Cabozantinib Plus Atezolizumab Shows Promise in High-Risk Castration-Resistant Prostate Cancer

The combination of cabozantinib (Cabometyx) plus atezolizumab (Tecentriq) was found to elicit encouraging response rates, disease control, and acceptable safety in patients with metastatic castration-resistant prostate cancer (CRPC) who had previously received enzalutamide (Xtandi) and/or abiraterone acetate (Zytiga), according to data from cohort 6 of the phase 1b COSMIC-021 trial (NCT03170960).¹

Among 101 patients with high-risk disease, the investigator-assessed objective response rate (ORR) achieved with the combination was 27%; this comprised a complete response (CR) rate of 2% and a partial response (PR) rate of 25%.

The ORR per blinded independent radiology committee (BIRC) assessment was 18%, all of which were PRs. Additionally, the disease control rate (DCR) achieved with the doublet was 88% per investigator assessment, while it was 84% per BIRC assessment.

Progression-free survival and duration of response were found to be comparable between the investigator and BIRC assessments.

Detailed data from the trial will be shared at an upcoming medical conference in the second half of 2021, according to Exelixis Inc.

“These results from cohort 6 of COSMIC-021 suggest cabozantinib in combination with atezolizumab holds promise as a potential new treatment option in metastatic CRPC, a difficult-to-treat tumor type that typically has a poor prognosis,” Neeraj Agarwal, MD, professor of medicine at Huntsman Cancer Institute at the University of Utah and an investigator of the trial, stated 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 multicenter, open-label phase 1b trial is comprised of 2 parts: a dose-escalation phase and an expansion phase. The first phase enrolled patients with advanced renal cell carcinoma (RCC) with or without previous systemic therapy or with inoperable, locally advanced, metastatic or recurrent urothelial carcinoma following platinum-based treatment.

A total of 12 patients were enrolled to this portion of the trial and all had RCC. In this phase of the research, investigators identified 40 mg to be the optimal daily dose of cabozantinib plus 1200 mg of atezolizumab once every 3 weeks.

For the expansion portion of the trial, investigators are enrolling 24 cohorts spanning 12 cancer types: RCC, urothelial carcinoma, non–small cell lung cancer, CRPC, hepatocellular carcinoma, triple-negative breast cancer, epithelial ovarian cancer, endometrial cancer, gastric or gastroesophageal junction adenocarcinoma, colorectal adenocarcinoma, head and neck cancer, and differentiated thyroid cancer.

To be eligible for enrollment, patients needed to have measurable disease per RECIST v1.1 criteria and investigator assessment and had progressed on previous novel hormonal therapy. Notably, patients were allowed to have received previous docetaxel for hormone-sensitive disease.

A total of 132 patients were included in the analysis and 101 had high-risk disease, which was determined to be those with measurable visceral and/or extrapelvic lymph node metastases. The primary end point of the trial was investigator-assessed ORR per RECIST v1.1 criteria. The median follow-up of this patient subset was 15.8 months.

Prior data from an interim analysis of cohort 6 presented at the 2020 ASCO Virtual Scientific Program showed that the doublet resulted in a 32% ORR per RECIST v1.1 criteria in 44 patients who had previously received enzalutamide and/or abiraterone, with a DCR of 80%.² Preliminary findings from the trial did not suggest a link between PD-L1 expression and antitumor activity, which may indicate that patients with or without PD-L1 expression may be responsive to treatment with the combination.

Regarding safety, the toxicity profile of the combination was determined to be reflective of what has been previously reported with both agents as monotherapies, with no new signals observed. Twelve percent of patients discontinued treatment with the regimen due to toxicities that were determined to be unrelated to progressive disease.

“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, Product Development and Medical Affairs and chief medical officer, Exelixis, added in the 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.”

Exelixis announced their plan to share the results with the FDA to identify the next step toward a regulatory submission for the doublet as a treatment option for patients with high-risk metastatic CRPC.

The phase 3 CONTACT-02 trial (NCT04446117) is currently examining cabozantinib plus atezolizumab vs a second hormonal therapy in patients with metastatic CRPC who had received prior treatment with 1 novel hormonal therapy.

References

1. Exelixis announces phase 1b results from cohort 6 of COSMIC-021 trial in patients with metastatic castration-resistant prostate cancer. News release. Exelixis, Inc. May 24, 2021. Accessed May 28, 2021. https://bwnews.pr/2TqmmAc
2. Exelixis announces results from COSMIC-021 trial of cabozantinib in combination with atezolizumab in multiple advanced solid tumor types. News release. Exelixis, Inc. May 13, 2020. Accessed May 28, 2021. https://bit.ly/3wBUOpO