ALAMEDA, Calif.– Exelixis, Inc. (Nasdaq: EXEL) today announced detailed results from the expanded cohort 6 of the phase 1b COSMIC-021 trial of cabozantinib (CABOMETYX®) in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer (CRPC). Cohort 6 included patients with metastatic CRPC who had been previously treated with the novel hormone therapies (NHT) enzalutamide and/or abiraterone acetate used along with prednisone. The data are being presented during the Proffered Paper Session: GU Tumours, Prostate today at 1:30 p.m. CEST at the 2021 European Society of Medical Oncology (ESMO) Congress (LBA24).
Eligible patients in the trial had measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v 1.1) per investigator assessment, had progressed on prior NHT, and could have received prior docetaxel for metastatic hormone-sensitive disease. The analysis included 132 patients with metastatic CRPC, 101 of whom were high-risk, which was defined as having measurable visceral metastases and/or extrapelvic lymphadenopathy. The median follow-up for all patients was 15.2 months, and the primary endpoint was objective response rate (ORR) by investigator per RECIST 1.1.
As previously announced, in the high-risk patient population, investigator-assessed ORR was 27%, including 2% complete responses (CRs). The Blinded Independent Radiology Committee (BIRC)-assessed ORR was 18%, all partial responses (PRs). The disease control rate (CR + PR + stable disease) was 88% by investigator assessment and 84% by BIRC assessment.
New detailed results being presented at the 2021 ESMO Congress demonstrate that median progression-free survival per RECIST 1.1 for the high-risk population was 5.6 months (95% confidence interval [CI]: 5.4-8.2) as assessed by investigators and 6.8 months (95% CI: 5.5-9.7) as assessed by BIRC. The exploratory endpoint of overall survival for the high-risk patient population was 18.4 months (95% CI: 13.6-24.7). Tumor PD-L1 status, which was known for 75 patients, was not associated with response.
“These detailed results confirm previous findings from cohort 6 of COSMIC-021, further suggesting the promise cabozantinib in combination with atezolizumab may hold for patients with high-risk metastatic castration-resistant prostate cancer whose disease progressed following treatment with novel hormone therapy,” said Neeraj Agarwal, M.D., Professor of Medicine, Huntsman Cancer Institute, University of Utah and a trial investigator. “A significant number of these patients are looking for treatment options beyond chemotherapy, so these clinically meaningful response rates and progression-free survival results of cabozantinib in combination with atezolizumab are encouraging for this patient community and their physicians.”
The safety profile was consistent with that previously observed for each single agent. No new safety signals were observed. Discontinuation of both agents due to treatment-related adverse events (AEs) occurred in 10% of patients. Frequent treatment-related AEs were diarrhea (55%), fatigue (43%), nausea (42%) and decreased appetite (34%). Grade 3 or 4 treatment-related AEs occurred in 55% of patients (of which 3% experienced grade 4 AEs), and one grade 5 treatment-related AE was reported.
Following discussions with the U.S. Food and Drug Administration (FDA), Exelixis will not pursue a regulatory submission for the combination regimen based on cohort 6 of the COSMIC-021 trial. The CONTACT-02 study, a global phase 3 pivotal trial, initiated enrollment in June 2020 and is evaluating cabozantinib in combination with atezolizumab versus a second NHT in patients with metastatic CRPC who have been previously treated with one NHT. Pending results, CONTACT-02 may serve as a basis for future regulatory applications in this setting.
“We are pleased to provide a more detailed picture at ESMO of cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer who are in need of additional treatment options,” said Michael M. Morrissey, Ph.D., President and Chief Executive Officer, Exelixis. “The benefits of this combination regimen are encouraging, and we remain steadfast in our commitment to addressing unmet needs for patients with this form of prostate cancer. The CONTACT-02 continues to enroll patients, and we eagerly await a future readout from this global, phase 3 pivotal trial as we advance our goal of bringing treatments to patients with advanced, difficult-to-treat cancers.”
