abiraterone acetate

Androgen receptor (AR) signaling is the principal driver of prostate cancer, and drugs that target this pathway (e.g., abiraterone and enzalutamide) are standard treatments for metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer (mCRPC). These promising preclinical data supported clinical development of bavdegalutamide as a potential treatment for patients with prostate cancer. Bavdegalutamide was the first PROTAC protein degrader to enter human clinical trials, specifically in patients with mCRPC in a phase 1/2 study (NCT03888612).

P1, N=174, Recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Apr 2025 --> May 2029 | Trial primary completion date: Dec 2024 --> Aug 2025

P=N/A, N=24, Completed, UNC Lineberger Comprehensive Cancer Center | Recruiting --> Completed

We develop a custom targeted cfDNA sequencing assay, named AR-ctDETECT, to detect ctDNA in limiting plasma cfDNA available from mCRPC patients in the Alliance A031201 randomized phase 3 trial of enzalutamide with or without abiraterone. ctDNA-positive patients have significantly worse median overall survival than ctDNA-negative patients (29.0 months vs. 47.4 months, respectively). Here, we show that mCRPC patients identified as ctDNA-positive using the AR-ctDETECT assay have poor survival despite treatment with potent AR inhibitors in a phase 3 trial.

P2, N=58, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Dec 2030 --> Mar 2032 | Initiation date: Dec 2024 --> Mar 2025 | Trial primary completion date: Dec 2030 --> Mar 2031

P1/2, N=102, Terminated, Epizyme, Inc. | Active, not recruiting --> Terminated; Sponsor decision, no safety concern

Results suggest that TALA + ENZA may provide improvements in clinical outcomes relative to OLAP + AAP and NIRA + AAP in 1 L mCRPC; however, inherent limitations associated with the complexity of the analyses must be considered.

P2, N=23, Active, not recruiting, David Oh | Trial completion date: Oct 2024 --> Aug 2025 | Trial primary completion date: Oct 2024 --> Aug 2025

P3, N=696, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: May 2027 --> Nov 2027

P2, N=130, Completed, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School | Active, not recruiting --> Completed | Trial completion date: May 2025 --> Dec 2024

P=N/A, N=2903, Active, not recruiting, Pfizer | Completed --> Active, not recruiting | N=1800 --> 2903 | Trial completion date: Feb 2024 --> Jan 2025 | Trial primary completion date: Feb 2024 --> Jan 2025

P3, N=417, Recruiting, Hinova Pharmaceuticals Inc. | N=255 --> 417 | Trial primary completion date: Jun 2024 --> Dec 2024

P2, N=102, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2025 --> Feb 2026

P1, N=352, Recruiting, Ambrx, Inc. | N=262 --> 352 | Trial completion date: Mar 2027 --> Dec 2028 | Trial primary completion date: Dec 2025 --> May 2026

P1, N=19, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2024 --> Jul 2025

P=N/A, N=1000, Completed, Pfizer | Active, not recruiting --> Completed | Trial completion date: Oct 2024 --> Apr 2024 | Trial primary completion date: Oct 2024 --> Apr 2024

P2, N=53, Recruiting, Syntrix Biosystems, Inc. | Initiation date: Jun 2024 --> Nov 2024

P3, N=575, Active, not recruiting, Exelixis | Trial completion date: Aug 2024 --> Oct 2026

P2, N=132, Recruiting, University Health Network, Toronto | Active, not recruiting --> Recruiting | N=66 --> 132

P=N/A, N=42, Completed, Medical College of Wisconsin | Active, not recruiting --> Completed

P1, N=99, Recruiting, Endocyte | N=60 --> 99

Among men with mCRPC, there was a high burden of CHD, and higher leptin levels were associated with coronary atherosclerosis independently of traditional cardiac risk factors.

P2, N=54, Not yet recruiting, Zhejiang Provincial People's Hospital

Abiraterone combined with prednisone effectively relieves bone pain and improves PSA response rates in CRPC patients, suggesting benefits in enhancing quality of life and reducing testosterone levels without increasing adverse reactions. This therapy appears to have a safety profile comparable to that of conventional treatments.

In vivo experiments also revealed that combination therapy significantly inhibited tumour growth and reduced inducible expression of PPP1CA. PPP1CA is a key driver for abiraterone resistance, and nodularin-R enhances the anti-CRPC effects of abiraterone by inhibiting PPP1CA.

P3, N=675, Not yet recruiting, Amgen

D+T is active in mCRPC but patient selection remains a challenge. Further studies to develop predictive biomarkers are warranted.

P1/2, N=66, Not yet recruiting, Jiangsu HengRui Medicine Co., Ltd.

P2, N=60, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Sep 2024 --> Dec 2024

P1, N=18, Active, not recruiting, Washington University School of Medicine | Trial completion date: Mar 2026 --> Sep 2025

P1, N=99, Active, not recruiting, ESSA Pharmaceuticals | Recruiting --> Active, not recruiting | Trial completion date: Sep 2026 --> Jan 2025 | Trial primary completion date: Apr 2026 --> Oct 2024

P1, N=48, Completed, Sumitomo Pharma Switzerland GmbH | Active, not recruiting --> Completed | N=72 --> 48 | Trial completion date: May 2025 --> May 2024 | Trial primary completion date: May 2025 --> May 2024

P3, N=430, Recruiting, Telix Pharmaceuticals (Innovations) Pty Limited | Not yet recruiting --> Recruiting

Herein, we demonstrated the superior performance of ADT plus apalutamide in achieving pCR or MRD and in extending BCR duration among HRPC patients. Post-intervention pre-RP PSA content as well as genetic shifts, especially in the AR axis, are critical indicators of patient pathological and clinical outcomes. These findings highlight the significance of genetic testing and PSA content monitoring in treating HRPC patients.

There are subgroups of patients, such as those with low baseline cancer burden and PTEN/ERG wild-type status, more likely to achieve good response with nADT. In the case of long term oncological benefit to be proven, nADT might be an additional therapeutic resource for these patients.

P2, N=223, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Trial primary completion date: Dec 2024 --> Mar 2025

P3, N=439, Active, not recruiting, Curium US LLC | Trial completion date: Jun 2029 --> Feb 2029

These algorithms are intended to provide practical assistance to Canadian clinicians managing the most common AEs encountered with the novel combination, niraparib/AA+P, for mCRPC.

P2, N=200, Recruiting, Fudan University

P=N/A, N=152, Not yet recruiting, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

P2, N=0, Withdrawn, M.D. Anderson Cancer Center | Active, not recruiting --> Withdrawn

P3, N=72, Not yet recruiting, Emory University