigens, which together with virally derived GM-CSF may help to promote an anti-tumor immune response. However, the exact mechanism of action is unknown.

IMLYGIC is the first oncolytic viral therapy approved by the U.S. Food and Drug Administration (FDA) based on therapeutic benefit demonstrated in a pivotal study. IMLYGIC is a genetically modified oncolytic viral therapy indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. IMLYGIC has not been shown to improve overall survival or have an effect on visceral metastases.

Important U.S. Safety Information

Contraindications

Do not administer IMLYGIC to immunocompromised patients, including those with a history of primary or acquired immunodeficient states, leukemia, lymphoma, AIDS or other clinical manifestations of infection with human immunodeficiency viruses, and those on immunosuppressive therapy, due to the risk of life‐threatening disseminated herpetic infection.
Do not administer IMLYGIC to pregnant patients.
Warnings and Precautions

Accidental exposure to IMLYGIC may lead to transmission of IMLYGIC and herpetic infection, including during preparation and administration. Health care providers, close contacts, pregnant women, and newborns should avoid direct contact with injected lesions, dressings, or body fluids of treated patients. The affected area in exposed individuals should be cleaned thoroughly with soap and water and/or a disinfectant.
Caregivers should wear protective gloves when assisting patients in applying or changing occlusive dressings and observe safety precautions for disposal of used dressings, gloves, and cleaning materials. Exposed individuals should clean the affected area thoroughly with soap and water and/or a disinfectant.
To prevent possible inadvertent transfer of IMLYGIC to other areas of the body, patients should be advised to avoid touching or scratching injection sites or occlusive dressings.
Herpetic infections: Herpetic infections (including cold sores and herpetic keratitis) have been reported in IMLYGIC‐treated patients. Disseminated herpetic infection may also occur in immunocompromised patients. Patients who develop suspicious herpes‐like lesions should follow standard hygienic practices to prevent viral transmission.
Patients or close contacts with suspected signs or symptoms of a herpetic infection should contact their health care provider to evaluate the lesions. Suspected herpetic lesions should be reported to Amgen at 1‐855‐IMLYGIC (1‐855‐465‐9442). Patients or close contacts have the option of follow‐up testing for further characterization of the infection.
IMLYGIC is sensitive to acyclovir. Acyclovir or other antiviral agents may interfere with the effectiveness of IMLYGIC. Consider the risks and benefits of IMLYGIC treatment before administering antiviral agents to manage herpetic infection.
Injection Site Complications: Necrosis or ulceration of tumor tissue may occur during IMLYGIC treatment. Cellulitis and systemic bacterial infection have been reported in clinical studies. Careful wound care and infection precautions are recommended, particularly if tissue necrosis results in open wounds.
Impaired healing at the injection site has been reported. IMLYGIC may increase the risk of impaired healing in patients with underlying risk factors (e.g., previous radiation at the injection site or lesions in poorly vascularized areas). If there is persistent infection or delayed healing of the injection site, consider the risks and benefits of continuing treatment.
Immune‐Mediated events including glomerulonephritis, vasculitis, pneumonitis, worsening psoriasis, and vitiligo have been reported in patients treated with IMLYGIC. Consider the risks and benefits of IMLYGIC before initiating treatment in patients who have underlying autoimmune disease or before continuing treatment in patients who develop immune‐mediated events.
Plasmacytoma at the Injection Site: Plasmacytoma in proximity to the injection site has been reported in a patient with smoldering multiple myeloma after IMLYGIC administration in a clinical study. Consider the risks and benefits of IMLYGIC in patients with multiple myeloma or in whom plasmacytoma develops during treatment.
Obstructive Airway Disorder: Obstructive airway disorder has been reported following IMLYGIC treatment. Use caution when injecting lesions close to major airways.
Adverse Reactions

The most commonly reported adverse drug reactions (≥ 25%) in IMLYGIC‐treated patients were fatigue, chills, pyrexia, nausea, influenza‐like illness, and injection site pain. Pyrexia, chills, and influenza‐like illness can occur at any time during IMLYGIC treatment, but were more frequent during the first 3 months of treatment.
The most common Grade 3 or higher adverse reaction was cellulitis.
Please see full Prescribing Information and Medication Guide for IMLYGIC.

About BLINCYTO (blinatumomab)
BLINCYTO is a bispecific CD19-directed CD3 T cell engager (BiTE) antibody construct that binds specifically to CD19 expressed on the surface of cells of B-lineage origin and CD3 expressed on the surface of T cells.

BLINCYTO was granted breakthrough therapy and priority review designations by the FDA, and is now approved in the U.S. for the treatment of Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor ALL. This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials.

In November 2015, BLINCYTO was granted conditional marketing authorization in the EU for the treatment of adults with Ph- relapsed or refractory B-cell precursor ALL.

About BiTE Technology
Bispecific T cell engager (BiTE) antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the body’s immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE antibody constructs are currently being investigated for their potential to treat a wide variety of cancers. For more information, visit www.biteantibodies.com.

BLINCYTO U.S. Product Safety Information

Important Safety Information Regarding BLINCYTO (blinatumomab) U.S. Indication

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES

Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended.
Neurological toxicities, which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended.
Contraindications
BLINCYTO is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.

Warnings and Precautions

Cytokine Release Syndrome (CRS): CRS, which may be life-threatening or fatal, occurred in patients receiving BLINCYTO. Infusion reactions have occurred and may be clinically indistinguishable from manifestations of CRS. Closely monitor patients for signs and symptoms of serious events such as pyrexia, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), disseminated intravascular coagulation (DIC), capillary leak syndrome (CLS), and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Interrupt or discontinue BLINCYTO as outlined in the Prescribing Information (PI).
Neurological Toxicities: Approximately 64% of patients receiving BLINCYTO in clinical trials experienced neurological toxicities. The median time to onset of any neurological toxicity was 4 days. The most common (≥ 10%) manifestations of neurological toxicity were headache, tremor, dizziness, and altered state of consciousness. Severe, life-threatening, or fatal neurological toxicities occurred in approximately 17% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. The neurological toxicity profile varied by age group. Monitor patients for signs or symptoms and interrupt or discontinue BLINCYTO as outlined in the PI.
Infections: Approximately 25% of patients receiving BLINCYTO experienced serious infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO as needed.
Tumor Lysis Syndrome (TLS): TLS, which may be life-threatening or fatal, has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on-treatment hydration, should be used during BLINCYTO treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO as needed to manage these events.
Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters during BLINCYTO infusion and interrupt BLINCYTO if prolonged neutropenia occurs.
Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures, patients receiving BLINCYTO are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO is being administered.
Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO treatment with a median time to onset of 3 days. In patients receiving BLINCYTO, although the majority of these events were observed in the setting of CRS, some cases of elevated liver enzymes were observed outside the setting of CRS, with a median time to onset of 15 days. Grade 3 or greater elevations in liver enzymes occurred in 6% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase (GGT), and TBILI prior to the start of and during BLINCYTO treatment. BLINCYTO treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if TBILI rises to > 3 times ULN.
Pancreatitis: Fatal pancreatitis has been reported in patients receiving BLINCYTO in combination with dexamethasone in clinical trials and the post-marketing setting. Evaluate patients who develop signs and symptoms of pancreatitis and interrupt or discontinue BLINCYTO and dexamethasone as needed.
Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO, especially in patients previously treated with cranial irradiation and antileukemic chemotherapy.
Preparation and administration errors have occurred with BLINCYTO treatment. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).
Immunization: Vaccination with live virus vaccines is not recommended for at least 2 weeks prior to the start of BLINCYTO treatment, during treatment, and until immune recovery following last cycle of BLINCYTO.
Adverse Reactions

The most common adverse reactions (≥ 20%) in the safety population studied in clinical trials were pyrexia (66%), headache (34%), nausea (27%), edema (26%), hypokalemia (26%), anemia (25%), febrile neutropenia (24%), neutropenia (22%), thrombocytopenia (20%), and abdominal pain (20%). The safety population included 225 patients weighing 45 kg or more and 57 patients weighing less than 45 kg. For some adverse reactions, there were differences in the incidence rates by age subgroup.
In patients weighing greater than or equal to 45 kg, serious adverse reactions were reported in 61% of patients. The most common serious adverse reactions (≥ 2%) included febrile neutropenia (9%), pyrexia (6%), sepsis (5%), pneumonia (5%), device-related infection (4%), neutropenia (3%), tremor (3%), overdose (3%), encephalopathy (3%), infection (2%), confusion (3%) and headache (2%).
In patients weighing less than 45 kg, serious adverse reactions were reported in 51% of patients. The most common serious adverse reactions (≥ 2%) included pyrexia (12%), febrile neutropenia (9%), cytokine release syndrome (4%), convulsion (4%), device-related infection (4%), hypoxia (4%), sepsis (4%), and overdose (4%).
U.S. Dosage and Administration Guidelines

BLINCYTO is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which should be programmable, lockable, non-elastomeric, and have an alarm.
It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).
Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide, for BLINCYTO at www.BLINCYTO.com.

About KYPROLIS (carfilzomib)
Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed.2 KYPROLIS has been shown to block proteasomes, leading to an excessive build-up of proteins within cells.2 In some cells, KYPROLIS can cause cell death, especially in myeloma cells because they are more likely to contain a higher amount of abnormal proteins.2,3

KYPROLIS is approved in the U.S. for the following:

In combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.
As a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.
KYPROLIS is also approved in Argentina, Australia, Bahrain, Canada, Hong Kong, Israel, Japan, Kuwait, Lebanon, Macao, Mexico, Thailand, Colombia, S. Korea, Canada, Qatar, Switzerland, United Arab Emirates, Turkey, Russia, Brazil, India, Oman and the European Union. Additional regulatory applications for KYPROLIS are underway and have been submitted to health authorities worldwide.

IMPORTANT SAFETY INFORMATION

Cardiac Toxicities

New onset or worsening of pre-existing cardiac failure (e.g., congestive heart failure, pulmonary edema, decreased ejection fraction), restrictive cardiomyopathy, myocardial ischemia, and myocardial infarction including fatalities have occurred following administration of KYPROLIS. Some events occurred in patients with normal baseline ventricular function. Death due to cardiac arrest has occurred within one day of KYPROLIS administration.
Monitor patients for clinical signs or symptoms of cardiac failure or cardiac ischemia. Evaluate promptly if cardiac toxicity is suspected. Withhold KYPROLIS for Grade 3 or 4 cardiac adverse events until recovery, and consider whether to restart KYPROLIS at 1 dose level reduction based on a benefit/risk assessment.
While adequate hydration is required prior to each dose in Cycle 1, monitor all patients for evidence of volume overload, especially patients at risk for cardiac failure. Adjust total fluid intake as clinically appropriate in patients with baseline cardiac failure or who are at risk for cardiac failure.
Patients ≥ 75 years, the risk of cardiac failure is increased. Patients with New York Heart Association Class III and IV heart failure, recent myocardial infarction, conduction abnormalities, angina, or arrhythmias may be at greater risk for cardiac complications and should have a comprehensive medical assessment (including blood pressure and fluid management) prior to starting treatment with KYPROLIS and remain under close follow-up.
Acute Renal Failure

Cases of acute renal failure and renal insufficiency adverse events (including renal failure) have occurred in patients receiving KYPROLIS. Acute renal failure was reported more frequently in patients with advanced relapsed and refractory multiple myeloma who received KYPROLIS monotherapy. Monitor renal function with regular measurement of the serum creatinine and/or estimated creatinine clearance. Reduce or withhold dose as appropriate.
Tumor Lysis Syndrome

Cases of Tumor Lysis Syndrome (TLS), including fatal outcomes, have occurred in patients receiving KYPROLIS. Patients with multiple myeloma and a high tumor burden should be considered at greater risk for TLS. Adequate hydration is required prior to each dose in Cycle 1, and in subsequent cycles as needed. Consider uric acid lowering drugs in patients at risk for TLS. Monitor for evidence of TLS during treatment and manage promptly. Withhold KYPROLIS until TLS is resolved.
Pulmonary Toxicity

Acute Respiratory Distress Syndrome (ARDS), acute respiratory failure, and acute diffuse infiltrative pulmonary disease such as pneumonitis and interstitial lung disease have occurred in patients receiving KYPROLIS. Some events have been fatal. In the event of drug-induced pulmonary toxicity, discontinue KYPROLIS.
Pulmonary Hypertension

Pulmonary arterial hypertension (PAH) was reported in patients treated with KYPROLIS. Evaluate with cardiac imaging and/or other tests as indicated. Withhold KYPROLIS for PAH until resolved or returned to baseline and consider whether to restart KYPROLIS based on a benefit/risk assessment.
Dyspnea

Dyspnea was reported in patients treated with KYPROLIS. Evaluate dyspnea to exclude cardiopulmonary conditions including cardiac failure and pulmonary syndromes. Stop KYPROLIS for Grade 3 or 4 dyspnea until resolved or returned to baseline. Consider whether to restart KYPROLIS based on a benefit/risk assessment.
Hypertension

Hypertension, including hypertensive crisis and hypertensive emergency, has been observed with KYPROLIS. Some of these events have been fatal. Monitor blood pressure regularly in all patients. If hypertension cannot be adequately controlled, withhold KYPROLIS and evaluate. Consider whether to restart KYPROLIS based on a benefit/risk assessment.
Venous Thrombosis

Venous thromboembolic events (including deep venous thrombosis and pulmonary embolism) have been observed with KYPROLIS. Thromboprophylaxis is recommended for patients being treated with the combination of KYPROLIS with dexamethasone or with lenalidomide plus dexamethasone. The thromboprophylaxis regimen should be based on an assessment of the patient’s underlying risks.
Patients using oral contraceptives or a hormonal method of contraception associated with a risk of thrombosis should consider an alternative method of effective contraception during treatment with KYPROLIS in combination with dexamethasone or lenalidomide plus dexamethasone.
Infusion Reactions

Infusion reactions, including life-threatening reactions, have occurred in patients receiving KYPROLIS.
Symptoms include fever, chills, arthralgia, myalgia, facial flushing, facial edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina. These reactions can occur immediately following or up to 24 hours after administration of KYPROLIS. Premedicate with dexamethasone to reduce the incidence and severity of infusion reactions. Inform patients of the risk and of symptoms of an infusion reaction and to contact a physician immediately if they occur.
Hemorrhage

Fatal or serious cases of hemorrhage have been reported in patients receiving KYPROLIS. Hemorrhagic events have included gastrointestinal, pulmonary, and intracranial hemorrhage and epistaxis. Promptly evaluate signs and symptoms of blood loss. Reduce or withhold dose as appropriate.
Thrombocytopenia

KYPROLIS causes thrombocytopenia with recovery to baseline platelet count usually by the start of the next cycle. Thrombocytopenia was reported in patients receiving KYPROLIS. Monitor platelet counts frequently during treatment with KYPROLIS. Reduce or withhold dose as appropriate.
Hepatic Toxicity and Hepatic Failure

Cases of hepatic failure, including fatal cases, have been reported during treatment with KYPROLIS. KYPROLIS can cause increased serum transaminases. Monitor liver enzymes regularly regardless of baseline values. Reduce or withhold dose as appropriate.
Thrombotic Microangiopathy

Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), including fatal outcome have occurred in patients receiving KYPROLIS. Monitor for signs and symptoms of TTP/HUS. Discontinue KYPROLIS if diagnosis is suspected. If the diagnosis of TTP/HUS is excluded, KYPROLIS may be restarted. The safety of reinitiating KYPROLIS therapy in patients previously experiencing TTP/HUS is not known.
Posterior Reversible Encephalopathy Syndrome (PRES)

Cases of PRES have occurred in patients receiving KYPROLIS. PRES was formerly known as Reversible Posterior Leukoencephalopathy Syndrome. Consider a neuro-radiological imaging (MRI) for onset of visual or neurological symptoms. Discontinue KYPROLIS if PRES is suspected and evaluate. The safety of reinitiating KYPROLIS therapy in patients previously experiencing PRES is not known.
Embryo-fetal Toxicity

KYPROLIS can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals.
Females of reproductive potential should be advised to avoid becoming pregnant while being treated with KYPROLIS. Males of reproductive potential should be advised to avoid fathering a child while being treated with KYPROLIS. If this drug is used during pregnancy, or if pregnancy occurs while taking this drug, the patient should be apprised of the potential hazard to the fetus.
ADVERSE REACTIONS

The most common adverse reactions occurring in at least 20% of patients treated with KYPROLIS in the combination therapy trials: anemia, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia, pyrexia, insomnia, muscle spasm, cough, upper respiratory tract infection, hypokalemia.
The most common adverse reactions occurring in at least 20% of patients treated with KYPROLIS in monotherapy trials: anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea, diarrhea, headache, cough, edema peripheral.
Please see full prescribing information at www.kyprolis.com.

About Vectibix (panitumumab)
Vectibix is the first fully human monoclonal anti-EGFR antibody approved by the FDA for the treatment of mCRC. Vectibix was approved in the U.S. in September 2006 as a monotherapy for the treatment of patients with EGFR-expressing mCRC after disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy.

In May 2014, the FDA approved Vectibix for use in combination with FOLFOX, as first-line treatment in patients with wild-type KRAS (exon 2) mCRC. With this approval, Vectibix became the first-and-only biologic therapy indicated for use with FOLFOX, one of the most commonly used chemotherapy regimens, in the first-line treatment of mCRC for patients with wild-type KRAS mCRC.

Important U.S. Product Information
Vectibix is indicated for the treatment of patients with wild-type KRAS (exon 2 in codons 12 or 13) metastatic colorectal cancer (mCRC) as determined by an FDA-approved test for this use:

As first-line therapy in combination with FOLFOX
As monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy
Limitation of Use: Vectibix is not indicated for the treatment of patients with RAS-mutant mCRC or for whom RAS mutation status is unknown.

WARNING: DERMATOLOGIC TOXICITY
Dermatologic Toxicity: Dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 or higher) in 15% of patients receiving Vectibix monotherapy.

In Study 1, dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients with mCRC receiving Vectibix. The clinical manifestations included, but were not limited to, acneiform dermatitis, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin and skin fissures.

Monitor patients who develop dermatologic or soft tissue toxicities while receiving Vectibix for the development of inflammatory or infectious sequelae. Life-threatening and fatal infectious complications including necrotizing fasciitis, abscesses and sepsis have been observed in patients treated with Life-threatening and fatal bullous mucocutaneous disease with blisters, erosions and skin sloughing has also been observed in patients treated with Vectibix. It could not be determined whether these mucocutaneous adverse reactions were directly related to EGFR inhibition or to idiosyncratic immune-related effects (e.g., Stevens-Johnson syndrome or toxic epidermal necrolysis). Withhold or discontinue Vectibix for dermatologic or soft tissue toxicity associated with severe or life-threatening inflammatory or infectious complications. Dose modifications for Vectibix concerning dermatologic toxicity are provided in the product labeling.

Vectibix is not indicated for the treatment of patients with colorectal cancer that harbor somatic mutations in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of either KRAS or NRAS and hereafter is referred to as "RAS."

Retrospective subset analyses across several randomized clinical trials were conducted to investigate the role of RAS mutations on the clinical effects of anti-EGFR-directed monoclonal antibodies (panitumumab or cetuximab). Anti-EGFR antibodies in patients with tumors containing RAS mutations resulted in exposing those patients to anti-EGFR related adverse reactions without clinical benefit from these agents.

Additionally, in Study 3, 272 patients with RAS-mutant mCRC tumors received Vectibix in combination with FOLFOX and 276 patients received FOLFOX alone. In an exploratory subgroup analysis, OS was shorter (HR = 1.21, 95% CI 1.01-1.45) in patients with RAS-mutant mCRC who received Vectibix and FOLFOX versus FOLFOX alone.

Progressively decreasing serum magnesium levels leading to severe (Grade 3-4) hypomagnesemia occurred in up to 7% (in Study 2) of patients across clinical trials. Monitor patients for hypomagnesemia and hypocalcemia prior to initiating Vectibix treatment, periodically during Vectibix treatment, and for up to 8 weeks after the completion of treatment. Other electrolyte disturbances, including hypokalemia, have also been observed. Replete magnesium and other electrolytes as appropriate.

In Study 1, 4% of patients experienced infusion reactions and 1% of patients experienced severe infusion reactions (NCI-CTC grade 3-4). Infusion reactions, manifesting as fever, chills, dyspnea, bronchospasm, and hypotension, can occur following Vectibix administration. Fatal infusion reactions occurred in postmarketing experience. Terminate the infusion for severe infusion reactions.

Severe diarrhea and dehydration, leading to acute renal failure and other complications, have been observed in patients treated with Vectibix in combination with chemotherapy.

Fatal and non-fatal cases of interstitial lung disease (ILD) (1%) and pulmonary fibrosis have been observed in patients treated with Vectibix. Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix. In the event of acute onset or worsening of pulmonary symptoms, interrupt Vectibix therapy. Discontinue Vectibix therapy if ILD is confirmed.

In patients with a history of interstitial pneumonitis or pulmonary fibrosis, or evidence of interstitial pneumonitis or pulmonary fibrosis, the benefits of therapy with Vectibix versus the risk of pulmonary complications must be carefully considered.

Exposure to sunlight can exacerbate dermatologic toxicity. Advise patients to wear sunscreen and hats and limit sun exposure while receiving Vectibix.

Keratitis and ulcerative keratitis, known risk factors for corneal perforation, have been reported with Vectibix use. Monitor for evidence of keratitis or ulcerative keratitis. Interrupt or discontinue Vectibix for acute or worsening keratitis.

In an interim analysis of an open-label, multicenter, randomized clinical trial in the first-line setting in patients with mCRC, the addition of Vectibix to the combination of bevacizumab and chemotherapy resulted in decreased OS and increased incidence of NCI-CTC grade 3–5 (87% vs 72%) adverse reactions. NCI-CTC grade 3–4 adverse reactions occurring at a higher rate in Vectibix-treated patients included rash/acneiform dermatitis (26% vs 1%), diarrhea (23% vs 12%), dehydration (16% vs 5%; primarily occurring in patients with diarrhea), hypokalemia (10% vs 4%), stomatitis/mucositis (4% vs < 1%), and hypomagnesemia (4% vs 0).

NCI-CTC grade 3–5 pulmonary embolism occurred at a higher rate in Vectibix-treated patients (7% vs 3%) and included fatal events in three (< 1%) Vectibix-treated patients.

As a result of the toxicities experienced, patients randomized to Vectibix, bevacizumab and chemotherapy received a lower mean relative dose intensity of each chemotherapeutic agent (oxaliplatin, irinotecan, bolus 5-FU, and/or infusional 5-FU) over the first 24 weeks on study, compared with those randomized to bevacizumab and chemotherapy.

Advise patients of the need for adequate contraception in both males and females while receiving Vectibix and for 6 months after the last dose of Vectibix therapy. Vectibix may be transmitted from the mother to the developing fetus, and has the potential to cause fetal harm when administered to pregnant women.

Because many drugs are excreted into human milk and because of the potential for serious adverse reactions in nursing infants from Vectibix, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. If nursing is interrupted, it should not be resumed earlier than 2 months following the last dose of Vectibix.

Women who become pregnant during Vectibix treatment are encouraged to enroll in Amgen’s Pregnancy Surveillance Program. Women who are nursing during Vectibix treatment are encouraged to enroll in Amgen’s Lactation Surveillance Program. Patients or their physicians should call 1-800-77-AMGEN (1-800-772-6436) to enroll.

In Study 1, the most common adverse reactions (> 20%) with Vectibix were skin rash with variable presentations, paronychia, fatigue, nausea, and diarrhea. The most common (> 5%) serious adverse reactions in the Vectibix arm were general physical health deterioration and intestinal obstruction.

In Study 3, the most commonly reported adverse reactions (> 20%) in patients with wild-type KRAS mCRC receiving Vectibix (6 mg/kg every 2 weeks) and FOLFOX therapy (N = 322) were diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus and dry skin. Serious adverse reactions (> 2% difference between treatment arms) in Vectibix-treated patients with wild-type KRAS mCRC were diarrhea and dehydration.

To see the Vectibix Prescribing Information, including Boxed Warning visit www.vectibix.com.