Exelixis Announces Phase 1b Results from Cohort 6 of COSMIC-021 Trial in Patients with Metastatic Castration-Resistant Prostate Cancer

Exelixis, Inc. (NASDAQ: EXEL) today announced results from the metastatic castration-resistant prostate cancer (CRPC) cohort 6 of COSMIC-021, the phase 1b trial of cabozantinib (CABOMETYX®) in combination with atezolizumab in patients with locally advanced or metastatic solid tumors. Cohort 6 included patients with metastatic CRPC who had been previously treated with enzalutamide and/or abiraterone acetate.

Upon enrollment, patients had to have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1) per investigator assessment, had progressed on prior novel hormonal therapy, and could have received prior docetaxel for hormone-sensitive disease. The analysis included 132 patients, 101 of whom had high-risk disease, defined as measurable visceral and/or extra-pelvic lymph node metastases. The group with high-risk disease is the patient population for which Exelixis would pursue a U.S. regulatory filing. The median follow-up for the high-risk patients was 15.8 months. The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v. 1.1.

In the high-risk population, the investigator-assessed ORR was 27%, including 2% complete responses (CR) and 25% partial responses (PR). The Blinded Independent Radiology Committee (BIRC)-assessed ORR was 18%, all of which were partial responses. The disease control rate (CR + PR + stable disease) was 88% and 84% per investigator and BIRC assessment, respectively. Other radiographic endpoints, namely progression-free survival and duration of response, were similar between the investigator and BIRC assessment. Detailed results of the trial will be presented at a medical meeting in the second half of 2021.

An interim analysis of the initial 44 patients enrolled in the cohort was previously presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program.

“These results from cohort 6 of COSMIC-021 suggest cabozantinib in combination with atezolizumab holds promise as a potential new treatment option in metastatic castration-resistant prostate cancer, a difficult-to-treat tumor type that typically has a poor prognosis,” said Neeraj Agarwal, M.D., Professor of Medicine, Huntsman Cancer Institute, University of Utah and an investigator of the trial. “There is a significant need for more options beyond chemotherapy once patients progress on androgen-deprivation therapy, so it is encouraging to see the response rates, disease control and tolerable safety profile associated with cabozantinib in combination with atezolizumab in this trial.”

The adverse event profile observed in the study was reflective of the known safety profile for each single agent. No new safety signals were identified in this expanded combination cohort. Discontinuation of treatment due to adverse events unrelated to disease progression was 12%.

In continuation of prior regulatory interaction and feedback from the U.S. Food & Drug Administration (FDA), Exelixis intends to discuss the results with the FDA to determine next steps toward a regulatory submission for the combination regimen for patients with high-risk metastatic CRPC. The global phase 3 trial, CONTACT-02, initiated enrollment in June 2020 and is evaluating cabozantinib in combination with atezolizumab versus a second novel hormonal therapy in patients with metastatic CRPC who have been previously treated with one novel hormonal therapy.

“Many patients with metastatic castration-resistant prostate cancer who have progressed on a novel hormonal therapy wish to avoid or delay chemotherapy. These results of the COSMIC-021 cohort 6 suggest the combination of cabozantinib and atezolizumab may offer this patient population a new treatment option,” said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. “We look forward to building on these results with the phase 3 CONTACT-02 trial in our continued effort to bring cabozantinib to many more patients in need.”

More information about this trial (NCT03170960) is available at ClinicalTrials.gov.

About the COSMIC-021 Study

COSMIC-021 is a multicenter, phase 1b, open-label study that is divided into two parts: a dose-escalation phase and an expansion cohort phase. The dose-escalation phase was designed to enroll patients either with advanced renal cell carcinoma (RCC) with or without prior systemic therapy or with inoperable, locally advanced, metastatic or recurrent urothelial carcinoma (UC), (including renal, pelvis, ureter, urinary bladder an