Ipsen updates on CONTACT-02 Phase III trial in metastatic castration-resistant prostate cancer after final overall survival analysis

Ipsen recently shared the final results from the Phase III CONTACT-02 trial, which evaluated the combination of Cabometyx® (cabozantinib) and atezolizumab for the treatment of metastatic castration-resistant prostate cancer (mCRPC). The trial aimed to compare this new combination therapy against a second novel hormonal therapy (NHT) in men who had already been treated with one NHT and had measurable soft-tissue disease.

After a median follow-up of 24 months, the data revealed that the combination of Cabometyx and atezolizumab showed a numerical improvement in overall survival (OS) compared to a second NHT. However, this improvement was not statistically significant (hazard ratio: 0.89; 95% confidence interval: 0.72-1.10; P=0.296). Despite this, the trial did meet its other primary endpoint, which was progression-free survival (PFS), demonstrating a statistically significant benefit. The safety profile of the combination therapy was consistent with the known profiles of the individual drugs, with no new safety concerns identified.

Given the final OS analysis results and the anticipated regulatory challenges in countries where Ipsen holds commercialization rights (outside the US and Japan), Ipsen has decided not to pursue regulatory submissions for the combination therapy in mCRPC. Despite this, Ipsen remains confident in Cabometyx's efficacy as a monotherapy and in combination with immunotherapies for approved and potential future indications.

Cabometyx (cabozantinib) is a small molecule that targets multiple receptor tyrosine kinases, including VEGFRs, MET, RET, and the TAM family (TYRO3, MER, AXL). These kinases play roles in various cellular functions and pathological processes such as cancer development, metastasis, tumor angiogenesis, drug resistance, immune modulation, and the maintenance of the tumor microenvironment.

Exelixis has granted Ipsen exclusive rights to commercialize and further develop Cabometyx outside the US and Japan. In Japan, Takeda Pharmaceutical Company Limited holds the exclusive rights for commercialization and development. In the US, Exelixis retains these rights.

Cabometyx is currently approved in over 65 countries outside the US and Japan, including the European Union, for several indications: as a monotherapy for advanced renal cell carcinoma (aRCC) in adults with intermediate- or poor-risk disease, for those who have previously received VEGFR-targeted therapy, in combination with nivolumab for first-line treatment of aRCC in adults, as a monotherapy for locally advanced or metastatic differentiated thyroid carcinoma that is refractory to radioactive iodine and has progressed after prior systemic therapy, and as a monotherapy for hepatocellular carcinoma in adults previously treated with sorafenib.

Prostate cancer remains a major global health issue, being the second most common cancer in men and the fourth most common cancer overall. In 2020, there were over 1.4 million new cases and approximately 375,300 deaths worldwide. Prostate cancer is classified as mCRPC when it spreads beyond the prostate and does not respond to androgen-suppression therapies, which are standard treatments for prostate cancer. Prognosis for men with mCRPC is generally poor, with an estimated survival of 1-2 years.

The CONTACT-02 trial was a global, multicenter, randomized, Phase III, open-label study that included 575 patients. These patients were randomized into two groups: one received Cabometyx in combination with atezolizumab, and the other received a second NHT (either abiraterone and prednisone or enzalutamide). The primary endpoints were progression-free survival (PFS) and overall survival (OS), with the PFS analysis conducted in the first 400 randomized patients and the OS analysis conducted on the intent-to-treat (ITT) population of 507 patients. The secondary endpoint was objective response rate (ORR) assessed by a blinded independent radiology committee. The trial was sponsored by Exelixis and co-funded by Ipsen, Roche, and Takeda, with Takeda conducting the study in Japan.

Ipsen is a global biopharmaceutical company focused on Oncology, Rare Disease, and Neuroscience, with a pipeline supported by a century of development experience and global hubs in the US, France, and the UK. Ipsen’s reach extends to over 40 countries, bringing medicines to patients in more than 80 countries worldwide.