Exelixis Reveals Final Survival Data from Phase 3 Study on Cabozantinib Combination in Metastatic Prostate Cancer at ESMO 2024

Exelixis, Inc. recently shared detailed findings from the CONTACT-02 phase 3 study evaluating cabozantinib (marketed as CABOMETYX) in combination with atezolizumab (Tecentriq) in patients with metastatic castration-resistant prostate cancer (mCRPC). This study specifically targeted patients with measurable extra-pelvic soft tissue disease who had already undergone one novel hormonal therapy (NHT). The results were presented at the 2024 European Society for Medical Oncology Congress (ESMO 2024).

Dr. Neeraj Agarwal, a senior director at Huntsman Cancer Institute and the global lead investigator, emphasized the critical need for innovative treatments in patients whose mCRPC has progressed despite prior therapies. He highlighted the particularly poor outcomes for those with liver metastases. The data from CONTACT-02 suggest that the combination of cabozantinib and atezolizumab could be beneficial, especially for these high-risk patients.

The CONTACT-02 study aimed to assess both progression-free survival (PFS) and overall survival (OS) as its primary endpoints. After a median follow-up of 24 months, the final OS analysis indicated a numerical improvement favoring the combination therapy (hazard ratio: 0.89; 95% confidence interval: 0.72-1.10; P=0.296), though it was not statistically significant. Importantly, the combination therapy demonstrated a pronounced benefit in patients with bone or liver metastases, with a hazard ratio of 0.68 (95% CI: 0.47-1.00; P=0.051) for liver metastases.

Amy Peterson, M.D., Executive Vice President at Exelixis, noted the increasing prevalence of patients with mCRPC and extra-pelvic soft tissue metastases who do not respond to NHTs, underscoring the demand for effective treatments. The positive outcomes from CONTACT-02 support the potential role of cabozantinib combined with atezolizumab in enhancing the treatment landscape for advanced prostate cancer.

Safety profiles were comparable between the treatment groups, with treatment-related grade 3-4 adverse events observed in 40% of patients receiving the combination therapy, compared to 8% in the NHT group. The incidence of treatment discontinuation due to adverse events was similar between the two groups. Additionally, the combination therapy did not negatively impact the patients' quality of life.

Previously, CONTACT-02 had met its primary endpoint for PFS, demonstrating a significant benefit in the predefined PFS intent-to-treat (ITT) population. These results were initially shared at the American Society of Clinical Oncology 2024 Genitourinary Cancers Symposium. Exelixis plans to submit a supplemental New Drug Application to the U.S. FDA for cabozantinib in combination with atezolizumab for mCRPC later this year.

The CONTACT-02 trial was a global, multicenter, open-label study involving 575 patients who were randomized to receive either the experimental combination of cabozantinib and atezolizumab or a second NHT (abiraterone with prednisone or enzalutamide). The primary endpoints of the trial were PFS and OS, and the secondary endpoint was the objective response rate per a blinded independent radiology committee. The trial was sponsored by Exelixis and co-funded by Ipsen, Roche, and Takeda Pharmaceutical Company Limited, with Takeda handling the trial in Japan.

Prostate cancer remains a significant health challenge, with the American Cancer Society estimating approximately 299,000 new cases and over 35,000 deaths in the U.S. in 2024. Advanced prostate cancer that does not respond to androgen-suppression therapies is classified as mCRPC, a condition that typically has a poor prognosis with a survival rate of 1-2 years.

CABOMETYX (cabozantinib) is an approved therapy in the U.S. for various cancers, including renal cell carcinoma and hepatocellular carcinoma, among others. It has regulatory approval in over 65 countries outside the U.S. and Japan. However, it is not currently indicated for the treatment of CRPC.