Ipsen Discontinues Cabometyx Combination for Prostate Cancer After Phase III Failure
核心洞察
Ipsen will not pursue regulatory submissions for Cabometyx (cabozantinib) combined with Tecentriq (atezolizumab) in metastatic castration-resistant prostate cancer (搜索) (mCRPC (搜索)) outside the US and Japan.
The decision follows the CONTACT-02 Phase III trial, which failed to achieve statistical significance in overall survival (OS) improvement at 24 months.
Despite the setback, Exelixis plans to proceed with a supplemental new drug application to the FDA for the combination therapy in mCRPC (搜索) in the US.
Ipsen has decided to discontinue pursuing regulatory submissions for its oncology asset, Cabometyx (cabozantinib), in combination with Roche's Tecentriq (atezolizumab), for prostate cancer (搜索) outside the US and Japan. This decision follows the Phase III CONTACT-02 trial, which did not meet its primary endpoint of overall survival (OS) improvement at 24 months.
The CONTACT-02 trial (NCT04446117) investigated the Cabometyx and Tecentriq combination in patients with metastatic castration-resistant prostate cancer (搜索) (mCRPC (搜索)). According to a press release on September 15, the trial failed to demonstrate a statistically significant improvement in OS at the 24-month mark.
Strategic Shift
Based on these results and the “challenging regulatory environment,” the French biopharma company has opted not to pursue regulatory submissions for the combination therapy in mCRPC (搜索). Ipsen retains commercialization and development rights for Cabometyx in territories outside the US and Japan, stemming from a 2016 agreement with Exelixis, the drug's original developer. Exelixis maintained US rights, while Takeda (搜索) secured Japanese rights in 2017.
Cabometyx has been approved for renal cell carcinoma (搜索), thyroid carcinoma (搜索), and hepatocellular carcinoma (搜索) in over 60 countries, including those within the EU, under Ipsen's oversight. The tyrosine kinase inhibitor (TKI) generated $579 million for Ipsen last year, with projected peak sales of $826 million in 2028, according to GlobalData’s Pharma Intelligence Center.
Trial Details and Results
The CONTACT-02 trial aimed to expand Cabometyx’s application in oncology by comparing the combination therapy to a second novel hormonal therapy (NHT) in men previously treated with one NHT and who had measurable soft-tissue disease. Prostate cancer (搜索) is the second most common cancer in men and the fourth most common cancer overall globally. mCRPC (搜索) is defined as prostate cancer that has spread beyond the prostate and no longer responds to androgen-suppression therapies.
The global study, which enrolled 575 patients, initially showed promise by meeting its other primary endpoint of progression-free survival last year. Patients receiving the combination therapy experienced a median progression-free survival of 6.3 months, compared to 4.2 months in the control group.
The safety profile of the combination was consistent with the known profiles of the individual medicines, with no new safety signals identified. However, the failure to meet the OS endpoint has effectively ended Ipsen’s pursuit of Cabometyx for prostate cancer (搜索).
Future Plans for Cabometyx
Ipsen remains confident in Cabometyx’s use as a monotherapy and in combination with immunotherapy across approved indications, as well as its ongoing future potential. Despite the missed endpoint, Exelixis indicated in its press release that improvements in OS were observed in multiple clinical subgroups. The company plans to proceed with a supplemental new drug application to the US Food and Drug Administration (FDA) for the combination therapy in mCRPC (搜索) later this year.
Exelixis’s chief medical officer, Amy Peterson, stated, “The results from the CONTACT-02 trial suggest that there are patients who could benefit from Cabometyx in combination with Tecentriq and that this regimen could be a valuable addition to the treatment landscape for patients with advanced prostate cancer (搜索).”