SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Apr. 20, 2016-- Exelixis, Inc. (NASDAQ: EXEL) today announced that new data for cabozantinib, cobimetinib and XL888 will be presented at the upcoming 2016 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, June 3 – 7, 2016.

An oral presentation will include pivotal overall survival data from the METEOR study, the randomized phase 3 trial of cabozantinib versus everolimus in patients with previously treated advanced renal cell carcinoma (RCC). These data were submitted to the U.S. Food and Drug Administration (FDA) in the New Drug Application (NDA) for cabozantinib for patients with advanced RCC who have received one prior therapy. On January 28, 2016Exelixis announced that the FDA accepted the NDA for cabozantinib. The FDA granted Priority Review to the filing and assigned a Prescription Drug User Fee Act action date of June 22, 2016. Additional presentations at ASCO will highlight results from early and mid-stage trials of cabozantinib in other disease settings, including metastatic colorectal cancer, endometrial cancer and metastatic urothelial carcinomas.

“The overall survival data for cabozantinib from the METEOR trial represent an important milestone in the treatment of advanced renal cell carcinoma,” said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. “When taken alongside data from the trial’s other endpoints, this result makes cabozantinib the first therapy to demonstrate improvements in the three key measures of efficacy in a large randomized phase 3 trial of patients with this advanced form of cancer. Exelixis is committed to ongoing clinical research for patients who need new treatment options, and the slate of data for Exelixis-discovered compounds at this year’s ASCO Annual Meeting speaks to the urgency with which we and our collaborators are working to improve care and outcomes for patients with cancer.”

Cabozantinib will be the subject of nine presentations. The full schedule of cabozantinib presentations expected at the meeting is as follows (all times are in Central Daylight Time):

Oral Presentations:
[4506] “Overall survival (OS) in METEOR, a randomized phase 3 trial of cabozantinib (Cabo) versus everolimus (Eve) in patients (pts) with advanced renal cell carcinoma (RCC).”
Dr. Toni K. Choueiri, Dana Farber Cancer Institute, Boston, Massachusetts
Oral Abstract Session: Genitourinary (Nonprostate) Cancer: 8 – 11 a.m.
Sunday, June 5, 10:12 – 10:24 a.m.

Poster Presentations
[9068] “MDM2 amplification (Amp) to mediate cabozantinib resistance in patients (Pts) with advanced RET-rearranged lung cancers.”
Romel Somwar, Memorial Sloan Kettering Cancer Center, New York, New York
Poster Session: Lung Cancer—Non-Small Cell Metastatic
Poster presented Saturday, June 4, 8 – 11:30 a.m., Hall A (Poster #391)
Note: This is an Investigator-Sponsored Trial.

[3548] “Phase Ib study of cabozantinib plus panitumumab in KRAS wild-type (WT) metastatic colorectal cancer (mCRC).”
Dr. John Strickler, Duke University Medical Center, Durham, North Carolina
Poster Session: Gastrointestinal (Colorectal) Cancer
Poster presented Saturday, June 4, 8 – 11:30 a.m., Hall A (Poster #245)
Note: This is an Investigator-Sponsored Trial.

[2565] “Population pharmacokinetic (PopPK) and exposure-response (ER) modeling of cabozantinib (C) in patients (pts) with renal cell carcinoma (RCC) in the phase 3 METEOR study.”
Dr. Steve Lacy, Exelixis, Inc., South San Francisco, California
Poster Session: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics
Poster presented Sunday, June 5, 8 – 11:30 a.m., Hall A (Poster #265)

[1093] “Effect of cabozantinib treatment on circulating immune cell populations in patients with metastatic triple-negative breast cancer (TNBC).”
Dr. Dan G. Duda, Massachusetts General Hospital, Boston. Massachusetts
Poster Session: Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy
Poster presented Sunday, June 5, 8 – 11:30 a.m., Hall A (Poster #198)
Note: This is an Investigator-Sponsored Trial.

[4534] “A phase II study of cabozantinib in patients (pts) with relapsed or refractory metastatic urothelial carcinoma (mUC).”
Dr. Andrea Borghese Apolo, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Washington, D.C.
Poster Discussion Session: Genitourinary (Nonprostate) Cancer
Poster presented Monday, June 6, 1 – 4:30 p.m., Hall A; discussed at 4:45 – 6 p.m. in Arie Crown Theater
Note: This is a National Cancer Institute Cancer Therapy Evaluation Program (NCI-CTEP) study.

[4558] “Efficacy of cabozantinib (C) vs everolimus (E) in patients (pts) with advanced renal cell carcinoma (RCC) and bone metastases (mets) from the phase III METEOR study.”
Dr. Bernard Escudier, Institut Gustave Roussy, Villejuif, France
Poster Session: Genitourinary (Nonprostate) Cancer
Poster presented, Monday, June 6, 1 – 4:30 p.m., Hall A (Poster #180)

[4557] “Outcomes based on prior VEGFR TKI and PD-1 checkpoint inhibitor therapy 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, Queen Mary University, London, England
Poster Session: Genitourinary (Nonprostate) Cancer
Poster Presented Monday, June 6, 1 – 4:30 p.m., Hall A (Poster #179)

[5586] “Phase II study of cabozantinib in recurrent/metastatic endometrial cancer (EC): a study of the Princess Margaret, Chicago and California Phase II Consortia.”
Dr. Neesha Dhani, Princess Margaret Cancer Centre, University Health Network, Chicago, Illinois
Poster Session: Gynecologic Cancer
Poster Presented Monday, June 6, 1 – 4:30 p.m., Hall A (Poster #409)
Note: This is an NCI-CTEP study.

Investor/Analyst Briefing to Review Cabozantinib Data

Exelixis will host a live investor/analyst briefing on Sunday, June 5, 2016, from 7:30-9:30 p.m. EDT / 6:30-8:30 p.m. CDT / 4:30-6:30 p.m. PDT. During the briefing, Exelixis management and invited guest speakers will review and provide context for cabozantinib data presented at the ASCO Annual Meeting. The briefing will be webcasted. To access the webcast, log onto www.exelixis.com and proceed to the Event Calendar page under Investors & Media. Please connect to the company’s website at least 15 minutes prior to the webcast to ensure adequate time for any software download that may be required to listen to the webcast. An archived replay of the webcast will be available on the Event Calendar page under Investors & Media at www.exelixis.com for one year. A telephone replay of the webcast will be available until 11:59 p.m. EDT on June 7, 2016; please visit the Event Calendar page for details on phone replay access when available.

XL888 Data to be Presented in a Poster
In addition, investigational compound XL888 will be the subject of the following poster presentation (in Central Daylight Time):

[9544] “Phase I study of vemurafenib and heat shock protein 90 (HSP90) inhibitor XL888 in metastatic BRAF V600 mutant melanoma.”
Dr. Zeynep Eroglu, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida
Poster Session: Melanoma/Skin Cancers
Poster presented Saturday, June 4, 1 – 4:30 p.m., Hall A (Poster #149)
Note: This is an Investigator-Sponsored Trial.

Cobimetinib to be Featured in Eight Presentations
Also at the meeting, Exelixis’ collaborator Genentech, a member of the Roche Group, will present data on cobimetinib, an Exelixis-discovered compound, in disease settings including colorectal cancer, triple-negative breast cancer, and BRAF-mutant melanoma. The full schedule of cobimetinib presentations expected at the meeting is as follows (all times are in Central Daylight Time):

Oral Presentation:
[3502] “Clinical activity and safety of cobimetinib (cobi) and atezolizumab in colorectal cancer (CRC).”
Dr. Johanna Bendell, Sarah Cannon Research Institute, Nashville, Tennessee
Oral Abstract Session: Gastrointestinal (Colorectal) Cancer
Oral presentation on Sunday, June 5, 8 – 11 a.m., Hall B1 (abstract scheduled for 8:24 – 8:36 a.m.)

Poster Discussion:
[9510] Extended follow-up results of a phase 1B study (BRIM7) of cobimetinib and vemurafenib in BRAF-mutant melanoma
Dr. Adil Daud, University of California, San Francisco, San Francisco, California
Poster Session: Melanoma/Skin Cancers
Poster presentation from Saturday, June 4, 1 – 4:30 p.m. (Poster #115) in Hall A; discussion on Saturday, June 4, 4:45 – 6 p.m. in room E354b

Poster Presentations:
[9528] “Clinical predictors of response for coBRIM, a phase 3 study of cobimetinib (C) in combination with vemurafenib (V) in advanced BRAF-mutated melanoma (MM).”
Dr. James Larkin, The Royal Marsden Hospital, London, UK
Poster Session: Melanoma/Skin Cancers
Saturday, June 4, 1 – 4:30 p.m., Hall A (Poster #133)

[9530] “Efficacy of cobimetinib (C) and vemurafenib (V) in advanced BRAF-mutated melanoma patients (pts) with poor and favorable prognosis in the coBRIM phase 3 study.”
Dr. Grant A McArthur, Peter MacCallum Cancer Centre, East Melbourne, Australia and University of Melbourne, Parkville, Australia
Poster Session: Melanoma/Skin Cancers
Saturday, June 4, 1 – 4:30 p.m., Hall A (Poster #135)

[9533] “Adverse event (AE) incidence rates with cobimetinib (C) plus vemurafenib (V) treatment: extended follow-up (f/u) of the phase 3 coBRIM study.”
Dr. Brigitte Dréno, Nantes University, Nantes, France
Poster Session: Melanoma/Skin Cancers
Saturday, June 4, 1 – 4:30 p.m., Hall A (Poster #138)

[9536] “Identifying prognostic subgroups for outcomes in BRAFV600-mutated metastatic melanoma patients (pts) treated with vemurafenib (V) ± cobimetinib (C): A pooled analysis of BRIM-2, BRIM-3, BRIM-7 and coBRIM.”
Dr. James Larkin, The Royal Marsden Hospital, London, UK
Poster Session: Melanoma/Skin Cancers
Saturday, June 4, 1 – 4:30 p.m., Hall A (Poster #141)

[1074] “Cobimetinib (C) + paclitaxel (P) as first-line treatment in patients (pts) with advanced triple-negative breast cancer (TNBC): updated results and biomarker data from the phase 2 COLET study.”
Dr. Adam Brufsky, NRG Oncology/NSABP and Magee Women's Hospital, Pittsburgh, PA
Poster Session: Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy
Sunday, June 5, 8 – 11:30 a.m., Hall A (Poster #179)

[TPS1100] “COLET (NCT02322814): A multistage, phase 2 study evaluating the safety and efficacy of cobimetinib (C) in combination with paclitaxel (P) as first- line treatment for patients (pts) with metastatic triple-negative breast cancer (TNBC).”
Dr. David Miles, Mount Vernon Cancer Centre, London, UK
Poster Session: Breast Cancer —Triple-Negative/Cytotoxics/Local Therapy
Sunday, June 5, 8 – 11:30 a.m., Hall A (Poster #203a)

About the METEOR Phase 3 Pivotal Trial

METEOR is an open-label, event-driven trial with the primary endpoint of progression-free survival (PFS). The target enrollment for METEOR was 650 patients, and 658 patients were ultimately randomized. The trial was conducted at approximately 200 sites in 26 countries, and enrollment was weighted toward Western Europe, North America, and Australia. Patients were randomized 1:1 to receive 60 mg of cabozantinib daily or 10 mg of everolimus daily, and were stratified based on the number of prior VEGF receptor TKI therapies received, and on commonly applied RCC risk criteria developed by Motzer et al. No cross-over was allowed between the study arms.

Secondary endpoints for METEOR include overall survival (OS) and objective response rate. The secondary endpoint of OS assumed a median of 15 months for the everolimus arm and 20 months for the cabozantinib arm. The study was designed to observe 408 deaths in the entire intent-to-treat population of 650 planned patients, providing 80% power to detect a HR of 0.75. An interim analysis of OS at the 2-sided 0.0019 level employing a Lan-DeMets O’Brien-Fleming alpha-spending function was planned at the time of the primary analysis for PFS, if the trial met the primary PFS endpoint. This analysis showed a strong trend in OS favoring cabozantinib (HR=0.67, 95% CI 0.51-0.89, p=0.005), although the p-value of 0.0019 to achieve statistical significance was not reached at that time. Based upon these results and after consulting with the FDA and EMA, a second interim analysis was undertaken; the results of this second interim analysis crossed the boundary for early declaration of statistical significance.

About Advanced Renal Cell Carcinoma

The American Cancer Society’s 2016 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 17,000 patients in the U.S. and 37,000 globally require second-line or later treatment.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.^6-9 MET and AXL may provide escape pathways that drive resistance to VEGF receptor inhibitors.^5,6

About Cabozantinib

Cabozantinib targets include MET, AXL and VEGF-1, -2 and -3 receptors. In preclinical models, cabozantinib has been shown to inhibit the activity of these receptors, which are associated with tumor angiogenesis, invasiveness, metastasis and drug resistance.

On January 28, 2016, the European Medicines Agency (EMA) validated Exelixis’ Marketing Authorization Application (MAA) for cabozantinib as a treatment for patients with advanced renal cell carcinoma who have received one prior therapy. The MAA has been granted accelerated assessment, making it eligible for a 150-day review, versus the standard 210 days. On February 29, 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.

About the Cobimetinib and Vemurafenib Combination

Cobimetinib is a selective 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. In addition to the combination with vemurafenib in melanoma, cobimetinib is also being investigated in combination with several investigational medicines, including an immunotherapy, in several tumor types, including non-small cell lung cancer, colorectal cancer, triple-negative breast cancer and melanoma.

About Exelixis

Exelixis, Inc. is a biopharmaceutical company committed to developing small molecule therapies for the treatment of cancer. Exelixis is focusing its development and commercialization efforts primarily on cabozantinib, an internally discovered inhibitor of multiple receptor tyrosine kinases. Another Exelixis-discovered compound, COTELLIC™ (cobimetinib), a selective inhibitor of MEK, has been approved in Switzerland, the United States, the European Union, Canada and Australia, and is being evaluated by Roche and Genentech (a member of the Roche Group) in a broad development program under a collaboration with Exelixis. For more information, please visit the company’s website at www.exelixis.com.

Forward-Looking Statement Disclaimer

This press release contains forward-looking statements, including, without limitation, statements related to: the continued focus of Exelixis’ development efforts on the opportunities for cabozantinib in advanced RCC, advanced HCC, and other disease settings; Exelixis’ intent or understandings concerning the presentation of data at the upcoming 2016 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, June 3 – 7, 2016; and the continued progress on Exelixis’ mission to meaningfully improve the care and outcomes for people with cancer. Words such as “will,” “continue,” “focus,” “opportunities,” “potential,” “working,” or other similar expressions identify forward-looking statements, but the absence of these words does not necessarily mean that a statement is not forward-looking. In addition, any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements. These forward-looking statements are based upon Exelixis’ current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the clinical, therapeutic and commercial potential of cabozantinib and cobimetinib; Exelixis’ dependence on its relationship with Genentech/Roche with respect to cobimetinib and Exelixis’ ability to maintain its rights under the collaboration; the availability of data at the referenced times; risks and uncertainties related to regulatory review and approval processes and Exelixis’ compliance with applicable legal and regulatory requirements; Exelixis’ ability to conduct clinical trials of cabozantinib sufficient to achieve a positive completion; Exelixis’ reliance upon third-party vendors and clinical investigators; Exelixis’ ability to protect the company’s intellectual property rights; market competition; changes in economic and business conditions, and other factors discussed under the caption “Risk Factors” in Exelixis’ annual report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 29, 2016, and in Exelixis’ future filings with the SEC. The forward-looking statements made in this press release speak only as of the date of this press release. Exelixis expressly disclaims any duty, obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Exelixis’ expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based.

View source version on businesswire.com: http://www.businesswire.com/news/home/20160420006144/en/

Source: Exelixis, Inc.

Investors:
Exelixis, Inc.
Susan Hubbard, 650-837-8194
Investor Relations &
Corporate Communications
shubbard@exelixis.com
or
Media:
Exelixis, Inc.
Lindsay Treadway, 650-837-7522
Corporate Communications
ltreadway@exelixis.com