cabazitaxel

We report on the randomized portion of the phase 2, open-label CheckMate 650 trial (NCT02985957), in which docetaxel-experienced, biologically male patients with chemotherapy-refractory metastatic castration-resistant prostate cancer were randomized 2:2:1:2 to nivolumab 3 mg /kg plus ipilimumab 1 mg /kg (n = 73), nivolumab 1 mg /kg plus ipilimumab 3 mg /kg (n = 74), ipilimumab 3 mg /kg (n = 38), or cabazitaxel (n = 74). Preliminary post hoc biomarker analyses in patients who received treatment with any immunotherapy regimen (i.e., treated with either of the nivolumab plus ipilimumab regimens or with ipilimumab alone, n = 12) identified a transcriptional signature, derived from the most highly expressed genes across cell types within select perivascular immune niches (comprising CD31+ endothelial, CD14+HLA-DR+ myeloid, and CD4+ and CD8+ T cells), which was associated with prolonged overall survival. These results provide further evidence of antitumor activity with nivolumab plus ipilimumab in select patients with metastatic castration-resistant prostate cancer and nominate a candidate prognostic biomarker that warrants confirmation in future prospective clinical trials.

P3, N=675, Recruiting, Amgen | Active, not recruiting --> Recruiting

A combined ensemble binary classifier generated through XGBoost integrating these feature sets to predict docetaxel response outperformed models derived from any single feature set, achieving a training area-under-the-ROC curve of 0.87. Pre-cabazitaxel specimens, representing a docetaxel-resistant population, were used for external validation, with a concordance of 79.6% for predicting non-response.

Resistance to taxanes, such as docetaxel (Dtx) and cabazitaxel (Cbz), frequently emerges in castration resistant prostate cancer (CRPC). More importantly, NNMT-high patients were found to be non-responders to taxane-containing chemotherapy regimens. Collectively, our findings suggest that targeting NNMT and the pathways it affects, such as TGFβ, offers a viable approach for addressing taxane-resistant PC.

Despite it demonstrating efficacy in patients resistant to docetaxel and paclitaxel, two commonly used taxanes, and representing one of the second-line therapeutic options for patients with mCRPC, CBZ has limitations, including considerable side issues and reduced drug susceptibility that gradually emerge and constitute the primary cause of therapeutic failure. The resulting oxidative stress caused DNA damage and interference with mitotic spindle assembly, which induces cell cycle arrest and programmed cell death. These data indicate that AdoMet is capable of intensifying CBZ responsiveness in mCRPC cells, making the treatment more effective.

P1/2, N=30, Recruiting, M.D. Anderson Cancer Center | Suspended --> Recruiting

P1, N=300, Recruiting, Janssen Research & Development, LLC | Trial completion date: Sep 2027 --> May 2028 | Trial primary completion date: Jun 2026 --> Aug 2027

P3, N=195, Completed, Gustave Roussy, Cancer Campus, Grand Paris | Unknown status --> Completed

Cabazitaxel and carboplatin followed by abiraterone, together with ADT, was feasible, safe, and efficacious in patients with high-volume mCSPC, and warrants further study in larger randomized trials.

P3, N=675, Active, not recruiting, Amgen | Recruiting --> Active, not recruiting

The mGPS and PNI are useful prognostic indicators for risk stratification to predict survival in patients with castration-resistant prostate cancer treated with cabazitaxel.

P2, N=50, Recruiting, Wake Forest University Health Sciences | Trial completion date: Apr 2030 --> Mar 2028