Trial results for the combination of atezolizumab and cabozantinib in men with metastatic castration-resistant prostate cancer (mCRPC) were posted on ClinicalTrials.gov on 2025-12-18. The study demonstrated that the combination therapy significantly improved median progression-free survival (PFS) to 6.34 months compared to 4.17 months for a second novel hormonal therapy (NHT) control arm, with a Cox Proportional Hazard ratio of 0.65 (95% CI: 0.5 to 0.84) and a p-value of 0.0007.
Background
Atezolizumab is an immunotherapy, and cabozantinib is a small molecule kinase inhibitor. This study investigated their combination in patients with metastatic castration-resistant prostate cancer (mCRPC), a form of prostate cancer that has spread to other parts of the body and no longer responds to treatments that lower testosterone levels.
Trial design
The study (NCT04446117) was a Phase 3, multi-center, randomized, open-label, controlled study that enrolled 575 subjects. It investigated the combination of cabozantinib and atezolizumab versus a second novel hormonal therapy (NHT) in men with metastatic castration-resistant prostate cancer (mCRPC) who had previously received one NHT. The control arm included therapies such as abiraterone acetate, enzalutamide, and prednisone.
Key results
The trial evaluated the duration of progression-free survival (PFS) and overall survival (OS).
For the outcome of "Duration of Progression Free Survival (PFS) Per Response Evaluable Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Radiology Committee (BIRC)":
- The Experimental Arm (Cabozantinib and Atezolizumab) had a median PFS of 6.34 months.
- The Control Arm (Second NHT) had a median PFS of 4.17 months.
A Log Rank analysis yielded a Cox Proportional Hazard ratio of 0.65 (95% Confidence Interval: 0.5 to 0.84) with a p-value of 0.0007.
For the outcome of "Duration of Overall Survival (OS)":
- The Experimental Arm (Cabozantinib and Atezolizumab) had a median OS of 14.78 months.
- The Control Arm (Second NHT) had a median OS of 14.98 months.
A Log Rank analysis yielded a Cox Proportional Hazard ratio of 0.89 (95% Confidence Interval: 0.72 to 1.1) with a p-value of 0.2956.
What this means
The results indicate that the combination of cabozantinib and atezolizumab significantly extended progression-free survival in men with mCRPC who had previously received one novel hormonal therapy. The median PFS was notably longer in the experimental arm compared to the control arm, supported by a statistically significant p-value and hazard ratio. While an improvement in overall survival was not statistically significant in this analysis, the PFS benefit suggests a potential clinical advantage for this combination in managing disease progression in this patient population.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04446117, titled "Study of Cabozantinib in Combination With Atezolizumab Versus Second NHT in Subjects With mCRPC," were posted on 2025-12-18 on clinicaltrials.gov.