Cabozantinib plus nivolumab shows encouraging activity in mCRPC

The phase 2 CANOPY trial (NCT05502315) evaluating cabozantinib (Cabometyx) plus nivolumab (Opdivo) in patients with metastatic castration-resistant prostate cancer (mCRPC) met its prespecified interim efficacy threshold, demonstrating encouraging activity in this patient population. The study also reported a manageable safety profile with the combination, supporting progression to the second stage of the trial.

The results were presented at the 2026 American Association for Cancer Research Annual Meeting in San Diego, California.¹

The CANOPY trial is a prospective, multicenter, open-label, single-arm phase 2 study enrolling adult patients with progressive mCRPC according to Prostate Cancer Working Group 3 (PCWG3) criteria. Participants were enrolled through clinical trial sites across the US. Eligible patients were required to have prior exposure to at least 1 androgen receptor pathway inhibitor and an ECOG performance status of 2 or higher.² Prior taxane chemotherapy was permitted. Patients received cabozantinib 40 mg orally once daily plus nivolumab 480 mg intravenously every 4 weeks.

The primary end point was radiographic progression-free survival (rPFS) at 6 months by RECIST 1.1 and PCWG3 criteria. Investigators hypothesized that a 6-month rPFS rate greater than 30% would justify continued development. Under the interim design, at least 7 of the first 24 patients needed to remain progression-free at 6 months for the study to advance. Secondary end points included prostate-specific antigen (PSA) response, overall response rate, and safety.

Among the first-stage cohort, the median age was 71 years. Baseline disease characteristics reflected a heavily pretreated population: 66.7% had received prior chemotherapy and 25% had previously received lutetium Lu 177 vipivotide tetraxetan (¹⁷⁷Lu-PSMA-617; Pluvicto). Additionally, 50% of patients had de novo metastatic disease, 91.7% had bone metastases, 29.2% had bone-only disease, and 16.7% had visceral metastases.

Investigators reported that 8 patients remained progression-free at 6 months, meeting the criterion for continuation to stage 2. The median rPFS was 5.5 months (95% CI, >3.6 months). Among 17 evaluable patients, the objective response rate was 17.6%, corresponding to 3 confirmed responses. The median time to PSA progression was 1.87 months (95% CI, 1.81 to 3.78 months), with 1 patient achieving a PSA decline of at least 50%.

Grade 3 or higher treatment-related adverse events (AEs) occurred in 52% of patients, and 5 treatment-related serious AEs were reported. Common AEs included anorexia (58%), diarrhea (58%), fatigue (54%), nausea (46%), anemia (38%), aspartate aminotransferase increase (38%), alanine aminotransferase increase (33%), constipation (33%), and hypothyroidism (29%).

Based on these results, the CANOPY trial will proceed to stage 2 of the study protocol, which is expected to enroll an additional 23 patients. Final completion of the trial is anticipated for April 2027.²

REFERENCES

1. Panian J, Liu L, Pu M, et al. A phase 2 study of cabozantinib and nivolumab in metastatic castration resistant prostate cancer (CANOPY): Interim analysis. Presented at: 2026 American Association for Cancer Research Annual Meeting. April 17-22, 2026. San Diego, California. Abstract CT149
2. Study of cabozantinib and nivolumab in metastatic castration resistant prostate cancer (CANOPY). ClinicalTrials.gov. Last updated January 23, 2026. Accessed April 22, 2026. https://clinicaltrials.gov/study/NCT05502315