On August 1, 2017 AIMM Therapeutics BV, an oncology focused developer of novel tumor specific therapeutic antibodies sourced directly from elite responders to immune therapy or from immunized animals, reported that it has entered into an exclusive license and option agreement with Merck & Co., Inc., Kenilworth, NJ, USA (known as MSD outside the United States and Canada) regarding a series of AIMM’s tumor specific antibodies directed against an undisclosed target expressed on many different tumor types (Press release, AIMM Therapeutics, AUG 1, 2017, View Source [SID1234521097]). In addition, MSD has an exclusive option on a second series of AIMM’s tumor specific antibodies directed against a different tumor target.

Under the terms of the agreement between AIMM and MSD, through a subsidiary, MSD will make an undisclosed upfront payment and future success-based payments. MSD will be responsible for development, manufacturing and commercialization. Additional details were not disclosed.

“We are excited that MSD, as a leader in the field of immuno-oncology, recognizes the unique synergy and clinical potential offered by AIMM’s tumor specific antibodies in combination with KEYTRUDA (pembrolizumab) for cancer patients who have limited or no responses to checkpoint inhibitors alone” said Jan de Vries, AIMM’s CEO.

On August 1, 2017 Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in Hematology and Oncology, reported the Company has completed enrollment with 405 patients randomized in the ROLONTIS Phase 3 ADVANCE pivotal study under a Special Protocol Assessment (SPA) with the Food and Drug Administration (Press release, Spectrum Pharmaceuticals, AUG 1, 2017, View Source [SID1234519979]). The study is evaluating the safety and efficacy of ROLONTIS in the management of chemotherapy-induced neutropenia in patients with breast cancer.

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"I am pleased to report that we have been able to complete enrollment in the ADVANCE study ahead of schedule," said Rajesh C. Shrotriya, MD, Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. "We plan to announce topline data early next year and expect to file a BLA in 2018. RECOVER, the second Phase 3 study for ROLONTIS, is a smaller study that will include sites in the U.S. and Europe, and is currently enrolling patients. RECOVER will leverage established relationships with U.S. sites from the ADVANCE study to help expedite enrollment. We believe ROLONTIS, if approved by the FDA, has the opportunity to change the growth trajectory of our Company because it targets a multi-billion dollar market and our team has a deep knowledge and understanding of the space. We are excited to be in the final stages of what could be a transformational development for the Company."

Spectrum is conducting a second Phase 3 study, RECOVER, which is a multicenter, randomized, active-controlled study similar in design to the ADVANCE study that is currently enrolling in the U.S. and Europe. This study will enroll approximately 218 early-stage breast cancer patients, who will receive adjuvant or neoadjuvant TC (docetaxel and cyclophosphamide) chemotherapy every 21 days for up to 4 cycles. Adjuvant chemotherapy is treatment given after primary surgical therapy to kill any remaining cancer cells and increase the chance of long-term, disease-free survival; neoadjuvant chemotherapy is the administration of cytotoxic agents before surgical resection in early-stage breast cancer to help shrink the tumor and potentially allow for breast-conserving surgery. The primary study endpoint is the Duration of Severe Neutropenia (Absolute Neutrophil Counts [ANC] < 0.5×109/L) in Cycle 1 of chemotherapy, based on central laboratory assessment of ANC over the 21 day cycle. Secondary endpoints include the incidence of neutropenic complications, incidence of febrile neutropenia, relative dose intensity, and safety.

On August 1, 2017 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on the development of potentially curative therapeutics using CRISPR technology, reported financial and operational results for the second quarter of 2017 (Press release, Intellia Therapeutics, AUG 1, 2017, View Source [SID1234519971]).

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The company has made significant progress using our proprietary lipid nanoparticle (LNP) delivery system throughout the quarter. We advanced into non-human primate studies, while first time data from rat studies, the second species we tested in vivo, confirmed the durable mouse data demonstrating high levels of sustained genome editing and serum transthyretin (TTR) reduction post-single-dose intravenous administration.

"We are very excited that our initial non-human primate data in vivo continue to validate our mRNA delivery technology. These preclinical data accelerate our momentum as we advance the development of potential therapies to treat patients with high unmet medical needs," said Chief Executive Officer and founder Nessan Bermingham, Ph.D., Intellia Therapeutics. "During the quarter, we have further strengthened our company by advancing partnerships, including a research agreement with Ospedale San Raffaele in Milan for our ex vivo technology focused on novel engineered cell therapies using CRISPR, expanded our global intellectual property portfolio, and appointed two new members to our Board of Directors."

Second Quarter 2017 Operational Highlights

The company achieved several key operational milestones during the second quarter of 2017, including:

Commenced non-human primate studies in support of our preclinical work relating to our lead development program in TTR. We demonstrated robust green fluorescent protein expression throughout non-human primate liver 24 hours after a single systemically delivered administration dose in vivo, using our proprietary lipid nanoparticle delivery system.

Extended our data set beyond the mouse and delivered CRISPR/Cas9 in the rat. Specifically, initial data from rat models post-single-dose intravenous administration in vivo using our proprietary lipid nanoparticle delivery system showed up to 91 percent reduction in serum TTR protein levels and up to 66 percent editing at the target DNA site, demonstrating robust and dose-responsive gene editing of TTR. We presented these results at the American Society of Gene & Cell Therapy Annual Meeting in Washington D.C. in May 2017.

Provided an update on our ongoing durability study, demonstrating durable liver editing through nine-months post a single intravenous dose administration in mice using our proprietary lipid nanoparticle delivery system. Throughout the liver, the data continues to demonstrate durability and high editing efficiency of LNP-mediated editing of the TTR gene, showing 97 percent reduction in serum TTR protein levels and approximately 70 percent editing at the target DNA site. The intended transient nature of LNP delivery has been confirmed in rodents with undetectable Cas9 mRNA and gRNA levels in the liver by 72 hours post administration.

Entered into a three-year research collaboration, option, and license agreement to engineer optimized T cell cancer therapies with a leading scientific research institution, Ospedale San Raffaele SRL of Milan, Italy.
• The collaboration aims to discover innovative targets against tough-to-treat cancers, leveraging Intellia’s proprietary CRISPR/Cas9 platform to generate next-generation T cell therapies to address unmet needs in hematological and solid tumors.
• The collaboration is the first partnership of Intellia’s eXtellia division, focused on advancing next generations of engineered cell therapies through unique and proprietary applications of CRISPR genome editing in areas including immuno-oncology and auto-immunity.

Continued to defend and enhance our CRISPR/Cas9 foundational and therapeutic intellectual property position through filing and prosecution of patent applications covering our internal, collaboration and in-licensed inventions. In relation to the foundational CRISPR/Cas9 genome editing intellectual property portfolio to which we have rights for human therapeutics and companion diagnostics, and which is co-owned by the Regents of the University of California, the University of Vienna, and Dr. Emmanuelle Charpentier (collectively "UC"), the following was achieved:
• China’s State Intellectual Property Office granted to UC a patent broadly covering CRISPR/Cas9 single-guide genome editing methods and compositions. The patent includes claims that cover methods for editing DNA in non-cellular and cellular settings, including in eukaryotic cells such as human and mammalian cells. It also includes CRISPR/Cas9 composition of matter and system claims for use in any setting, including claims covering the use of CRISPR/Cas9 in producing medicines for treating disease.
• UC submitted its opening brief July 25, 2017 to the U.S. Court of Appeals for the Federal Circuit in their appeal from a February 15, 2017 decision by the U.S. Patent and Trademark Office’s Patent Trial and Appeal Board ("PTAB") in an interference proceeding relating to the CRISPR/Cas9 genome editing technology. In the appeal, UC requests the reversal of the PTAB’s decision to terminate the interference between certain CRISPR/Cas9 patent claims owned by UC and patents and patent applications owned by the Broad Institute, Massachusetts Institute of Technology, the President and Fellows of Harvard College and the Rockefeller University.

Named Moncef Slaoui, Ph.D. and Frank Verwiel, M.D. to its Board of Directors. In addition the Board established a Science & Technology Committee:
• Moncef Slaoui, Ph.D. and Frank Verwiel, M.D. joined the Board of Directors. Drs. Slaoui and Verwiel began Board responsibilities on July 25, 2017. Intellia’s Board of Directors also established a Science and Technology Committee, which will be chaired by Dr. Slaoui. Additionally, Carl L. Gordon, Ph.D., CFA, General Partner, OrbiMed Advisors, LLC, informed the company of his resignation from the Intellia Board of Directors effective at the close of business on July 25, 2017.
Second Quarter 2017 Financial Results

Collaboration Revenue

Collaboration revenue was $5.9 million for the second quarter of 2017, compared to $4.2 million for the second quarter of the prior year. The increase in collaboration revenue in 2017 was primarily driven by amounts recognized under our collaboration agreement with Regeneron Pharmaceuticals, Inc. (Regeneron), which was entered into in April 2016.

Through June 30, 2017, the company received $104.1 million in funding under its collaborations with Novartis Institutes for BioMedical Research, Inc. (Novartis) and Regeneron, excluding amounts received for equity investments, and recorded accounts receivable of $2.8 million. Excluding the $2.6 million of the upfront payment received from Novartis, which was allocated to the purchase of equity securities, we recognized $34.7 million in collaboration revenue under these agreements through June 30, 2017, and had remaining deferred revenue of $69.6 million as of June 30, 2017.

Operating Expenses

Research and development expenses increased $8.2 million to $15.6 million during the second quarter 2017, compared to $7.4 million during the same period of 2016. This increase was driven primarily by greater support for the advancement of our early-stage research programs and includes laboratory supplies and research materials. Additionally, salary and related headcount-based expenses increased as the company grew to 110 research and development employees as of June 30, 2017, from 56 research and development employees as of June 30, 2016.

General and administrative expenses increased $2.7 million to $6.4 million during the second quarter of this year, compared to $3.7 million in the second quarter of 2016. This increase was driven primarily by increased salary and related headcount-based expenses as the company grew to 33 general and administrative employees as of June 30, 2017, from 19 general and administrative employees as of June 30, 2016, to support our public company compliance and administration obligations. The company also incurred increased corporate insurance, legal, and other professional expenses related to its expanding operations since becoming a public company in May 2016.

Our net loss was $15.6 million for the second quarter 2017, compared to $6.9 million for the second quarter of 2016.

Balance Sheet

Cash and cash equivalents at June 30, 2017, were $241 million, compared to $301 million for the same quarter in 2016. The base period cash and cash equivalents were primarily attributable to $115.5 million in proceeds from our initial public offering, $55 million in concurrent private placements, and a $75 million upfront payment from Regeneron in April 2016. The year-over-year change is attributed to cash used in ongoing operations.

Financial Guidance

Our primary uses of capital will continue to be research and development programs, laboratory and related supplies, compensation and related expenses, legal and other regulatory expenses, patent prosecution, filing and maintenance costs for our licensed intellectual property, and general overhead costs.

During 2017, the company expects expenses to continue to increase compared to prior periods relating to our ongoing activities, particularly as research and development and preclinical activities gather further momentum toward human clinical trials, and we spend a full year occupying our new office and laboratory facility, which we began to occupy in the fourth quarter of 2016.

As of June 30, 2017, the company had an accumulated deficit of $81.8 million. We expect our losses to increase as we continue to incur significant research and development and other expenses related to the advancement of our therapeutic programs and our ongoing operations. Based on our research and development plans and expectations related to the progress of the company’s programs, we expect that the cash and cash equivalents as of June 30, 2017, as well as technology access and research funding from Novartis and Regeneron, will enable Intellia to fund operating expenses and capital expenditures through mid-2019, excluding any potential milestone payments or extension fees received under our collaboration agreements with Novartis and Regeneron.

On August 1, 2017 Genomic Health, Inc. (NASDAQ: GHDX) reported financial results and business progress for the quarter ended June 30, 2017 (Press release, Genomic Health, AUG 1, 2017, View Source [SID1234519966]).

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Total revenue was $85.5 million in the second quarter of 2017, compared with $82.0 million in the second quarter of 2016, an increase of 4 percent, and an increase of 5 percent on a constant currency basis.i

U.S. product revenue was $72.4 million in the second quarter of 2017, compared with $69.6 million in the second quarter of 2016. U.S. invasive breast revenue from Oncotype DX Breast Recurrence Score test sales was $65.6 million in the second quarter of 2017, compared with $64.4 million in the second quarter of 2016. U.S. prostate revenue from Oncotype DX Genomic Prostate Score (GPS) test sales was $4.1 million in the second quarter of 2017, compared with $2.3 million in the second quarter of 2016.

International product revenue was $13.1 million in the second quarter of 2017, compared with $12.3 million in the second quarter of 2016, an increase of 6 percent, and an increase of 10 percent on a constant currency basis.i

"In the second quarter, we continued to deliver solid results reflecting both the strength and differentiation of our clinical data and unmatched commercial channel, generating a 9 percent increase in test volume and a 4 percent increase in revenue," said Kim Popovits, chairman of the board, chief executive officer and president of Genomic Health. "Importantly, we delivered operating leverage and made significant progress toward our goal of delivering full-year profitability, having improved net loss by $9 million in the first half of the year."

More than 31,550 Oncotype test results were delivered in the second quarter of 2017, an increase of 9 percent, compared with more than 29,060 test results delivered in the same period in 2016. Oncotype DX Breast Recurrence Score tests delivered in the U.S. grew 5 percent and Oncotype DX Genomic Prostate Score tests delivered in the U.S. grew 38 percent compared with the second quarter of the prior year. International tests delivered grew 12 percent compared with the same period of the prior year and represented approximately 24 percent of total test volume in the second quarter of 2017.


Operating loss for the second quarter of 2017 improved to $3.1 million, compared with $5.1 million for the second quarter of 2016. Net loss was $2.7 million, or 8 cents per share, for the second quarter of 2017, compared with a net loss of $6.1 million, or 18 cents per share, for the second quarter of 2016. Basic and diluted net loss per share was $0.08 for the second quarter of 2017, compared with basic and diluted net loss per share of $0.18 for the second quarter of 2016.

Total revenue for the six months ended June 30, 2017 was $169.5 million compared with $162.9 million for the six months ended June 30, 2016, an increase of 4 percent. On a constant currency basis, revenue increased 5 percent compared with the same period in the prior year.i

International product revenue was $26.5 million for the six months ended June 30, 2017, compared with $22.7 million for the six months ended June 30, 2016, an increase of 16 percent, and an increase of 20 percent on a constant currency basis.i

Operating loss improved to $6.0 million for the six months ended June 30, 2017 compared with an operating loss of $13.9 million for the six months ended June 30, 2016. Net loss was $3.5 million for the six months ended June 30, 2017 compared with a net loss of $12.5 million for the six months ended June 30, 2016.

Cash and cash equivalents and short-term marketable securities at June 30, 2017 were $109.8 million, compared with $87.7 million at December 31, 2016 excluding the fair value of the company’s investment in a marketable security of $9.3 million.

2017 Financial Outlook

The company is providing the following adjusted financial guidance for the full year ending December 31, 2017:

·
Total revenue of between $345 to $355 million (formerly $355 to $370 million); and
·
Profit for the full-year at either end of revenue range (formerly profit at revenue above $362.5 million).

"While the timing of important reimbursement drivers has delayed the pace of revenue growth, we expect to deliver full-year profitability at these revised revenue levels, including double-digit revenue growth in the fourth quarter," said Brad Cole, chief operating officer and chief financial officer of Genomic Health. "We expect full-year CMS intermediate prostate coverage and the implementation of both PAMA reimbursement rates and AJCC staging criteria, along with increased global market penetration, to drive strong revenue growth in 2018."

Recent Business Highlights

·
Presented new results from a large, community-based, multi-center clinical validation study conducted at Kaiser Permanente at the American Urological Association (AUA) 2017 Annual Meeting. The results confirmed that the Oncotype DX GPS test is a strong independent predictor of prostate cancer-specific death and disease progression (metastases) at 10 years in men with localized prostate cancer.
·
Data from two Oncotype DX GPS test analyses based on a prospective, multi-center, 1,200-patient study were also presented at AUA, including results that represent the first-ever prospective validation of a tissue-based molecular marker in prostate cancer. The second analysis, presented at AUA and published online in Urology, reinforced that the GPS test significantly increases use of and persistence on active surveillance.
·
Initiated an early access Clinical Utility Program for select centers around the country in preparation for the commercial launch of the Oncotype DX AR-V7 Nucleus Detect test in collaboration with Epic Sciences.
·
The 15th St. Gallen International Breast Cancer Conference Expert Panel published updated guidelines endorsing the Oncotype DX Breast Recurrence Score test for guiding treatment decisions on adjuvant chemotherapy in both node-negative and node-positive patients (up to three nodes).

·
Breast Cancer Research and Treatment published positive five-year clinical outcome results from the PlanB study led by the West German Study Group (WSG) in 93 centers across Germany. The study showed that women with Recurrence Score results of 11 or less who were treated with hormonal therapy alone had excellent outcomes with 94 percent disease-free survival rates at five years despite having high-risk disease by traditional parameters.
·
Presented results from eight studies across breast, prostate and kidney cancers that provide additional evidence of the value of Oncotype DX tests in predicting clinically meaningful endpoints and outcomes across cancer types at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago.

On August 1, 2017 Exelixis, Inc. (NASDAQ:EXEL) reported that data from clinical trials of cabozantinib and cobimetinib will be the subject of 10 presentations at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress in Madrid, September 8 – 12, 2017 (Press release, Exelixis, AUG 1, 2017, View Source [SID1234519965]).

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Progression-free survival by independent radiology review and updated overall survival results from CABOSUN, a randomized phase 2 clinical trial of cabozantinib compared with sunitinib in patients with previously untreated advanced renal cell carcinoma (RCC), will be presented as a late-breaking abstract in the Genitourinary Tumours, Non-Prostate poster discussion session on Sunday, September 10. Final data from the phase 1 study of cabozantinib in combination with nivolumab with or without ipilimumab for the treatment of metastatic urothelial carcinoma and other genitourinary malignancies will be presented in the Genitourinary Tumours, Non-Prostate oral presentation session on Saturday, September 9. Additionally, poster presentations will detail the evaluation of cabozantinib in RCC and advanced penile squamous cell carcinoma, and of cobimetinib in combination studies in metastatic melanoma.

"We look forward to this year’s ESMO (Free ESMO Whitepaper) Congress where new data from the CABOSUN trial of cabozantinib in patients with previously untreated advanced renal cell carcinoma will be presented, as well as the final analysis from the study exploring cabozantinib in combination with nivolumab and ipilimumab in genitourinary tumors, including metastatic urothelial carcinoma," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. "The slate of data featuring Exelixis-discovered compounds demonstrates our commitment to advancing our ongoing clinical research program to help improve care and outcomes for patients with cancer."

Cabozantinib to be featured in eight presentations

The full schedule of cabozantinib presentations expected at the meeting is as follows:

Oral Presentation

[846O] "Final results of a phase I study of cabozantinib (Cabo) plus nivolumab (Nivo) and CaboNivo plus Ipilimumab (Ipi) in patients (pts) with metastatic urothelial carcinoma (mUC) and other genitourinary (GU) malignancies"
Dr. Rosa Nadal, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA
Session: Genitourinary Tumours, Non-Prostate
Oral presentation Saturday, September 9, 9:15 – 10:45 a.m. CEST, Madrid Auditorium
Note: This is a National Cancer Institute Cancer Therapy Evaluation Program (NCI-CTEP) study.

Poster Discussion

[LBA38] "Progression-free survival (PFS) by independent review and updated overall survival (OS) results from Alliance A031203 trial (CABOSUN): cabozantinib versus sunitinib as initial targeted therapy for patients (pts) with metastatic renal cell carcinoma (mRCC)"
Dr. Toni Choueiri, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
Session: Genitourinary Tumours, Non-Prostate
Poster presented Sunday, September 10, 2:45 – 4:15 p.m. CEST, Cordoba Auditorium
Note: This is an NCI-CTEP study.

Poster Presentations

[872P] "Outcomes based on plasma biomarkers in METEOR, a randomized phase 3 trial of cabozantinib (C) vs everolimus (E) in advanced renal cell carcinoma (RCC)"
Dr. Thomas Powles, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London, England
Session: Genitourinary Tumours, Non-Prostate
Poster presented Sunday, September 10, 1:15 – 2:15 p.m. CEST, Hall 8

[876P] "Efficacy of cabozantinib (C) after PD-1/PD-L1 checkpoint inhibitors in metastatic renal cell carcinoma (mRCC): the Gustave Roussy experience"
Dr. Lisa Derosa, Gustave Roussy Institute of Oncology, Villejuif, France
Session: Genitourinary Tumours, Non-Prostate
Poster presented Sunday, September 10, 1:15 – 2:15 p.m. CEST, Hall 8

[891P] "Outcomes of patients with metastatic renal cell carcinoma (mRCC) who were treated with second-line (2L) vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) after first-line (1L) immune checkpoint inhibitor (ICI) therapy"
Dr. A.Y. Shah, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Session: Genitourinary Tumours, Non-Prostate
Poster presented Sunday, September 10, 1:15 – 2:15 p.m. CEST, Hall 8

[901P] "Safety and efficacy of cabozantinib for metastatic renal cell carcinoma (mRCC): real world data from an Italian Expanded Access Program (EAP)"
Dr. G. Procopio, Department of Medical Oncology, Fondazione IRCCS – Istituto Nazionale dei Tumori, Milan, Italy
Session: Genitourinary Tumours, Non-Prostate
Poster presented Sunday, September 10, 1:15 – 2:15 p.m. CEST, Hall 8

[912P] "Cabozantinib for the treatment of patients with metastatic variant histology renal cell carcinoma (vhRCC): a retrospective study"
Dr. M.T. Campbell, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Session: Genitourinary Tumours, Non-Prostate
Poster presented Sunday, September 10, 1:15 – 2:15 p.m. CEST, Hall 8

[927TiP] "Cabozantinib in patients with advanced penile squamous cell carcinoma (PSCC): the open-label, single-arm, single-center, phase 2, CaboPen trial"
Dr. A. Necchi, Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Session: Genitourinary Tumours, Non-Prostate
Poster presented Sunday, September 10, 1:15 – 2:15 p.m. CEST, Hall 8

Cobimetinib to be featured in two presentations

Also at the congress, Exelixis’ collaborator Genentech, a member of the Roche Group, will present data on cobimetinib, an Exelixis-discovered compound, in metastatic melanoma. The full schedule of cobimetinib presentations expected at the meeting is as follows:

Poster Discussion

[1225PD] "Prognostic impact of early complete metabolic response on FDG-PET, in BRAF V600 mutant metastatic melanoma patients treated with combination vemurafenib & cobimetinib"
Dr. Wen Xu, Peter MacCallum Cancer Centre, Melbourne, Australia
Session: Melanoma and Other Skin Tumours
Poster presented Monday, September 11, 11:00 a.m. – 12:15 p.m. CEST, Pamplona Auditorium

Poster Presentation

[1241P] "Impact of duration of response (DOR) on overall survival (OS) in patients with metastatic melanoma treated with dacarbazine (DTIC), vemurafenib (V), or cobimetinib plus vemurafenib (C+V): a pooled analysis"
Dr. Karl Lewis, University of Colorado Cancer Center, Aurora, Colorado, USA
Session: Melanoma and Other Skin Tumours
Poster presented Sunday, September 10, 1:15 – 2:15 p.m. CEST, Hall 8

About the CABOSUN Study

On May 23, 2016, Exelixis announced that CABOSUN met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in PFS compared with sunitinib in patients with advanced intermediate- or poor-risk RCC as determined by investigator assessment. CABOSUN was conducted by The Alliance for Clinical Trials in Oncology as part of Exelixis’ collaboration with the NCI-CTEP. These results were first presented by Dr. Toni Choueiri at the ESMO (Free ESMO Whitepaper) 2016 Congress, and published in the Journal of Clinical Oncology (Choueiri, JCO, 2016).1 In June 2017, a blinded independent radiology review committee confirmed that cabozantinib provided a clinically meaningful and statistically significant improvement in the primary efficacy endpoint of investigator-assessed PFS.

CABOSUN was a randomized, open-label, active-controlled phase 2 trial that enrolled 157 patients with advanced RCC determined to be intermediate- or poor-risk by the IMDC criteria. Patients were randomized 1:1 to receive cabozantinib (60 mg once daily) or sunitinib (50 mg once daily, 4 weeks on followed by 2 weeks off). The primary endpoint was PFS. Secondary endpoints included overall survival and objective response rate. Eligible patients were required to have locally advanced or metastatic clear-cell RCC, ECOG performance status 0-2 and had to be intermediate or poor risk per the IMDC criteria (Heng, JCO, 2009).2 Prior systemic treatment for RCC was not permitted.

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

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.3

The American Cancer Society’s 2017 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.4 Clear cell RCC is the most common type of kidney cancer in adults.5 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.6 Approximately 30,000 patients in the U.S. and 68,000 globally require treatment, and an estimated 14,000 patients in the U.S. each year are in need of a first-line treatment for advanced kidney cancer.7

Urothelial cancers encompass carcinomas of the bladder, ureter and renal pelvis at a ratio of 50:3:1, respectively.8 Urothelial carcinoma occurs mainly in older people, with 90 percent of patients aged 55 or older.9 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.9 In 2013, an estimated 587,426 people were living with bladder cancer in the U.S.10

About CABOMETYX (cabozantinib)

CABOMETYX is the tablet formulation of cabozantinib. Its targets include MET, AXL and VEGFR-1, -2 and -3. In preclinical models, cabozantinib has been shown to inhibit the activity of these receptors, which are involved in normal cellular function and pathologic processes such as tumor angiogenesis, invasiveness, metastasis and drug resistance.

CABOMETYX is available in 20 mg, 40 mg or 60 mg doses. The recommended dose is 60 mg orally, once daily.

On April 25, 2016, the FDA approved CABOMETYX tablets for the treatment of patients with advanced RCC who have received prior anti-angiogenic therapy. In February of 2016, Exelixis and Ipsen jointly announced an exclusive licensing agreement for the commercialization and further development of cabozantinib indications outside of the United States, Canada and Japan. This agreement was amended in December of 2016 to include commercialization rights for Ipsen in Canada. On September 9, 2016, the European Commission approved CABOMETYX tablets for the treatment of advanced RCC in adults who have received prior vascular endothelial growth factor (VEGF)-targeted therapy in the European Union, Norway and Iceland. Ipsen has confirmed its intent to submit the regulatory dossier for cabozantinib as a treatment for first-line advanced renal cell carcinoma in the European Union in the third quarter of 2017.

On January 30, 2017, Exelixis and Takeda Pharmaceutical Company Limited announced an exclusive licensing agreement for the commercialization and further clinical development of cabozantinib for all future indications in Japan, including RCC.

CABOMEYX is not indicated for the treatment of previously untreated advanced RCC.

U.S. Important Safety Information

Hemorrhage: Severe hemorrhage occurred with CABOMETYX. The incidence of Grade ≥3 hemorrhagic events was 2.1% in CABOMETYX-treated patients and 1.6% in everolimus-treated patients. Fatal hemorrhages also occurred in the cabozantinib clinical program. Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.

Gastrointestinal (GI) Perforations and Fistulas: Fistulas were reported in 1.2% (including 0.6% anal fistula) of CABOMETYX-treated patients and 0% of everolimus-treated patients. GI perforations were reported in 0.9% of CABOMETYX-treated patients and 0.6% of everolimus-treated patients. Fatal perforations occurred in the cabozantinib clinical program. Monitor patients for symptoms of fistulas and perforations. Discontinue CABOMETYX in patients who experience a fistula that cannot be appropriately managed or a GI perforation.

Thrombotic Events: CABOMETYX treatment results in an increased incidence of thrombotic events. Venous thromboembolism was reported in 7.3% of CABOMETYX-treated patients and 2.5% of everolimus-treated patients. Pulmonary embolism occurred in 3.9% of CABOMETYX-treated patients and 0.3% of everolimus-treated patients. Events of arterial thromboembolism were reported in 0.9% of CABOMETYX-treated patients and 0.3% of everolimus-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. Hypertension was reported in 37% (15% Grade ≥3) of CABOMETYX-treated patients and 7.1% (3.1% Grade ≥3) of everolimus-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: Diarrhea occurred in 74% of patients treated with CABOMETYX and in 28% of patients treated with everolimus. Grade 3 diarrhea occurred in 11% of CABOMETYX-treated patients and in 2% of everolimus-treated patients. 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. Dose modification due to diarrhea occurred in 26% of patients.

Palmar-Plantar Erythrodysesthesia Syndrome (PPES): Palmar-plantar erythrodysesthesia syndrome (PPES) occurred in 42% of patients treated with CABOMETYX and in 6% of patients treated with everolimus. Grade 3 PPES occurred in 8.2% of CABOMETYX-treated patients and in <1% of everolimus-treated patients. Withhold CABOMETYX in patients who develop intolerable Grade 2 PPES or Grade 3 PPES until improvement to Grade 1; resume CABOMETYX at a reduced dose. Dose modification due to PPES occurred in 16% of patients.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): 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: CABOMETYX can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the last dose.

Adverse Reactions: The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, nausea, decreased appetite, PPES, hypertension, vomiting, weight decreased, and constipation.

Drug Interactions: Strong CYP3A4 inhibitors and inducers: Reduce the dosage of CABOMETYX if concomitant use with strong CYP3A4 inhibitors cannot be avoided. Increase the dosage of CABOMETYX if concomitant use with strong CYP3A4 inducers cannot be avoided.

Lactation: Advise a lactating woman not to breastfeed during treatment with CABOMETYX and for 4 months after the final dose.

Reproductive Potential: Contraception―Advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the final dose. Infertility ―CABOMETYX may impair fertility in females and males of reproductive potential.

Hepatic Impairment: Reduce the CABOMETYX dose in patients with mild (Child-Pugh score [C-P] A) or moderate (C-P B) hepatic impairment. CABOMETYX is not recommended for use in patients with severe hepatic impairment.

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About the Cobimetinib and Vemurafenib Combination

Cobimetinib is a reversible inhibitor that blocks the activity of MEK, a protein kinase that is part of a key pathway (the RAS-RAF-MEK-ERK pathway) that promotes cell division and survival. This pathway is frequently activated in human cancers including melanoma, where mutation of one of its components (BRAF) causes abnormal activation in about 50% of cases. Tumors with BRAF mutations may develop resistance and subsequently progress after treatment with a BRAF inhibitor. About 50% of patients with BRAF mutation positive melanoma experience a tumor response when treated with a BRAF inhibitor, however development of resistance and subsequent tumor progression limits treatment benefit. Clinical and preclinical analyses indicated that reactivation of the MEK-ERK pathway may underlie development of resistance to BRAF inhibitors in many progressing tumors, and that co-treatment with a BRAF and MEK inhibitor delays the emergence of resistance in the preclinical setting, providing the rationale for testing the combination of vemurafenib and cobimetinib in clinical trials. The U.S. Food & Drug Administration approved cobimetinib for the treatment of unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in combination with vemurafenib, in 2015. Cobimetinib is also being investigated in combination with several investigational and approved medicines, including an immunotherapy, in several tumor types, including non-small cell lung cancer, colorectal cancer, triple-negative breast cancer and melanoma.