Cabozantinib Plus Atezolizumab Moves Toward Regulatory Filing in High-Risk mCRPC


Promising results from a phase 1b trial of cabozantinib in combination with atezolizumab for patients with high-risk, locally advanced or metastatic castration-resistant prostate cancer are expected to lead to regulatory submission.

Results from cohort 6 of the phase 1b COSMIC-021 trial (NCT03170960) have demonstrated feasibility of cabozantinib (Cabometyx) in combination with atezolizumab (Tecentriq) in patients with high-risk, locally advanced or metastatic castration-resistant prostate cancer (CRPC), according to the company responsible for the tyrosine kinase inhibitor, Exelixis Inc.1

The objective response rate (ORR) by investigator assessment in this patient population was 27%, including 2% with complete responses. By blinded independent radiology review (BICR), the ORR was 18% comprised of all partial responses. The rates of disease control were 88% and 84%, respectively.

“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,” trial investigator Neeraj Agarwal, MD, professor of medicine at Huntsman Cancer Institute of the University of Utah, said in a press release. “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 analysis that included 132 patients enrolled a high proportion of patients with high-risk disease (n = 101), which was defined by the presence of measurable visceral and/or extra-pelvic lymph node metastases. The cohort included patients who were previously treated with enzalutamide (Xtandi) and abiraterone acetate (Zytiga).

Median follow-up was 15.8 months, with progression-free survival and duration of response results similar between the BICR and investigator assessment.

The adverse effects profile for the combination was in line with the known safety profiles of each agent. No new safety signals were identified and discontinuation of treatment unrelated to disease progression occurred in 12% of patients.

Interim analysis for this cohort was previously presented at the American Society of Clinical Oncology (ASCO) 2020Virtual Scientific Program. In 44 enrolled patients, the ORR was 32% and the disease control rate was 80%. Data at the time did not suggest an association between PD-L1 expression and activity of the regimen.2

Based on these results, Exelixis has plans to pursue regulatory filing with the FDA for use of the combination in the high-risk subgroup of patients with metastatic CRPC. The global phase 3 CONTACT-02 trial (NCT04446117) started enrolling patients in June 2020 and is examining the TKI/PD-L1 inhibitor combination versus a second novel hormonal therapy in patients with CRPC who have previously received 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,” Gisela Schwab, MD, president of Product Development and Medical Affairs, and Chief Medical Officer at Exelixis, said in a press release. “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.”

The company has plans to present the findings from cohort 6 of COSMIS-021 at an upcoming medical meeting in the second half of 2021. The trial has 24 cohorts examining the combination across different tumor types, including urothelial carcinoma, non–small cell lung cancer, differentiated thyroid cancer, head and neck cancer, and colorectal cancer, among others.


1. Exelixis Announces Phase 1b Results from Cohort 6 of COSMIC-021 Trial in Patients with Metastatic Castration-Resistant Prostate Cancer. News release. Exelixis. May 24, 2021. Accessed May 25, 2021.

2. Exelixis Announces Results From COSMIC-021 Trial of Cabozantinib in Combination With Atezolizumab in Multiple Advanced Solid Tumor Types. News release. Exelixis. May 13, 2020. Accessed May 25, 2021.

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