Exelixis and Ipsen Announce Detailed Results from Phase 3 COSMIC-311 Pivotal Trial of Cabozantinib in Patients with Previously Treated Radioactive Iodine-Refractory Differentiated Thyroid Cancer Presented at ASCO 2021

• New findings demonstrate the significant progression-free survival benefit seen in the intent-to-treat population was also consistent across subgroups
• Results from COSMIC-311 served as basis for Exelixis’ recent supplemental New Drug Application to U.S. Food and Drug Administration
• Data are in press to be published in The Lancet Oncology 

ALAMEDA, Calif. & PARIS – June 7, 2021 – Exelixis, Inc. (NASDAQ: EXEL) and Ipsen (Euronext:IPN; ADR:IPSEY) today announced detailed results from the phase 3 COSMIC-311 pivotal trial of cabozantinib (CABOMETYX®) in patients with previously treated radioactive iodine-refractory differentiated thyroid cancer (DTC). Results from the trial, which met the co-primary endpoint of significant improvement in progression-free survival (PFS) assessed by blinded independent radiology committee (BIRC), are in press to be published in The Lancet Oncology and have been submitted to the U.S. Food and Drug Administration (FDA). The data are being presented during the Oral Abstract Session: Head and Neck Cancer at 11:45 a.m. PT on Monday, June 7 at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting (abstract #6001).
“Following disease progression on anti-VEGFR therapy, patients with radioactive iodine-refractory differentiated thyroid cancer currently have no standard of care available to them, making the positive results of the COSMIC-311 trial an important clinical advance for this community in need of additional treatment options,” said Marcia S. Brose, M.D., Ph.D., Full Professor of Otorhinolaryngology: 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 COSMIC-311. “The significant improvement in progression-free survival and favorable trend for overall survival suggest cabozantinib could be an important new option for these patients.”
Results from COSMIC-311 served as the basis for the supplemental New Drug Application that Exelixis has submitted to the FDA, seeking an expanded indication for CABOMETYX for patients 12 and older with DTC that has progressed following prior therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).
As previously announced, at a planned interim analysis, cabozantinib demonstrated a significant reduction in the risk of disease progression or death of 78% versus placebo (hazard ratio [HR]: 0.22; 96% confidence interval [CI]: 0.13-0.36; P<0.0001) in the intent-to-treat (ITT) population. At a median follow-up of 6.2 months, median PFS was not reached (96% CI: 5.7 months – not estimable) in patients treated with cabozantinib and was 1.9 months (96% CI: 1.8-3.6 months) for placebo. The data presented at the 2021 ASCO Annual Meeting demonstrate that HRs for PFS consistently favored cabozantinib over placebo for prespecified subgroups, including age ≤65 vs. >65; prior treatment with lenvatinib (yes vs. no), and number of prior vascular endothelial growth factor receptor (VEGFR)-targeting therapies (1 vs. 2).
The results for the co-primary endpoint of objective response rate in the first 100 randomized patients after six months favored cabozantinib at 15% versus 0% for placebo, although this difference was not statistically significant (P=0.028). In the ITT population, a reduction in target lesion size was found in 76% of patients receiving cabozantinib versus 29% of patients receiving placebo; median overall survival was not reached in either treatment arm but favored cabozantinib (HR: 0.54; 95% CI: 0.27-1.11).
The safety profile was consistent with that previously observed for cabozantinib and adverse events (AEs) were managed with dose modifications. The discontinuation rate due to treatment-emergent AEs was 5% for cabozantinib versus 0% for placebo. The most common (≥5%) all-causality grade 3 or 4 AEs with cabozantinib were palmar-plantar erythrodysesthesia (10%), hypertension (9%), fatigue (8%), diarrhea (7%) and hypocalcemia (7%). There were no treatment-related deaths per investigator.
In February 2021, the U.S. FDA granted Breakthrough Therapy Designation to cabozantinib as a potential treatment for patients with DTC that has progressed following prior therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).
“We’re excited to offer a more detailed picture of results from the COSMIC-311 trial following the previous announcements that the trial met its co-primary endpoint of PFS, and that we received Breakthrough Therapy Designation for cabozantinib earlier this year,” said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. “The submission of our regulatory application for CABOMETYX to the FDA is an important step toward our goal of addressing an urgent treatment need for this patient community as soon as possible.”
“The results from the COSMIC-311 phase 3 trial have been highly anticipated, with the current survival time for people living with this uncommon form of differentiated thyroid cancer at just three to five years from the time metastatic lesions are detected,” said Howard Mayer, M.D., Executive Vice President and Head of Research and Development, Ipsen. “We’re delighted to share these data at ASCO together with Exelixis, highlighting our continued commitment to exploring the potential of cabozantinib across a range of hard-to-treat cancers. We look forward to working with regulatory authorities in our territories with the aim of bringing a meaningful new treatment option to a patient population in critical need.”

Attachment

• Ipsen-Exelixis-COSMIC-311-ASCO-7-June-2021