Exelixis initiates phase 3 trial with Cabometyx in radioiodine-refractory differentiated thyroid cancer (DTC) patients

Exelixis (EXEL) announced its initiation of a phase 3 pivotal trial (COSMIC-311) of Cabometyx (cabozantinib) in patients with radioiodine-refractory differentiated thyroid cancer (DTC) who have progressed after two prior vascular endothelial growth factor receptor (VEGFR)-targeted therapies.

The co-primary endpoints for the trial are progression-free (PFS) survival and objective response rate (ORR).

Why conducting trial on patients with radioiodine-refractory differentiated thyroid cancer.   

Differentiated thyroid tumors make up about 90 percent of all thyroid cancers. They are currently treated with surgery followed by ablation of the remaining thyroid with radioiodine. Around 5% – 15% of differentiated thyroid tumors resist the radioiodine treatment. The life expectancy for patients is only 3 – 6 years from the time metastatic lesions are detected.

Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis reminded that, Phase 1 and Phase 2 studies with cabozantinib have demonstrated encouraging clinical activity in patients with radioiodine-refractory differentiated thyroid cancer, suggesting it may be a promising treatment option for patients who have progressed after previous VEGFR-targeting therapy.

In general, thyroid cancer is diagnosed at a younger age than most other adult cancers. It is rapidly increasing in the U.S.. Approximately 54,000 new cases of thyroid cancer will be diagnosed in the U.S. in 2018 with three out of four cases to be diagnosed in women. Cancerous thyroid tumors include differentiated, medullary and anaplastic forms.

COSMIC-311 is a multicenter, randomized, double-blind, placebo-controlled phase 3 pivotal trial that aims to enroll approximately 300 patients at approximately 150 sites globally. Patients will be randomized in a 2:1 ratio to receive either cabozantinib 60 mg or placebo once daily.

Marcia Brose, M.D., Ph.D., Associate Professor of Otorhinolaryngology and head and neck Surgery and Director of the Center for Rare Cancers and Personalized Therapy at the Abramson Cancer Center of the University of Pennsylvania, and principal investigator of the trial explained, “There are limited options available to patients whose disease has progressed following anti-VEGFR therapy, there is an urgent need for new treatments.  Given the positive results from earlier stage trials, we are eager to learn more from this phase 3 study about Cabozantinib’s potential benefit in this patient population.”

More information about this trial is available at ClinicalTrials.gov.

Cabometyx (cabozantinib) is approved in the United States for advanced renal cell carcinoma (RCC). It is also approved in the European Union, Norway, Iceland, Australia, Switzerland and South Korea for advanced RCC in adults who have received prior VEGFR-targeted therapy, in the European Union for previously untreated intermediate or poor-risk advanced RCC and in Canada for adult patients with advanced RCC who have received prior VEGFR-targeted therapy.

In March 2017, the FDA granted orphan drug designation to cabozantinib for advanced hepatocellular carcinoma (HCC).

In May 2018, the FDA accepted Exelixis’ supplemental New Drug Application for Cabometyx for patients with previously treated HCC and assigned it a Prescription Drug User Fee Act action date of January 14, 2019.

On March 28, 2018Ipsen announced that the European Medicines Agency validated its application for a new indication for cabozantinib as a treatment for previously treated advanced HCC in the European Union.

On September 20, 2018, the CHMP provided a positive opinion for Cabometyx as a monotherapy for the treatment of HCC in adults who have been previously treated with sorafenib.

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.

CABOMETYX is currently not indicated for radioiodine-refractory DTC.

Please see Important Safety Information below and full U.S. prescribing information at https://cabometyx.com/downloads/CABOMETYXUSPI.pdf.

For important safety information read the company’s press release dated October 8, 2018.

* * * * * *

Exelixis has also announced that data from clinical trials of cabozantinib will be the subject of 13 presentations at the European Society for Medical Oncology (ESMO) 2018 Congress, which is being held October 19-23, 2018 in Munich, Germany.

Poster presentations will include results from:  

– The dose escalation stage of the phase 1b COSMIC-021 study of cabozantinib plus atezolizumab in previously untreated advanced RCC.

– A poster discussion session evaluating the effect of PD-L1 status on clinical outcomes with cabozantinib in advanced RCC in the CABOSUN and METEOR trials.

The data at ESMO displays the potential of cabozantinib across a range of difficult-to-treat cancers. Find the full schedule presentation details in the firm’s press release posted on October 8, 2018 at the Exelixis website.

Prohost Observations 

Exelixis has proven to have a solid science especially in oncology. Since the first approval of its drug cabozantinib, this firm worked hard on testing this drug on various cancers. Indeed, Exelixis is testing the drug as monotherapy and in combination with immunotherapy products.

In October 2017Exelixis announced that the independent data monitoring committee for the CELESTIAL study recommended stopping the trial for efficacy. Cabozantinib provided a statistically significant and clinically meaningful improvement in overall survival (OS) compared with placebo in patients with advanced HCC. In March 2017, the FDA granted orphan drug designation to cabozantinib for the treatment of advanced HCC.

Bottom line, we expect to hear soon about the approval of cabozantinib for liver cancer in Europe and in the United States.

Exelixis is one of the firms whose stocks we love accumulating following stock price declines caused by the market and investors circumstances or any reasons from among those that cause temporary decline in the stocks’ prices.

Leave a Reply