Cabozantinib/Atezolizumab Fails to Meet OS Endpoint in mCRPC, Regulatory Submissions Limited
核心洞察
The Phase III CONTACT-02 trial evaluated cabozantinib plus atezolizumab versus a second novel hormonal therapy in metastatic castration-resistant prostate cancer (搜索) (mCRPC (搜索)).
While the combination showed a positive trend in overall survival (OS), it did not reach statistical significance (HR: 0.89; 95% CI: 0.72-1.10; P=0.296).
Ipsen will not pursue regulatory submissions for the cabozantinib/atezolizumab combination in mCRPC (搜索) in countries outside the US and Japan, despite a statistically significant PFS benefit.
Ipsen's Phase III CONTACT-02 trial, investigating Cabometyx® (cabozantinib) in combination with atezolizumab for metastatic castration-resistant prostate cancer (搜索) (mCRPC (搜索)), demonstrated a positive trend towards improved overall survival (OS) but failed to reach statistical significance. The trial compared the combination regimen to a second novel hormonal therapy (NHT) in men previously treated with one NHT and measurable soft-tissue disease. While the trial met its other primary endpoint of progression-free survival (PFS), Ipsen will not pursue regulatory submissions for the combination in countries where it holds commercialization rights (outside the US and Japan).
CONTACT-02 Trial Results
At a median follow-up of 24.0 months, the final OS data showed a numerical but not statistically significant improvement in OS for the cabozantinib/atezolizumab combination versus a second NHT (hazard ratio: 0.89; 95% confidence interval: 0.72-1.10; P=0.296). The trial had previously demonstrated a statistically significant benefit in PFS. Safety for the combination was consistent with the known safety profiles of the individual medicines, with no new safety signals identified.
The progression-free survival (PFS) analysis showed that in the intent-to-treat (ITT) population, the median PFS was 6.3 months (95% CI, 6.2-8.8) in the cabozantinib/atezolizumab arm vs 4.2 months (95% CI, 3.7-5.7) in the second NHT arm (HR, 0.65; 95% CI, 0.50-0.84; P = .0007).
Subgroup Analysis
Subgroup analyses revealed potential benefits in specific patient populations. In patients with liver metastasis, the combination of cabozantinib and atezolizumab was associated with a 32% reduction in the risk of death vs a second NHT (HR, 0.68; 95% CI, 0.47-1.00; P = .051). In this subgroup, the median OS was 12.2 months (95% CI, 8.8-13.8) with cabozantinib/atezolizumab vs 7.1 months (95% CI, 5.3-10.4) with a second NHT.
In patients with bone metastasis, the median OS was 13.8 months (95% CI, 11.9-16.3) in the cabozantinib/atezolizumab cohort vs 11.6 months (95% CI, 10.5-14.1) in the second NHT cohort, translating to a 21% reduction in the risk of death in the treatment arm (HR, 0.79; 95% CI, 0.63-1.00; P = .046).
Implications and Future Directions
Despite the lack of statistical significance in overall survival for the entire study population, Exelixis plans to submit a new drug application to the FDA for the combination of cabozantinib plus atezolizumab in mCRPC (搜索). Ipsen, however, will not pursue regulatory submissions for this combination regimen in mCRPC in countries where Ipsen has commercialization rights (outside of the US and Japan).
The CONTACT-02 trial enrolled 575 patients with mCRPC (搜索) who had measurable extra-pelvic soft tissue metastasis and had progressed on one prior NHT. Patients were randomized 1:1 to receive cabozantinib (40 mg PO QD) plus atezolizumab (1200 mg IV Q3W) or a second NHT (abiraterone [1000 mg PO QD plus prednisone 5 mg PO BID] or enzalutamide [160 mg PO QD]).