Exelixis Announces Clinical Trial Collaboration with Roche to Evaluate Cabozantinib and Atezolizumab in Locally Advanced or Metastatic Solid Tumors

SOUTH SAN FRANCISCO, CA, USA I February 27, 2017 I Exelixis, Inc. (EXEL) today announced a new collaboration with Roche on a phase 1b dose escalation study that will evaluate the safety and tolerability of cabozantinib, Exelixis’ tyrosine kinase inhibitor (TKI), in combination with atezolizumab, Roche’s anti-PD-L1 immunotherapy, in patients with locally advanced or metastatic solid tumors. Enrollment is scheduled to begin mid-year 2017; Exelixis will be the sponsor of the trial, and Roche will provide atezolizumab.

Based on the dose-escalation results, the trial has the potential to enroll up to four expansion cohorts, including a cohort of patients with previously untreated advanced clear cell renal cell carcinoma (RCC) and three cohorts of urothelial carcinoma (UC), namely platinum eligible first-line patients, first- or second-line platinum ineligible patients, and patients previously treated with platinum-containing chemotherapy. Ipsen, Exelixis’ global partner for cabozantinib, except in the United States and Japan, will participate in this study and have access to the results for potential future development in its territories. Takeda may also participate in these and future studies and have access to the results to support potential future regulatory submissions in their territories, if they opt into their funding obligations under the respective collaboration agreement.

“People with advanced genitorurinary malignancies are in need of additional treatment options that can improve clinical outcomes,” said Sumanta Kumar Pal, M.D., co-director, Kidney Cancer Program at City of Hope, and principal investigator in the study. “The combined approach of tyrosine kinase inhibition with cabozantinib alongside immune-checkpoint inhibition has already shown promise in an early phase 1 clinical trial. We look forward to further examining this potential with cabozantinib plus atezolizumab to treat a range of genitourinary and other tumors.”

“We are pleased to collaborate with Roche to study the potential of atezolizumab in combination with cabozantinib, our lead medicine that is the subject of a broad development program across a variety of cancers,” said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. “Although several therapies have recently received regulatory approval to treat advanced kidney and bladder cancers, survival continues largely to be measured in months, not years. Evaluating how cabozantinib may positively impact treatment when paired with immunotherapy is central to our goal of improving therapeutic outcomes for patients with these and other cancers.”

The rationale for the collaboration is based on clinical and preclinical observations consistent with the ability of cabozantinib to promote an immunopermissive environment, which might present an opportunity for synergistic effects from combination treatment with immune checkpoint inhibitors and other immunotherapies.1,2 In an ongoing phase 1 clinical trial in subjects with refractory metastatic UC and other genitourinary tumors, cabozantinib has been evaluated in combination with nivolumab, a monoclonal antibody to PD-1. The combination was well-tolerated among all enrolled subjects, no dose-limiting toxicities were reported, and the recommended phase 2 dose was determined to be 40 mg qd for cabozantinib with 3 mg/kg of nivolumab (intravenous [IV], once every two weeks).3 Updated results from this part of the study as well as results from a second part evaluating the combination of cabozantinib, nivolumab and ipilimumab were presented during the poster session (Abstract #293) on February 17 at the American Society of Clinical Oncology 2017 Genitourinary Cancers Symposium, which was held in Orlando, Florida, February 16 – 18, 2017.

Exelixis’ cabozantinib is a potent inhibitor of multiple receptor tyrosine kinases known to play important roles in tumor cell proliferation and/or tumor neovascularization including MET, VEGFR, AXL and RET. Some of these receptors have also been implicated in promoting an immunosuppressive tumor microenvironment. Cabozantinib has demonstrated broad preclinical and clinical activity across several tumor types. Cabozantinib tablets (60 mg) are approved as CABOMETYX™ in the United States and Europe for patients with advanced RCC who have received prior anti-angiogenic/VEGF-targeted therapy, and cabozantinib capsules (140 mg) are approved as COMETRIQ® for the treatment of progressive, metastatic medullary thyroid cancer (MTC) in the United States and Europe.

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 and urothelial carcinoma.4

Kidney cancer is among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S., according to the American Cancer Society’s 2016 statistics.5 Clear cell RCC is the most common type of kidney cancer in adults.6 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.5 Approximately 30,000 patients in the U.S. and 68,000 globally require treatment.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 renal cell carcinoma who have received prior anti-angiogenic therapy. On September 9, 2016, the European Commission approved CABOMETYX tablets for the treatment of advanced renal cell carcinoma in adults who have received prior vascular endothelial growth factor (VEGF)-targeted therapy in the European Union, Norway and Iceland. 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. On December 21, 2016, this agreement was amended to include commercialization rights for Ipsen in Canada. On January 30, 2017, Exelixis and Takeda jointly announced an exclusive licensing agreement for the commercialization and further development of cabozantinib indications in Japan.

About Exelixis

Exelixis, Inc. (EXEL) is a biopharmaceutical company committed to the discovery, development and commercialization of new medicines to improve care and outcomes for people with cancer. Since its founding in 1994, three products discovered at Exelixis have progressed through clinical development, received regulatory approval, and entered the marketplace. Two are derived from cabozantinib, an inhibitor of multiple tyrosine kinases including MET, AXL and VEGF receptors: CABOMETYX™ tablets approved for previously treated advanced kidney cancer and COMETRIQ® capsules approved for progressive, metastatic medullary thyroid cancer. The third product, Cotellic®, is a formulation of cobimetinib, a selective inhibitor of MEK, is marketed under a collaboration with Genentech (a member of the Roche Group), and is approved as part of a combination regimen to treat advanced melanoma. Both cabozantinib and cobimetinib have shown potential in a variety of forms of cancer and are the subjects of broad clinical development programs. For more information on Exelixis, please visit www.exelixis.com or follow @ExelixisInc on Twitter.

SOURCE: Exelixis

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