On April 26, 2018 Alkermes plc (Nasdaq: ALKS) reported financial results for the first quarter of 2018 (Press release, Alkermes, APR 26, 2018, View Source;p=RssLanding&cat=news&id=2344849 [SID1234525716]).

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"Our first quarter results were in line with our expectations and reflect the solid growth of our proprietary commercial products and the continued strength of our royalty and manufacturing business," commented James Frates, Chief Financial Officer of Alkermes. "Today, we are updating our financial expectations for 2018, driven primarily by the timing of investments we will make in our commercial organization in preparation for the potential launch of ALKS 5461 in 2019. We remain well positioned to execute on our strategy to drive long-term value through important investments in our development pipeline and the growth of VIVITROL and ARISTADA."

Quarter Ended Mar. 31, 2018 Financial Highlights

Total revenues for the quarter were $225.2 million. This compared to $191.8 million for the same period in the prior year, representing an increase of 17%.
Net loss according to generally accepted accounting principles in the U.S. (GAAP) was $62.5 million for the quarter, or a basic and diluted GAAP net loss per share of $0.40. This compared to GAAP net loss of $68.9 million, or a basic and diluted GAAP net loss per share of $0.45 for the same period in the prior year.
Non-GAAP net loss was $14.2 million for the quarter, or a non-GAAP basic and diluted net loss per share of $0.09. This compared to non-GAAP net loss of $27.9 million, or a non-GAAP basic and diluted net loss per share of $0.18 for the same period in the prior year.
"VIVITROL and ARISTADA continue to demonstrate solid growth year-over-year and we have made significant progress in making these important medicines available to patients. We continue to focus on initiatives to promote broad and seamless access for patients," stated Jim Robinson, President and Chief Operating Officer of Alkermes. "The upcoming potential approval and launch of Aripiprazole Lauroxil NanoCrystal Dispersion (ALNCD), a novel, investigational product designed for initiation onto ARISTADA, is an opportunity to address unmet patient need and expand the ARISTADA product family. Similarly, against the backdrop of new data, funding and policy being implemented to address the opioid epidemic, we have an opportunity to further expand patient access to VIVITROL, increase utilization and drive growth."

Quarter Ended Mar. 31, 2018 Financial Results

Revenues

Net sales of VIVITROL were $62.7 million, compared to $58.5 million for the same period in the prior year, representing an increase of approximately 7%.
Net sales of ARISTADA were $29.2 million, compared to $18.0 million for the same period in the prior year, representing an increase of approximately 62%.
Manufacturing and royalty revenues from RISPERDAL CONSTA, INVEGA SUSTENNA/XEPLION and INVEGA TRINZA/TREVICTA were $68.8 million, compared to $60.0 million for the same period in the prior year.
Manufacturing and royalty revenues from AMPYRA/FAMPYRA1 were $28.3 million, compared to $29.2 million for the same period in the prior year.
Research and development revenues from the collaboration with Biogen for BIIB098 (formerly ALKS 8700) were $17.5 million.
Costs and Expenses

Operating expenses were $287.0 million, compared to $262.6 million for the same period in the prior year, primarily reflecting increased investment in the commercialization of VIVITROL and ARISTADA.
Net interest expense during the quarter was $4.0 million and included a $2.3 million charge related to the refinancing of the company’s term loan. The company refinanced its term loan to extend the maturity to 2023 and reduce the interest rate by 0.5%.
"Alkermes is entering the final stages of development for three of our pipeline candidates. The regulatory review of ALKS 5461 is back on track and we continue to prepare for potential approval and launch in 2019. For ALKS 3831, we recently completed enrollment of the ENLIGHTEN-2 pivotal study, with topline data expected in the fourth quarter of 2018. For BIIB098, preparation of the regulatory submission has begun and we are on track to submit the NDA toward year-end," said Richard Pops, Chief Executive Officer of Alkermes. "We are on the threshold of our next phase of growth. Our dedication and determination to bring these important new medicines to patients are steadfast and we look forward to sharing our progress throughout the year."

Recent Events:

ALKS 5461: New Drug Application (NDA) accepted for filing by U.S. Food and Drug Administration (FDA) for the adjunctive treatment of major depressive disorder (MDD) in patients with inadequate response to standard antidepressant therapy. A target action date of Jan. 31, 2019 was assigned under the Prescription Drug User Fee Act (PDUFA).
ALKS 3831: Enrollment completed for ENLIGHTEN-2, a six-month weight study compared to olanzapine in patients with stable schizophrenia. Topline results are expected in the fourth quarter of 2018.
BIIB098: MRI and relapse results from the phase 3 EVOLVE-MS-1 study in patients with relapsing and remitting multiple sclerosis were presented at the 70th annual meeting of the American Academy of Neurology (AAN).
James (Jim) Robinson appointed to the role of President and Chief Operating Officer of Alkermes. Mr. Robinson’s responsibilities include leading Alkermes’ global Commercial, Operations, Business Development and Human Resources functions.
Financial Expectations for 2018

Alkermes is updating its financial expectations for 2018 to reflect the expected timing of potential approval and launch of ALKS 5461 in 2019. The following outlines Alkermes’ updated financial expectations for 2018.

Revenues: The company continues to expect total revenues to range from $975 million to $1.025 billion, driven by continuing growth of VIVITROL and ARISTADA. Included in this total revenue expectation, Alkermes continues to expect VIVITROL net sales to range from $300 million to $330 million, and ARISTADA net sales to range from $140 million to $160 million.
Cost of Goods Manufactured and Sold: The company continues to expect cost of goods manufactured and sold to range from $180 million to $190 million.
Research and Development (R&D) Expenses: The company continues to expect R&D expenses to range from $415 million to $445 million.
Selling, General and Administrative (SG&A) Expenses: The company now expects SG&A expenses to range from $515 million to $545 million, reduced from a previous expectation of $555 million to $585 million. This reduction is driven by the shift into 2019 of certain launch-related expenditures including the hiring of the ALKS 5461 sales force, and share-based compensation expense related to certain company-wide performance-based restricted stock unit awards, which vest upon FDA approval of ALKS 5461.
Amortization of Intangible Assets: The company continues to expect amortization of intangibles to be approximately $65 million.
Net Interest Expense: The company continues to expect net interest expense to be approximately $10 million.
Income Tax Expense: The company continues to expect income tax expense of up to $10 million.
GAAP Net Loss: The company now expects GAAP net loss to range from $210 million to $240 million, or a basic and diluted loss per share of $1.35 to $1.55, based on a weighted average basic and diluted share count of approximately 155 million shares outstanding. This compares to previous expectations of GAAP net loss in the range of $250 million to $280 million, or a basic and diluted loss per share of $1.61 to $1.81, based on a weighted average basic and diluted share count of approximately 155 million shares outstanding.
Non-GAAP Net Income (Loss): The company now expects non-GAAP results to range from a non-GAAP net loss of $10 million to a non-GAAP net income of $20 million, or a non-GAAP basic and diluted loss per share of $0.06 to a non-GAAP diluted earnings per share of $0.12, based on a weighted average basic share count of approximately 155 million shares outstanding and a weighted average diluted share count of approximately 161 million shares outstanding. This compares to previous expectations of non-GAAP net loss in the range of $5 million to $35 million, or a basic and diluted non-GAAP net loss per share of $0.03 to $0.23, based on a weighted average basic and diluted share count of approximately 155 million shares outstanding.
Share-Based Compensation: The company now expects share-based compensation of approximately $120 million, reduced from approximately $140 million. This reflects the anticipated timing of vesting of certain company-wide performance-based restricted stock unit awards, which vest upon FDA approval of ALKS 5461.
Capital Expenditures: The company continues to expect capital expenditures to range from $80 million to $90 million.
Conference Call

Alkermes will host a conference call and webcast presentation with accompanying slides at 8:30 a.m. ET (1:30 p.m. BST) on Thursday, Apr. 26, 2018, to discuss these financial results and provide an update on the company. The webcast may be accessed on the Investors section of Alkermes’ website at www.alkermes.com. The conference call may be accessed by dialing +1 888 424 8151 for U.S. callers and +1 847 585 4422 for international callers. The conference call ID number is 6037988. In addition, a replay of the conference call will be available from 11:00 a.m. ET (4:00 p.m. BST) on Thursday, Apr. 26, 2018, through 5:00 p.m. ET (10:00 p.m. BST) on Thursday, May 3, 2018, and may be accessed by visiting Alkermes’ website or by dialing +1 888 843 7419 for U.S. callers and +1 630 652 3042 for international callers. The replay access code is 6037988.

On April 26, 2018 Exact Sciences Corp. (Nasdaq: EXAS) reported that the company generated revenue of $90.3 million and completed approximately 186,000 Cologuard tests during the quarter ended Mar. 31, 2018 (Press release, Exact Sciences, APR 26, 2018, View Source [SID1234525738]). First-quarter 2018 revenue and Cologuard test volume both grew 87 percent from 2017.

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"The Exact Sciences team delivered strong growth to start the year by remaining relentlessly focused on our core priorities. By increasing awareness and adoption of Cologuard, we are making strides toward our mission of playing a role in the eradication of colon cancer," said Kevin Conroy, chairman and CEO of Exact Sciences. "The success of Cologuard also positions us to develop tests that facilitate the early, accurate detection of other forms of cancer."

First-Quarter 2018 Financial Results

For the three-month period ended Mar. 31, 2018, as compared to the same period of 2017 (where applicable):

Revenue was $90.3 million, an increase of 87 percent, and test volume was 186,000, an increase of 87 percent

Average recognized revenue per test was unchanged at $485; note that the prior period included approximately $4.3 million, or $43 per test, related to the one-time impact of certain payers meeting the company’s revenue recognition criteria for accrual-basis revenue accounting

Average cost per test was $123, an improvement of 28 percent

Gross margin was 75 percent, an increase of 970 basis points

Operating expenses were $103.9 million, an increase of 55 percent

Net loss was $39.4 million or $0.33 per share, compared to $34.9 million or $0.32 per share

Non-cash interest expense related to convertible debt was $5.1 million, or $0.04 per share

Cash utilization was $53.7 million, compared to $36.4 million

Cash, cash equivalents and marketable securities were $1.0 billion at the end of the quarter

Nearly 9,000 healthcare providers ordered their first Cologuard test during the first quarter, and 110,000 (rounded) have ordered since the test was launched

2018 Outlook

·The company continues to anticipate revenue of $420-$430 million and completed Cologuard test volume of 900,000-920,000 tests during 2018

·For the second quarter, the company anticipates completing 220,000-230,000 Cologuard tests

The company’s guidance for revenue and completed tests are forward-looking statements. They are subject to various risks and uncertainties that could cause the company’s actual results to differ materially from the anticipated targets. There can be no assurance the company will meet these financial projections. See the cautionary information about forward-looking statements in the "Safe Harbor Statement" section of this press release.

First-Quarter Conference Call & Webcast

Company management will host a conference call and webcast on Thursday, Apr. 26, 2018, at 5 p.m. ET to discuss first-quarter 2018 results. The webcast will be available at www.exactsciences.com. Domestic callers should dial 877-201-0168 and international callers should dial +1-647-788-4901.

An archive of the webcast will be available at www.exactsciences.com. A replay of the conference call will be available by calling 800-585-8367 domestically or 416-621-4642 internationally. The access code for the replay of the call is 8289286. The webcast, conference call and replay are open to all interested parties.

About Cologuard

Cologuard was approved by the FDA in August 2014 and results from Exact Sciences’ prospective 90-site, point-in-time, 10,000-patient pivotal trial were published in the New England Journal of Medicine in March 2014. Cologuard is included in the American Cancer Society’s (2014) colorectal cancer screening guidelines and the recommendations of the U.S. Preventive Services Task Force (2016) and National Comprehensive Cancer Network (2016). Cologuard is indicated to screen adults of either sex, 50 years or older, who are at average risk

for colorectal cancer. Cologuard is not for everyone and is not a replacement for diagnostic colonoscopy or surveillance colonoscopy in high-risk individuals. False positives and false negatives do occur. Any positive test result should be followed by a diagnostic colonoscopy. Following a negative result, patients should continue participating in a screening program at an interval and with a method appropriate for the individual patient. Cologuard performance when used for repeat testing has not been evaluated or established. For more information about Cologuard, visit www.cologuardtest.com. Rx Only

On April 26, 2018 Ono Pharmaceutical Co., Ltd. (Osaka, Japan; President, Representative Director, Gyo Sagara; "ONO") reported that it submitted an application for manufacturing and marketing approval of metyrosine (ONO-5371), a tyrosine hydroxylase inhibitor, for the improvement of status of catecholamine excess secretion and its accompanying symptoms in patients with pheochromocytoma in Japan (Press release, Ono, APR 26, 2018, View Source [SID1234584588]).

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This application is based on a multi-center, open-label, non-comparative study and its
accompanying continuous administration study, Phase I/II study (ONO-5371-02), in patients with the symptoms associated with catecholamine excess secretion of pheochromocytoma, conducted in Japan.

Pheochromocytoma (PC) is a neuroendocrine tumor deriving from the adrenal medulla or the extraadrenal gland ganglion with 2,920 patients estimated in Japan. Catecholamine excessively produced from PC causes various symptoms, such as tachycardia, headache, palpitation, sweating, constipation,including hypertension. Sympatholytic drugs, α-blocker and β-blocker, for control of blood pressure and heart rate have been usually used to improve these symptoms. As there aremany cases where surgical removal of tumors is not applicable in patients with locally invasive or metastatic malignant PC, a long-term therapy, such as radiotherapy and chemotherapy is required. The chronic continuation of catecholamine excess secretion may increase a risk of causing cardiovascular-related adverse events such as heart failure or fatal arrhythmia.

Metyrosine is a product for which development companies were recruited in Japan at the "Review Committee on Unapproved or Off-label Drugs with High Medical Needs", established by the Ministry of Health, Labour and Welfare (MHLW). Further, in May 2015, the product was designated for the orphan drug by the MHLW for the indication of "Improvement of status of catecholamine excess secretion and its accompanying symptoms in patients with PC".

ONO obtained exclusive rights to develop and commercialize metyrosine in Japan for the
prevention, treatment and diagnosis of PC (and conditions and symptoms related thereto), in accordance with the license agreement concluded in October 2013 with Valeant Pharmaceuticals North America LLC (Valeant), an affiliate of Valeant Pharmaceuticals International, Inc. In the US, Valeant markets metyrosine under the tradename of "Demser" in the indication of PC.

Methyrosine
Metyrosine inhibits tyrosine hydroxylase related to the production of catecholamine, reduces catecholamine extremely produced from PC, and alleviates symptoms due to catecholamine excess secretion. Therefore, metyrosine is a promising drug with an efficacy in the improvement of the symptoms in patients who are not able to sufficiently control the symptoms with sympatholytic drugs.

On April 26, 2018 BioCryst Pharmaceuticals, Inc. (NASDAQ:BCRX) reported that its first quarter 2018 financial results will be reported on Tuesday, May 8, 2018 (Press release, BioCryst Pharmaceuticalsa, APR 26, 2018, View Source [SID1234525717]).

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BioCryst will host a conference call and webcast at 11:00 a.m. Eastern Time to discuss financial results and to provide an update regarding the Company’s clinical development programs. The call will be led by Jon P. Stonehouse, President & Chief Executive Officer, Thomas R. Staab II, Senior Vice President & Chief Financial Officer, and Dr. Bill Sheridan, Senior Vice President and Chief Medical Officer.

Links to a live audio webcast and replay of the presentation may be accessed on the BioCryst website events page at View Source

On April 26, 2018 Exelixis, Inc. (NASDAQ:EXEL) reported that data from clinical trials of cabozantinib will be the subject of 15 presentations at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2018 Annual Meeting in Chicago, June 1-5, 2018 (Press release, Exelixis, APR 26, 2018, View Source;p=RssLanding&cat=news&id=2344886 [SID1234525739]).

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Poster presentations will include detailed subset results from the CELESTIAL phase 3 pivotal trial in advanced hepatocellular carcinoma (HCC) comparing outcomes by age and in patients whose only prior treatment was sorafenib. CELESTIAL was the basis for Exelixis’ supplemental New Drug Application filed with the U.S. Food and Drug Administration for CABOMETYX (cabozantinib) tablets as a treatment for patients with previously treated advanced HCC. Additionally, longer follow-up data from the phase 1 trial of cabozantinib in combination with nivolumab with or without ipilimumab in patients with metastatic genitourinary cancers will be featured, along with preliminary safety and efficacy data on cabozantinib plus nivolumab in patients with metastatic urothelial carcinoma refractory to checkpoint inhibitor therapy.

"We’re excited about the potential of cabozantinib, both alone and in combination with other therapies, across a range of difficult-to-treat cancers and look forward to presenting data from our clinical trials in genitourinary cancers, advanced hepatocellular carcinoma and other tumor types," said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. "Our data at ASCO (Free ASCO Whitepaper) underscore our dedication to maximizing results and expanding possibilities for people living with many different cancer types."

Cabozantinib to be featured in 15 presentations
The full schedule of cabozantinib presentations expected at the meeting is as follows:

Poster Discussion

[Abstract 4019] "Cabozantinib (C) versus Placebo (P) in Patients (pts) with Advanced Hepatocellular Carcinoma (HCC) who have Received Prior Sorafenib: Results from the Randomized Phase 3 CELESTIAL Trial"
Ghassan K. Abou-Alfa, M.D., Memorial Sloan Kettering Cancer Center
Session: Gastrointestinal (Noncolorectal) Cancer
Poster presented Sunday, June 3, 8:00 – 11:30 a.m., CDT, Hall A
Discussed at the Poster Discussion Session on Sunday, June 3, 4:45 – 6:00 p.m., CDT, Hall D2

Poster Presentations

[Abstract 4528] "Clinical Efficacy Of Cabozantinib Plus Nivolumab (CaboNivo) and CaboNivo Plus Ipilimumab (CaboNivoIpi) in Patients (pts) with Chemotherapy-refractory Metastatic Urothelial Carcinoma (mUC) either Naïve (n) or Refractory (r) to Checkpoint Inhibitor (CPI)"
Rosa Maria Nadal, M.D., M.D., Ph.D., National Cancer Institute, National Institutes of Health
Session: Genitourinary (Nonprostate) Cancer
Poster presented Saturday, June 2, 8:00 – 11:30 a.m. CDT, Hall A

[Abstract 4556] "Quality-Adjusted Time without Symptoms or Toxicity (Q-TWiST): Analysis of Cabozantinib (Cabo) vs Sunitinib (Sun) in Patients with Advanced Renal Cell Carcinoma (aRCC) of Intermediate or Poor Risk (Alliance A031203)"
Ronald C. Chen, M.D., MPH, University of North Carolina at Chapel Hill
Session: Genitourinary (Nonprostate) Cancer
Poster presented Saturday, June 2, 8:00 – 11:30 a.m. CDT, Hall A

[Abstract 4579] "Cabozantinib (Cabo) in Advanced Non-clear Cell Renal Cell Carcinoma (nccRCC): A Retrospective Multicenter Analysis"
Nieves Martinez Chanza, Dana-Farber Cancer Institute
Session: Genitourinary (Nonprostate) Cancer
Poster presented Saturday, June 2, 8:00 – 11:30 a.m. CDT, Hall A

[Abstract TPS4593] "A Phase I-II Study to Evaluate Safety and Efficacy of the Combination of Niraparib plus Cabozantinib in Patients with Advanced Kidney/Urothelial Carcinoma"
Daniel E. Castellano, M.D., Hospital 12 de Octubre
Session: Genitourinary (Nonprostate) Cancer
Poster presented Saturday, June 2, 8:00 – 11:30 a.m. CDT, Hall A

[Abstract TPS4598] "A Phase 3, Randomized, Open-Label Study of Nivolumab Combined with Cabozantinib vs Sunitinib in Patients with Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (RCC; CheckMate 9ER)"
Toni K. Choueiri, M.D., Dana-Farber Cancer Institute
Session: Genitourinary (Nonprostate) Cancer
Poster presented Saturday, June 2, 8:00 – 11:30 a.m. CDT, Hall A

[Abstract TPS4601] "CANTATA: A Randomized Phase 2 Study of CB-839 in Combination with Cabozantinib vs. Placebo with Cabozantinib in Patients with Advanced/Metastatic Renal Cell Carcinoma"
Nizar M. Tannir, M.D., FACP, The University of Texas MD Anderson Cancer Center
Session: Genitourinary (Nonprostate) Cancer
Poster presented Saturday, June 2, 8:00 – 11:30 a.m. CDT, Hall A

[Abstract TPS4603] "CABOPRE: Phase II Study of Cabozantinib Prior to Cytoreductive Nephrectomy (CN) in Locally Advanced and/or Metastatic Renal Cell Carcinoma (mRCC)"
Guillermo de Velasco, M.D., Ph.D., Department of Medical Oncology, University Hospital 12 de Octubre, i + 12, Madrid, Spain
Session: Genitourinary (Nonprostate) Cancer
Poster presented Saturday, June 2, 8:00 – 11:30 a.m. CDT, Hall A

[Abstract 1026] "A Phase II Study of Cabozantinib (Cabo) Alone or in Combination with Trastuzumab (T) in Patients (pts) with Breast Cancer Brain Metastases (BCBM)"
Jose Pablo Leone, M.D., Dana-Farber Cancer Institute
Session: Breast Cancer – Metastatic
Poster presented Saturday, June 2, 8:00 – 11:30 a.m. CDT, Hall A

[Abstract TPS1119] "A Phase II Study of Nivolumab in Combination with Cabozantinib for Metastatic Triple-Negative Breast Cancer (mTNBC)"
Romualdo Barroso-Sousa, M.D., Ph.D., Dana-Farber Cancer Institute
Session: Breast Cancer – Metastatic
Poster presented Saturday, June 2, 8:00 – 11:30 a.m. CDT, Hall A

[Abstract 6088] "A Phase II Trial of Cabozantinib (CABO) for the Treatment of Radioiodine (RAI)-Refractory Differentiated Thyroid Carcinoma (DTC) in the First-line Setting"
Marcia S. Brose, M.D., Ph.D., Department of Otorhinolaryngology, Head and Neck Surgery and the Abramson Cancer Center of the University of Pennsylvania
Session: Head and Neck Cancer
Poster presented Saturday, June 2, 1:15 – 4:45 p.m. CDT, Hall A

[Abstract 3555] "A Phase I/II Trial of Cabozantinib (C) with or without Panitumumab (P) in Patients (pts) with RAS Wild-Type (WT) Metastatic Colorectal Cancer (mCRC): Clinical Outcomes in Pts with MET Amplification (amp) Detected in Blood"
Jingquan Jia, M.D., Ph.D., Duke University Medical Center
Session: Gastrointestinal (Colorectal) Cancer
Poster presented Sunday, June 3, 8:00 – 11:30 a.m., CDT, Hall A

[Abstract 4088] "Outcomes in Patients (pts) who had Received Sorafenib (S) as the Only Prior Systemic Therapy in the Phase 3 CELESTIAL Trial of Cabozantinib (C) versus Placebo (P) in Advanced Hepatocellular Carcinoma (HCC)"
Robin Kate Kelley, M.D., University of California San Francisco
Session: Gastrointestinal (Noncolorectal) Cancer
Poster presented Sunday, June 3, 8:00 – 11:30 a.m., CDT, Hall A

[Abstract 4090] "Outcomes Based on Age in the Phase 3 CELESTIAL Trial of Cabozantinib (C) versus Placebo (P) in Patients (pts) with Advanced Hepatocellular Carcinoma (HCC)"
Lorenza Rimassa, M.D., Humanitas Clinical and Research Center
Session: Gastrointestinal (Noncolorectal) Cancer
Poster presented Sunday, June 3, 8:00 – 11:30 a.m., CDT, Hall A

[Abstract TPS4157] "A Phase II Trial of Cabozantinib and Erlotinib for Patients with EGFR and c-MET Co-expressing Metastatic Pancreatic Adenocarcinoma"
Olumide B. Gbolahan, MBBS, Indiana University School of Medicine
Session: Gastrointestinal (Noncolorectal) Cancer
Poster presented Sunday, June 3, 8:00 – 11:30 a.m., CDT, Hall A

About the CELESTIAL Study
CELESTIAL is a randomized, double-blind, placebo-controlled study of cabozantinib in patients with advanced HCC conducted at more than 100 sites globally in 19 countries. The trial was designed to enroll 760 patients with advanced HCC who received prior sorafenib and may have received up to two prior systemic cancer therapies for HCC and had adequate liver function. Enrollment of the trial was completed in September 2017. Patients were randomized 2:1 to receive 60 mg of cabozantinib once daily or placebo and were stratified based on etiology of the disease (hepatitis C, hepatitis B or other), geographic region (Asia versus other regions) and presence of extrahepatic spread and/or macrovascular invasion (yes or no). No cross-over was allowed between the study arms during the blinded treatment phase of the trial. The primary endpoint for the trial is overall survival, and secondary endpoints include objective response rate and progression-free survival. Exploratory endpoints include patient-reported outcomes, biomarkers and safety.

About Genitourinary Cancers
Genitourinary cancers are those that affect the urinary tract, bladder, kidneys, ureter, prostate, testicles, penis or adrenal glands — parts of the body involved in reproduction and excretion — and include renal cell carcinoma (RCC) and urothelial carcinoma.1

The American Cancer Society’s 2018 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.2 Clear cell RCC is the most common type of kidney cancer in adults.3 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 12 percent, with no identified cure for the disease.4 Approximately 30,000 patients in the U.S. and 70,000 globally require treatment.5

Urothelial cancers encompass carcinomas of the bladder, ureter and renal pelvis at a ratio of 50:3:1, respectively.6 Urothelial carcinoma occurs mainly in older people; 90 percent of patients with bladder cancer are 55 years or older.7 Bladder cancer is the fourth most common cancer in men and accounts for about five percent of all new cases of cancer in the U.S. each year.7,8 In 2015, an estimated 708,000 people were living with bladder cancer in the U.S.8

About HCC
Liver cancer is the second-leading cause of cancer death worldwide, accounting for more than 700,000 deaths and nearly 800,000 new cases each year.9 In the U.S., the incidence of liver cancer has more than tripled since 1980.2 HCC is the most common form of liver cancer, making up about three-fourths of the estimated nearly 42,000 new cases in the U.S. in 2018. HCC is the fastest-rising cause of cancer-related death in U.S.10 Without treatment, patients with advanced HCC usually survive less than 6 months.11

About CABOMETYX (cabozantinib)
CABOMETYX tablets are approved in the United States for the treatment of patients with advanced RCC. CABOMETYX tablets are also approved in the European Union, Norway, Iceland, Australia, Switzerland and South Korea for the treatment of advanced RCC in adults who have received prior VEGF-targeted therapy. Ipsen also submitted to the EMA the regulatory dossier for cabozantinib as a treatment for first-line advanced RCC in the European Union on August 28, 2017; on March 23, 2018, the CHMP provided a positive opinion for CABOMETYX for the first-line treatment of intermediate- or poor-risk advanced RCC. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan, including RCC.

Please see Important Safety Information below and full U.S. prescribing information at View Source

U.S. Important Safety Information

Hemorrhage: Severe and fatal hemorrhages have occurred with CABOMETYX. In two RCC studies, the incidence of Grade ≥ 3 hemorrhagic events was 3% in CABOMETYX-treated patients. Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.
Gastrointestinal (GI) Perforations and Fistulas: In RCC studies, fistulas were reported in 1% of CABOMETYX-treated patients. Fatal perforations occurred in patients treated with CABOMETYX. In RCC studies, gastrointestinal (GI) perforations were reported in 1% of CABOMETYX-treated patients. Monitor patients for symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a fistula which cannot be appropriately managed or a GI perforation.
Thrombotic Events: CABOMETYX treatment results in an increased incidence of thrombotic events. In RCC studies, venous thromboembolism occurred in 9% (including 5% pulmonary embolism) and arterial thromboembolism occurred in 1% of CABOMETYX-treated patients. Fatal thrombotic events occurred in the cabozantinib clinical program. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or any other arterial thromboembolic complication.
Hypertension and Hypertensive Crisis: CABOMETYX treatment results in an increased incidence of treatment-emergent hypertension, including hypertensive crisis. In RCC studies, hypertension was reported in 44% (18% Grade ≥ 3) of CABOMETYX-treated patients. Monitor blood pressure prior to initiation and regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume CABOMETYX at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy. Discontinue CABOMETYX if there is evidence of hypertensive crisis or severe hypertension despite optimal medical management.
Diarrhea: In RCC studies, diarrhea occurred in 74% of patients treated with CABOMETYX. Grade 3 diarrhea occurred in 11% of patients treated with CABOMETYX. Withhold CABOMETYX in patients who develop intolerable Grade 2 diarrhea or Grade 3-4 diarrhea that cannot be managed with standard antidiarrheal treatments until improvement to Grade 1; resume CABOMETYX at a reduced dose.
Palmar-Plantar Erythrodysesthesia (PPE): In RCC studies, palmar-plantar erythrodysesthesia (PPE) occurred in 42% of patients treated with CABOMETYX. Grade 3 PPE occurred in 8% of patients treated with CABOMETYX. Withhold CABOMETYX in patients who develop intolerable Grade 2 PPE or Grade 3 PPE until improvement to Grade 1; resume CABOMETYX at a reduced dose.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS), a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in the cabozantinib clinical program. Perform an evaluation for RPLS in any patient presenting with seizures, headache, visual disturbances, confusion or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.
Embryo-fetal Toxicity may be associated with CABOMETYX. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during CABOMETYX treatment and for 4 months after the last dose.
Adverse Reactions: The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, nausea, decreased appetite, hypertension, PPE, weight decreased, vomiting, dysgeusia, and stomatitis.
Strong CYP3A4 Inhibitors: If concomitant use with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage.
Strong CYP3A4 Inducers: If concomitant use with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage.
Lactation: Advise women not to breastfeed while taking CABOMETYX and for 4 months after the final dose.
Hepatic Impairment: In patients with mild to moderate hepatic impairment, reduce the CABOMETYX dosage. CABOMETYX is not recommended for use in patients with severe hepatic impairment.
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