Cabozantinib plus atezolizumab improves progression-free survival in mCRPC

Treatment with cabozantinib (Cabometyx) in combination with atezolizumab (Tecentriq) significantly reduced the risk of disease progression or death compared with treatment with a second novel hormonal therapy (abiraterone [Zytiga] or enzalutamide [Xtandi]) in patients with metastatic castration-resistant prostate cancer (mCRPC) who had previously received treatment with a novel hormonal therapy, according to findings from the phase 3 CONTACT-02 trial (NCT04446117).¹

"Cabozantinib in combination with atezolizumab represents a potential new treatment modality for patients with metastatic castration-resistant prostate cancer," says Neeraj Agarwal, MD, FASCO.

Exelixis and Ipsen, the sponsor and co-funder of the CONTACT-02 trial, respectively, announced in a joint news release that the study met its co-primary end point of progression-free survival (PFS), as determined by a prespecified interim analysis of the data. The other primary end point of overall survival (OS) showed a trend toward improvement with the treatment combination, although the data have not yet met the threshold for significance. As planned, the trial will continue to the next analysis of OS.

The investigators expect results from the trial to be presented at an upcoming medical conference and shared with regulatory authorities.

“These positive findings from CONTACT-02 are highly encouraging given the need for additional, non-cytotoxic or non-chemotherapeutic treatment options for this patient population. Cabozantinib in combination with atezolizumab represents a potential new treatment modality for patients with metastatic castration-resistant prostate cancer, and we look forward to sharing the full data at a future medical meeting,” said lead investigator Neeraj Agarwal, MD, FASCO, in the news release.1 Agarwal is a professor and presidential endowed chair of cancer research at Huntsman Cancer Institute at the University of Utah in Salt Lake City, Utah.

In total, the global, multicenter, randomized CONTACT-02 trial² enrolled 575 patients with mCRPC and measurable visceral disease and/or extrapelvic adenopathy who were previously treated with 1 novel hormonal therapy. Patients were randomly assigned 1:1 to receive cabozantinib plus atezolizumab or a second novel hormonal therapy of either abiraterone and prednisone or enzalutamide. The co-primary end points of the study are PFS and OS. The study’s secondary end point is objective response rate.

In addition to efficacy data, the interim analysis showed that safety profiles of the experimental therapies were consistent with previously reported data.

Howard Mayer, MD, the executive vice president and head of research and development at Ipsen, concluded in the news release,¹ “These results represent the first positive phase 3 data of its kind for a tyrosine kinase inhibitor and immunotherapy combination in this indication. We will engage with regulatory authorities on these data and look forward to further exploring the potential treatment benefit for a patient population at such a challenging stage of disease.”

Reference

1. Exelixis and Ipsen announce positive results from phase 3 CONTACT—2 pivotal trial evaluating cabozantinib in combination with atezolizumab in metastatic castration-resistant prostate cancer. News release. Exelixis Inc and Ipsen. Published online and accessed August 21, 2023. https://www.businesswire.com/news/home/20230820936777/en/Exelixis-and-Ipsen-Announce-Positive-Results-from-Phase-3-CONTACT-02-Pivotal-Trial-Evaluating-Cabozantinib-in-Combination-with-Atezolizumab-in-Metastatic-Castration-Resistant-Prostate-Cancer

2. National Institutes of Health US National Library of Medicine ClinicalTrials.gov. Study of cabozantinib in combination with atezolizumab versus second NHT in subjects with mCRPC. Last updated July 17, 2023. Accessed August 21, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04446117