Ipsen Halts Cabometyx Prostate Cancer Combo After Phase III Failure

Prostate cancer remains the second most prevalent cancer among men and is the fourth most common cancer worldwide. Prostate cancer is deemed metastatic castration-resistant prostate cancer (mCRPC) when it spreads beyond the prostate gland and does not respond to androgen-suppression therapy, a standard treatment.

Ipsen, a French biopharmaceutical company, reported that its Phase III CONTACT-02 trial aimed at evaluating the effectiveness of Cabometyx (cabozantinib) in combination with Roche’s Tecentriq (atezolizumab) for treating mCRPC, did not achieve one of its primary goals. The trial, which included 575 participants, failed to demonstrate a statistically significant improvement in overall survival (OS) at the 24-month mark.

The CONTACT-02 trial was initiated to see if combining Cabometyx with Tecentriq could offer an additional treatment option for prostate cancer. The trial focused on men who had previously been treated with one novel hormonal therapy (NHT) and had measurable soft-tissue disease. While the trial did show promise by meeting its other primary endpoint of progression-free survival (PFS) last year—patients receiving the combo therapy experienced 6.3 months without disease progression compared to 4.2 months in the control group—it did not meet the crucial OS endpoint.

Despite the setback, Ipsen noted that the safety profile for the combination therapy remained consistent with the known profiles of the individual drugs. There were no new safety concerns observed from the study data. However, due to the unmet OS endpoint and the challenging regulatory environment, Ipsen has decided not to pursue regulatory submissions for this combination therapy in mCRPC outside the US and Japan.

The rights to commercialize and develop Cabometyx have been divided among several companies: Ipsen handles territories outside the US and Japan, Exelixis retains the US rights, and Takeda is responsible for Japan following deals struck in 2016 and 2017. Ipsen has already secured approvals for Cabometyx in renal cell carcinoma, thyroid carcinoma, and hepatocellular carcinoma across more than 60 countries, including the EU. The drug generated $579 million in revenue for Ipsen last year, with projected peak sales estimated to reach $826 million by 2028, according to GlobalData.

Exelixis, despite the trial’s failure to meet the OS endpoint, remains optimistic. The company pointed out that there was still an improvement in OS observed in various clinical subgroups. Exelixis plans to move forward with submitting a supplemental new drug application to the US Food and Drug Administration (FDA) for the combination therapy in mCRPC later this year.

Amy Peterson, Exelixis’s chief medical officer, expressed that the CONTACT-02 trial results indicate potential benefits for certain patient groups from the Cabometyx and Tecentriq combination. She suggested that this regimen could serve as a valuable addition to the treatment landscape for advanced prostate cancer.

Ipsen continues to have faith in Cabometyx, especially as a monotherapy and in combination with immunotherapy for already approved indications. The company is optimistic about the drug’s future potential despite the recent trial’s missed endpoint.