Atezolizumab Plus Cabozantinib Meets PFS End Point in Phase 3 CONTACT-02 Trial in Hormone Therapy–Pretreated mCRPC

Atezolizumab Plus Cabozantinib Meets PFS End Point in Phase 3 CONTACT-02 Trial in Hormone Therapy–Pretreated mCRPC

Patients with metastatic castration-resistant prostate cancer (mCRPC) and measurable soft tissue disease following 1 prior novel hormonal therapy achieved statistically significant progression-free survival (PFS) following combined treatment with cabozantinib (Cabometyx) and atezolizumab (Tecentriq) compared with a second novel hormonal therapy. The dual regimen therefore met one of the primary end points in the primary analysis of the phase 3 CONTACT-02 trial (NCT04446117).¹

In addition, a prespecified interim analysis was conducted for overall survival (OS), the other primary end point of the trial. Despite a trend in favor of the combination, the data were immature and did not reach the threshold for statistical significance. As such, the trial will continue to its next OS analysis as planned.

Regarding the safety profile of the combination, no new signals were identified, and the adverse effects (AEs) were in line with the established safety profiles of cabozantinib and atezolizumab alone.

“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,” Neeraj Agarwal, MD, FASCO, professor and Presidential Endowed Chair of Cancer Research at Huntsman Cancer Institute, University of Utah, and the global lead investigator of the trial, said in a news release. “Cabozantinib in combination with atezolizumab represents a potential new treatment modality for patients with mCRPC, and we look forward to sharing the full data at a future medical meeting.”

CONTACT-02 is a global, multicenter, randomized, phase 3, open-label study, in which 575 patients were randomly assigned 1:1 to cabozantinib plus atezolizumab or a second novel hormonal therapy of either abiraterone acetate (Zytiga) and prednisone or enzalutamide (Xtandi).

To be eligible for enrollment, patients at least 18 years of age must have received a diagnosis of mCRPC with measurable visceral disease or measurable extrapelvic adenopathy following treatment with one novel hormonal therapy, including abiraterone acetate, apalutamide (Erleada), darolutamide (Nubeqa), or enzalutamide, with progressive disease defined by parameters for prostate-specific antigen progression or soft tissue disease progression. Additionally, serum testosterone must have been 50 ng/dL or lower at screening. An ECOG performance status of 0 or 1, recovery to baseline or grade 1 or lower AEs from prior therapy, and adequate organ and marrow function were also required.

The two primary end points of the trial are PFS and OS. Objective response rate (ORR) will be measured as a secondary end point. Both PFS and ORR will be determined by blinded independent radiology committee per RECIST v1.1 criteria.²

“Patients with mCRPC face a poor prognosis of less than two years, and many who progress on a novel hormonal therapy are seeking alternative treatment options to chemotherapy,” Vicki L. Goodman, MD, executive vice president, Product Development & Medical Affairs, and chief medical officer, Exelixis, said.¹ “We are pleased to report positive findings from the CONTACT-02 trial, in which cabozantinib in combination with an immune checkpoint inhibitor has demonstrated an efficacy benefit in another tumor type with significant unmet need. We look forward to discussing these findings with the US FDA and to presenting further details at an upcoming medical meeting.”

“With prostate cancer confirmed as the second most commonly occurring cancer in men globally, the need for innovative new therapies is extensive, especially for those whose cancer has progressed to the metastatic castration-resistant form,” Howard Mayer, executive vice president and head of Research and Development at Ipsen, added. “These results represent the first positive phase 3 data of its kind for a TKI 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.”

References

1. 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. News release. Exelixis, Inc. August 21, 2023. Accessed August 21, 2023. https://ir.exelixis.com/news-releases/news-release-details/exelixis-and-ipsen-announce-positive-results-phase-3-contact-02
2. Study of cabozantinib in combination with atezolizumab versus second NHT in subjects with mCRPC (CONTACT-02). ClinicalTrials.gov. Updated July 17, 2023. Accessed August 21, 2023. https://clinicaltrials.gov/study/NCT04446117