ArQule Reports First Quarter 2019 Financial Results

On May 1, 2019 ArQule, Inc. (Nasdaq: ARQL) reported its financial results for the first quarter, 2019 (Press release, ArQule, MAY 1, 2019, View Source [SID1234535491]).

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For the quarter ended March 31, 2019, the Company reported a net loss of $10,267,000, or $0.09 per share, compared with net loss of $6,532,000, or $0.07 per share, for the quarter ended March 31, 2018.

As of March 31, 2019, the Company had a total of approximately $92,223,000 in cash, cash equivalents, and marketable securities.

Key Highlights from Q1, 2019

ARQ 531, our potent and reversible dual inhibitor of both wild-type and C481S-mutant BTK. Reported in March that the first evaluable CLL patient with a C481S mutation enrolled in cohort 7 (65 mg QD) of our phase 1 trial achieved a partial response that has since been confirmed with a subsequent scan. This is in addition to a previously reported follicular lymphoma patient who had also achieved a partial response and continues on therapy. Cohort 7 has been cleared for safety and we have begun enrolling patients in cohort 8 (75 mg QD). No additional DLTs have been observed at any dose. We plan to present detailed, updated data from this ongoing trial at the European Hematological Association meeting in June
Miransertib, our potent and selective first-generation AKT inhibitor. Concluded interactions with the FDA and defined the registrational trial designs for both Proteus syndrome and PIK3CA-Related Overgrowth Spectrum (PROS). We have finalized the protocol and received the first conditional IRB approvals
ARQ 751, our highly potent and selective next-generation AKT inhibitor. Signal generation work in genetically-defined solid tumors continues, and we plan to present the final data set at a major conference by year end
Derazantinib, our FGFR inhibitor, partnered with Basilea and Sinovant, in a registrational trial for intrahepatic cholangiocarcinoma. Substantially completed the timely recruitment and transfer of clinical and other responsibilities to Sinovant and Basilea
Paolo Pucci, Chief Executive Officer of ArQule, commented, "We have made tremendous progress across our pipeline in Q1, and we are particularly pleased with the safety and dose dependent clinical activity profile that is emerging with ARQ 531."

"We are busy collecting data for our ARQ 531 presentation at EHA (Free EHA Whitepaper), and we are confident that we will demonstrate meaningful incremental clinical activity in addition to the two PRs already announced", commented Dr. Brian Schwartz, Chief Medical Officer of ArQule. "We are also pleased by the rapid review of the initial IRBs for our registrational trial with miransertib in Proteus syndrome and PROS."

Revenues and Expenses

Revenues for the first quarter, 2019, were $1,345,000 compared with revenues of $4,138,000 for the first quarter, 2018.

Research and development expenses in the first quarter, 2019 were $7,448,000 compared with $5,812,000 for the first quarter, 2018.

General and administrative expenses in the first quarter, 2019 were $4,300,000 compared with $2,351,000 for the first quarter, 2018.

2019 Financial Guidance

Our 2019 financial guidance has not changed. For 2019, ArQule expects revenue to range between $3 and $5 million. Net loss is expected to range between $40 and $43 million, and net loss per share to range between $(0.37) and $(0.39) for the year. ArQule expects to end 2019 with between $60 and $63 million in cash and marketable securities.

Conference Call and Webcast

ArQule will hold its first quarter financial results call today, May 1, 2019 at 9:00 a.m. ET. The live webcast can be accessed in the "Investors and Media" section of our website, www.arqule.com, under "Events and Presentations." You may also listen to the call by dialing (877) 868-1831 within the U.S. or (914) 495-8595 outside the U.S. A replay will be available two hours after the completion of the call and can be accessed in the "Investors and Media" section of our website, www.arqule.com, under "Events and Presentations."

Exelixis Announces First Quarter 2019 Financial Results and Provides Corporate Update

On May 1, 2019 Exelixis, Inc. (Nasdaq: EXEL) reported financial results for the first quarter of 2019 and provided an update on progress toward fulfilling its key corporate objectives, as well as commercial and clinical development milestones (Press release, Exelixis, MAY 1, 2019, View Source [SID1234535507]).

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"The first quarter of 2019 was a very productive start to the year, with strong execution across all aspects of our business," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. "We continued our efforts to maximize the commercial and clinical potential of cabozantinib through the U.S. launch in advanced hepatocellular cancer in January, as well as the initiation of the COSMIC-313 study announced today."

Dr. Morrissey continued: "The financial stability provided by our growing revenue base across product and collaboration revenue provides Exelixis with an effective foundation upon which to pursue long-term growth. We have ambitious plans for the rest of 2019: we intend to start additional cabozantinib pivotal trials, bring new assets into our development organization through internal drug discovery and external business development, and advance our early-stage pipeline, including XL092. As we move through our 25th anniversary year, not only is our commitment to helping patients with cancer stronger than ever, but our ability to do so is notably stronger as well."

First Quarter 2019 Financial Results

Total revenues for the quarter ended March 31, 2019 were $215.5 million, compared to $213.7 million for the comparable period in 2018.

Total revenues included net product revenues of $179.6 million for the quarter ended March 31, 2019, compared to $134.3 million for the comparable period in 2018. The increase in net product revenues reflected the continued growth of CABOMETYX (cabozantinib) in the U.S. for the treatment of patients with advanced renal cell carcinoma (RCC), as well as the U.S. launch of CABOMETYX for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib, following its approval by the U.S. Food and Drug Administration (FDA) in January 2019.

CABOMETYX net product revenues for the quarter ended March 31, 2019 were $175.9 million, compared to $171.6 million for the quarter ended December 31, 2018. CABOMETYX net product revenues, as compared to the preceding quarter, were impacted by higher discounts and allowances of $7.2 million, driven by increased uptake in the government payor channel. In addition, as of March 31, 2019, the quantity of CABOMETYX inventory in the U.S. wholesaler distribution channel was approximately $2.3 million lower than it was as of December 31, 2018.

Total revenues for the quarter ended March 31, 2019 also include collaboration revenues of $35.9 million, compared to $79.4 million for the comparable period in 2018. The decrease in collaboration revenues was primarily the result of a decrease in revenues from milestones recognized from Exelixis’ collaboration agreements, which was partially offset by increases in royalty revenues on net sales of cabozantinib by Ipsen Pharma SAS (Ipsen) outside of the U.S. and Japan, and development cost reimbursements by Ipsen and Takeda Pharmaceutical Company Ltd. (Takeda).

Research and development expenses for the quarter ended March 31, 2019 were $63.3 million, compared to $37.8 million for the comparable period in 2018. The increase in research and development expenses was primarily related to increases in clinical trial costs, personnel expenses and stock-based compensation. The increase in clinical trial costs was primarily due to costs associated with the expanding clinical trial program for cabozantinib that now includes four phase 3 pivotal studies (CheckMate 9ER, COSMIC-311, COSMIC-312 and COSMIC-313), as well as the multi-cohort phase 1b study, COSMIC-021. The increases in personnel expenses and stock-based compensation were primarily due to increases in headcount to support Exelixis’ expanded discovery and development efforts.

Selling, general and administrative expenses for the quarter ended March 31, 2019 were $60.1 million, compared to $54.0 million for the comparable period in 2018. The increase in selling, general and administrative expenses was primarily related to increases in consulting and outside services, personnel expenses, marketing costs and stock-based compensation. The increases in personnel expenses and stock-based compensation were primarily due to increases in general and administrative headcount to support the company’s commercial and research and development organizations. The increase in consulting and outside services and marketing expenses was primarily due to increases in marketing activities in support of the CABOMETYX launch in HCC and continued support of the product in an increasingly competitive RCC market.

Provision for income taxes for the quarter ended March 31, 2019 was $14.9 million and Exelixis’ effective tax rate was 16.4%, compared to $2.5 million and 2.1%, respectively, for the comparable period in 2018. The provision for income taxes relating to Exelixis’ pre-tax income for the three months ended March 31, 2018 was largely offset by a valuation allowance against its net operating loss carryforwards and other deferred tax assets. At December 31, 2018, Exelixis released substantially all of the remaining valuation allowance against Exelixis’ deferred tax assets, after Exelixis determined that it was more likely than not that these deferred tax assets would be realized.

GAAP net income for the quarter ended March 31, 2019 was $75.8 million, or $0.25 per share, basic and $0.24 per share, diluted, compared to GAAP net income of $115.9 million, or $0.39 per share, basic and $0.37 per share, diluted, for the comparable period in 2018. The decrease in net income was primarily related to the decrease in milestone-related revenues and the increases in research and development expenses, selling, general and administrative expenses and the provision for income taxes; those changes were partially offset by the increases in net product revenues and royalty revenues recognized from Exelixis’ collaboration agreements.

Non-GAAP net income for the quarter ended March 31, 2019 was $85.5 million, or $0.28 per share, basic and $0.27 per share, diluted, compared to non-GAAP net income of $125.0 million, or $0.42 per share, basic and $0.40 per share, diluted, for the comparable period in 2018. Non-GAAP net income excludes stock-based compensation and adjusts for the related income tax effect.

Cash and cash equivalents, short- and long-term investments and long-term restricted cash and investments totaled $1,019.4 million at March 31, 2019, compared to $851.6 million at December 31, 2018.

Non-GAAP Financial Measures

To supplement Exelixis’ financial results presented in accordance with GAAP, Exelixis uses certain non-GAAP financial measures in this press release. In particular, Exelixis presents non-GAAP net income (and the related per share measures), which exclude from GAAP net income (and the related per share measures) stock-based compensation expense and adjust for the related income tax effect of this non-GAAP adjustment.

Exelixis believes that the presentation of these non-GAAP financial measures provides useful supplementary information to, and facilitates additional analysis by, investors. In particular, Exelixis believes that each of these non-GAAP financial measures, when considered together with its financial information prepared in accordance with GAAP, can enhance investors’ and analysts’ ability to meaningfully compare Exelixis’ results from period to period, and to identify operating trends in Exelixis’ business. Exelixis has excluded stock-based compensation expense because it is a non-cash expense that may vary significantly from period to period as a result of changes not directly or immediately related to the operational performance for the periods presented. Exelixis also regularly uses these non-GAAP financial measures internally to understand, manage and evaluate its business and to make operating decisions.

These non-GAAP financial measures are in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP. Exelixis encourages investors to carefully consider its results under GAAP, as well as its supplemental non-GAAP financial information and the reconciliation between these presentations, to more fully understand Exelixis’ business. Reconciliations between GAAP and non-GAAP results are presented in the tables of this release.

2019 Financial Guidance

Exelixis is maintaining the following financial guidance for 2019. Cost of goods sold is expected to be between 4% and 5% of net product revenues. Research and development expenses are expected to be between $285 million and $315 million and include non-cash expenses related to stock-based compensation of $20 million. Selling, general and administrative expenses are expected to be between $220 million and $240 million and include non-cash expenses related to stock-based compensation of $35 million. Guidance for the effective tax rate in 2019 is between 21% and 23%.

Cabozantinib Highlights

Strong Growth in Cabozantinib Franchise Net Revenues and Royalties. Net product revenues generated by the cabozantinib franchise were $179.6 million during the quarter ended March 31, 2019, an increase of 34% year-over-year. During the first quarter of 2019, CABOMETYX generated $175.9 million in net product revenues and COMETRIQ (cabozantinib) capsules for the treatment of patients with progressive, metastatic medullary thyroid cancer generated an additional $3.7 million in net product revenues. Based upon our partner Ipsen’s cabozantinib-related revenues in the first quarter of 2019 of approximately $63 million, Exelixis earned $14.0 million in royalty revenues at the 22% royalty rate. CABOMETYX continues to expand its global footprint, where it is currently approved and commercially available in 41 and 28 countries, respectively.

FDA Approval of CABOMETYX Tablets for Previously Treated HCC. In January, Exelixis announced the FDA approval of CABOMETYX for the treatment of patients with HCC who have been previously treated with sorafenib. The FDA’s approval of CABOMETYX was based on results from the CELESTIAL phase 3 pivotal trial.

Cabozantinib Data at the 2019 American Society for Clinical Oncology Gastrointestinal Cancers Symposium (ASCO-GI). In January, data from clinical trials of cabozantinib were featured in five presentations at ASCO (Free ASCO Whitepaper)-GI in San Francisco, including further analyses from the CELESTIAL trial.

Takeda’s Application to the Japanese Ministry of Health, Labour and Welfare (MHLW) for CABOMETYX as a Treatment for Advanced RCC. In April, Takeda, Exelixis’ partner in cabozantinib’s development and commercialization in Japan, announced that it applied to the Japanese MHLW for approval to manufacture and sell CABOMETYX as a treatment for unresectable and metastatic RCC in Japan. Per the terms of the exclusive licensing agreement the two companies entered into in 2017, Exelixis will receive a $10.0 million milestone payment as a result of this regulatory filing. Exelixis is eligible for additional development, regulatory and first-sales milestone payments, as well as royalties on sales of cabozantinib in Japan.

Completion of Enrollment in CheckMate 9ER. In April, CheckMate 9ER, the phase 3 pivotal trial evaluating the combination of cabozantinib and nivolumab versus sunitinib in patients with previously untreated advanced or metastatic RCC completed enrollment, including in Japan where the last few patients are in the process of being randomized. CheckMate 9ER is sponsored by Bristol-Myers Squibb Company (BMS) and co-funded by Exelixis, and Exelixis’ partners Ipsen and Takeda.

Initiation of COSMIC-313, Phase 3 Pivotal Trial Evaluating the Triplet Combination of Cabozantinib, Nivolumab and Ipilimumab Versus the Combination of Nivolumab and Ipilimumab in Patients with Previously Untreated Advanced Intermediate- or Poor-Risk RCC. Today, Exelixis announced the initiation of COSMIC-313, a multicenter, randomized, double-blinded, controlled phase 3 pivotal trial that aims to enroll approximately 676 patients at 150 sites globally. The primary endpoint of the trial is progression-free survival, and the secondary endpoints are overall survival and objective response rate. COSMIC-313 will be conducted in collaboration with BMS, which is providing nivolumab and ipilimumab for use in this trial.

Corporate Highlights

MINNEBRO Receives Regulatory Approval for the Treatment of Hypertension in Japan. In January, Exelixis’ partner Daiichi Sankyo Company, Limited (Daiichi Sankyo) announced that MINNEBRO (esaxerenone) tablets had received approval from the Japanese MHLW as a treatment for patients with hypertension. MINNEBRO is a compound identified during the prior research collaboration between Exelixis and Daiichi Sankyo, which the companies entered into in March 2006, and has been subsequently developed by Daiichi Sankyo. Per the collaboration agreement, Exelixis will receive a $20.0 million milestone payment upon the first commercial sale of MINNEBRO in Japan. Exelixis is eligible for additional commercialization milestone payments, as well as low double-digit royalties on sales of MINNEBRO.

Start of Phase 1 Development for XL092. In February, Exelixis announced it had submitted an investigational new drug (IND) application to the FDA for XL092, a next-generation small molecule tyrosine kinase inhibitor targeting VEGF receptors, MET and other kinases implicated in cancer’s growth and spread. Following the FDA’s acceptance of the IND filing, Exelixis initiated a phase 1 dose escalation trial evaluating the pharmacokinetics, safety and tolerability of XL092 in patients with advanced solid tumors, with the primary objective of determining a dose for daily oral administration of XL092 suitable for further evaluation. Assuming positive data from the initial phase of the trial, the expansion phase is designed to further explore the selected dose of XL092 in individual tumor cohorts, where safety, tolerability and initial clinical activity would be evaluated. XL092 is the first clinical candidate to emerge from Exelixis’ in-house laboratories since Exelixis resumed drug discovery activities.

Basis of Presentation

Exelixis has adopted a 52- or 53-week fiscal year that generally ends on the Friday closest to December 31st. For convenience, references in this press release as of and for the fiscal periods ended March 29, 2019, December 28, 2018 and March 30, 2018 are indicated as being as of and for the periods ended March 31, 2019, December 31, 2018 and March 31, 2018, respectively.

Conference Call and Webcast

Exelixis management will discuss the company’s financial results for the first quarter of 2019 and provide a general business update during a conference call beginning at 5:00 p.m. EDT / 2:00 p.m. PDT today, Wednesday, May 1, 2019.

To access the webcast link, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company’s website at least 15 minutes prior to the conference call to ensure adequate time for any software download that may be required to listen to the webcast. Alternatively, please call 855-793-2457 (domestic) or 631-485-4921 (international) and provide the conference call passcode 4774486 to join by phone.

A telephone replay will be available until 8:00 p.m. EDT on May 3, 2019. Access numbers for the telephone replay are: 855-859-2056 (domestic) and 404-537-3406 (international); the passcode is 4774486. A webcast replay will also be archived on www.exelixis.com for one year.

Operational Update

On May 1, 2019 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a biotechnology company developing novel immunotherapy treatments for cancer and autoimmune diseases, reported an update for the ongoing development of its product candidates (Press release, Immutep, MAY 1, 2019, View Source [SID1234535559]).

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Efti Clinical Update

AIPAC – Phase IIb Clinical Trial

To date, there have been 211 patients enrolled in the Company’s Phase IIb AIPAC clinical trial, which is evaluating eftilagimod alpha ("efti" or "IMP321") in combination with paclitaxel, a chemotherapy, in metastatic breast cancer. Full recruitment of the trial, 226 patients, is expected to occur in the second quarter of this year. The trial is being conducted at 33 clinical trial sites across Germany, the UK, France, Hungary, Belgium, Poland and the Netherlands.

The first read out of Progression Free Survival (PFS) data is expected within the next 11 months, but not before Q4 2019, depending on the number of predefined progression events. Other endpoints include Overall Response Rate (ORR) and Overall Survival (OS).

TACTI-002 – Phase II Clinical Trial

15 patients have been enrolled in Immutep’s Phase II TACTI-002 clinical trial across seven clinical sites in the U.S., Europe and Australia. This figure includes 11 patients in the first line non-small cell lung cancer (NSCLC) cohort, which requires 17 patients to complete recruitment of this initial cohort.

The TACTI-002 study is being conducted in collaboration with Merck & Co., Inc., Kenilworth, NJ, USA (known as "MSD" outside the United States and Canada) and is evaluating the combination of efti with MSD’s KEYTRUDA (or pembrolizumab, an anti-PD-1 therapy) in up to 109 patients with second line head and neck squamous cell carcinoma or NSCLC in first and second line.

Patient recruitment is ongoing and Immutep expects to report first data from the study in mid-2019.

LOGO

TACTI-mel – Phase I Clinical Trial

Immutep reported positive, more mature data from its ongoing and fully recruited TACTI-mel Phase I clinical study in melanoma in March. The trial is evaluating the combination of efti with anti-PD-1 therapy KEYTRUDA (pembrolizumab) in 24 patients with unresectable or metastatic melanoma.

Key findings from the ongoing trial were as follows:


Part A (starting cycle 5 of

pembrolizumab therapy) N=18


Part B (starting day 1 cycle 1 of

pembrolizumab therapy) N=6

Overall Response Rate (ORR)

33% (61%*) 50%
Disease Control Rate (DCR)

66% 66%
*Exploratory ORR when tumour size is measured according to irRC from day 1 of cycle 1 of pembrolizumab and following combination therapy (which starts at cycle 5 of prembrolizumab treatment).

In addition, efti continues to have a very favorable safety profile in doses up to 30 mg administered s.c. every 2 weeks. The data was presented at the World Immunotherapy Congress 2019.

INSIGHT & INSIGHT-004 – Phase I Clinical Trials

INSIGHT-004 is a Phase I clinical trial in collaboration with Merck KGaA, Darmstadt, Germany and Pfizer Inc. and the Institute of Clinical Cancer Research, Krankenhaus Nordwest GmbH (IKF) which is evaluating the combination of efti with avelumab, a human anti-PD-L1 antibody, in patients with advanced solid malignancies. The trial protocol has now been approved by the competent authority and ethics committee and Immutep expects the first patient to be recruited in Q2 2019.

This study is taking place as an extension to the INSIGHT trial, an investigator sponsored explorative trial which is already underway and being run by our partner, IKF.

13 patients are now enrolled in the INSIGHT clinical trial, which is evaluating the potential of efti in different settings in terms of route of administration and indications.

IMP761 Update

IMP761—Preclinical Results

Immutep reported positive results from its preclinical study of IMP761, a novel LAG-3 agonist antibody being developed for the treatment of autoimmune diseases, in March. The preclinical results showed that IMP761 decreases inflammation at the tissue site, demonstrating its potential as a new therapy that could treat the cause of autoimmune disease, rather than just the symptoms.

Specifically, in vitro results showed that IMP761 caused the down-regulation of human T cell proliferation and activation. In addition, the in vivo studies showed that IMP761 causes down-modulation of T cell infiltration in a non-human-primate animal model. These results were presented at the 14th Congress of European Crohn’s and Colitis Organisation (ECCO) Conference.

The Company is continuing cell line development and GMP manufacturing preparations for IMP761 to progress the antibody towards clinical development.

Update on programs fully funded by Immutep’s licensing partners

GlaxoSmithKline – GSK2831781 / IMP731

GlaxoSmithKline (GSK) has announced that it will be pursuing a proof-of-concept study in ulcerative colitis for GSK2831781, which is derived from Immutep’s IMP731 antibody. This Phase II clinical study is expected to commence shortly.

Novartis—LAG525 / IMP701

Novartis is continuing its clinical development program for LAG525, or IMP701, in oncology. Currently, there are five ongoing Phase I/II clinical trials evaluating this product candidate.

CYTLIMIC—efti

Immutep is working with CYTLIMIC to prepare for CYTLIMIC’s clinical trials to evaluate efti as part of a therapeutic cancer vaccine, called CYT001. The vaccine contains cancer antigens to boost a patient’s own immune cells to recognise and kill cancer cells related to the antigens.

Eddingpharm (EOC Pharma)—efti

Immutep’s partner and Chinese licensee, EOC Pharma, is continuing the recruitment of patients for its Phase I clinical study of efti for the treatment of metastatic breast cancer. Immutep expects further progress from EOC Pharma later in 2019.

CRISPR Therapeutics to Participate in Upcoming Investor Conferences

On May 1, 2019 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported that members of its senior management team are scheduled to participate in the following investor conferences later this month (Press release, CRISPR Therapeutics, MAY 1, 2019, View Source [SID1234535492]):

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SunTrust Robinson Humphrey 5th Annual Life Sciences Summit
Date: Wednesday, May 8, 2019
Location: New York, NY

Bank of America Merrill Lynch 2019 Health Care Conference
Date: Wednesday, May 15, 2019
Presentation: 1:00 p.m. PT
Location: Las Vegas, NV

UBS Global Healthcare Conference
Date: Tuesday, May 21, 2019
Presentation: 11:00 a.m. ET
Location: New York, NY

A live webcast of the Bank of America Merrill Lynch and UBS events will be available on the "Events & Presentations" page in the Investors section of the Company’s website at View Source A replay of the webcasts will be archived on the Company’s website for 14 days following each presentation.

Exelixis Initiating Phase 3 Pivotal Trial (COSMIC-313) of Cabozantinib in Combination with Nivolumab and Ipilimumab Versus Nivolumab and Ipilimumab in Previously Untreated Advanced Renal Cell Carcinoma

On May 1, 2019 Exelixis, Inc. (NASDAQ: EXEL) reported that it is initiating COSMIC-313, a phase 3 pivotal trial of cabozantinib (CABOMETYX) in combination with nivolumab (Opdivo) and ipilimumab (Yervoy) versus nivolumab and ipilimumab in patients with previously untreated advanced renal cell carcinoma (RCC) with intermediate- or poor-risk disease per the International Metastatic Renal Cell Carcinoma Database Consortium (Press release, Exelixis, MAY 1, 2019, View Source [SID1234535508]). The primary endpoint of the trial is progression-free survival, and the secondary endpoints are overall survival and objective response rate.

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"Clinical observations suggest cabozantinib promotes an immune-permissive environment, which could present an opportunity for additive or synergistic effects with immune checkpoint inhibitors," said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. "The mechanisms of action of single agent cabozantinib and the combination of nivolumab and ipilimumab are complementary, and each has demonstrated efficacy in advanced renal cell carcinoma. The further combination of these agents as a triplet regimen may offer promise to previously untreated patients with intermediate- or poor-risk disease, who are known to have poor treatment outcomes."

COSMIC-313 is a multicenter, randomized, double-blinded, controlled phase 3 pivotal trial that aims to enroll approximately 676 patients at 150 sites globally. Patients will be randomized 1:1 to the experimental arm of cabozantinib in combination with nivolumab and ipilimumab and to the control arm of nivolumab and ipilimumab in combination with matched placebo.

Design of this phase 3 pivotal trial was informed by results from the ongoing phase 1b study of cabozantinib plus nivolumab with or without ipilimumab in patients with previously treated advanced genitourinary cancers, including RCC. The phase 1b trial is being conducted by the U.S. National Cancer Institute and includes centers from its Experimental Therapeutics Clinical Trials Network.

Bristol-Myers Squibb is providing nivolumab and ipilimumab for use in this trial.

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

About RCC

The American Cancer Society’s 2019 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.1 Clear cell RCC is the most common type of kidney cancer in adults.2 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.1 Approximately 32,000 patients in the U.S. and 70,000 globally require treatment, and an estimated 15,000 patients in the U.S. each year are in need of a first-line treatment for advanced kidney cancer.3

The majority of clear cell RCC tumors have lower than normal levels of a protein called von Hippel-Lindau, which leads to higher levels of MET, AXL and VEGF.4,5 These proteins promote tumor angiogenesis (blood vessel growth), growth, invasiveness and metastasis.6,7,8,9 MET and AXL may provide escape pathways that drive resistance to VEGF receptor inhibitors.5,6

About CABOMETYX (cabozantinib)

In the U.S., CABOMETYX tablets are approved for the treatment of patients with advanced RCC and for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. CABOMETYX tablets have also received regulatory approvals in the European Union and additional countries and regions worldwide. 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.

The combination of CABOMETYX with nivolumab and ipilimumab is not indicated for previously untreated advanced RCC.

U.S. Important Safety Information

Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.
Perforations and Fistulas: GastrointestinaI (GI) perforations, including fatal cases, occurred in 1% of CABOMETYX patients. Fistulas, including fatal cases, occurred in 1% of CABOMETYX patients. Monitor patients for signs and symptoms of perforations and fistulas, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a fistula that cannot be appropriately managed or a GI perforation.
Thrombotic Events: CABOMETYX increased the risk of thrombotic events. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events occurred in CABOMETYX patients. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic event requiring medical intervention.
Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension occurred in 36% (17% Grade 3 and <1% Grade 4) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy or for hypertensive crisis.
Diarrhea: Diarrhea occurred in 63% of CABOMETYX patients. Grade 3 diarrhea occurred in 11% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 diarrhea, Grade 3 diarrhea that cannot be managed with standard antidiarrheal treatments, or Grade 4 diarrhea.
Palmar-Plantar Erythrodysesthesia (PPE): PPE occurred in 44% of CABOMETYX patients. Grade 3 PPE occurred in 13% of CABOMETYX patients. Withhold CABOMETYX until improvement to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.
Proteinuria: Proteinuria occurred in 7% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. Discontinue CABOMETYX in patients who develop nephrotic syndrome.
Osteonecrosis of the Jaw (ONJ): ONJ occurred in <1% of CABOMETYX patients. ONJ can manifest as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration or erosion, persistent jaw pain, or slow healing of the mouth or jaw after dental surgery. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 28 days prior to scheduled dental surgery or invasive dental procedures. Withhold CABOMETYX for development of ONJ until complete resolution.
Wound Complications: Wound complications were reported with CABOMETYX. Stop CABOMETYX at least 28 days prior to scheduled surgery. Resume CABOMETYX after surgery based on clinical judgment of adequate wound healing. Withhold CABOMETYX in patients with dehiscence or wound healing complications requiring medical intervention.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, can occur with CABOMETYX. Evaluate for RPLS in patients 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. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to initiating CABOMETYX and advise them to use effective contraception during treatment and for 4 months after the last dose.
Adverse Reactions: The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, decreased appetite, PPE, nausea, hypertension, and vomiting.
Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.
Strong CYP3A4 Inducers: If coadministration with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.
Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.
Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. CABOMETYX is not recommended for use in patients with severe hepatic impairment.