P1, N=66, Recruiting, Shenzhen Ionova Life Sciences Co., Ltd. | Not yet recruiting --> Recruiting

P1, N=14, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

P1, N=8, Completed, Merck Sharp & Dohme LLC | Recruiting --> Completed

P1, N=14, Not yet recruiting, Merck Sharp & Dohme LLC

P1, N=8, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

P1, N=66, Not yet recruiting, Shenzhen Ionova Life Sciences Co., Ltd.

P1, N=12, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

P1, N=8, Not yet recruiting, Merck Sharp & Dohme LLC

P1, N=14, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Oct 2027 --> Mar 2027 | Trial primary completion date: Apr 2026 --> Sep 2025

P1, N=12, Active, not recruiting, Merck Sharp & Dohme LLC

P1, N=14, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

53.0% and 36.8% had previously received both abiraterone and enzalutamide, and 69.7% and 64.7% had received cabazitaxel in patients with and without AR-LBD mutation respectively. Administration of Opevesostat to heavily pre-treated mCRPC patients shows promising antitumor activity. PSA50 responses were most frequent among patients harbouring activating AR-LBD mutations.

P1/2, N=220, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

P1, N=6, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

Additionally, in microsomes where N-acetylcysteine was used as a trapping agent, N-acetylcysteine conjugates (M3, M4, M5 and M6) of four isomeric O-quinone-derived reactive metabolites were found...The IC50 shift assay showed time-dependent inhibition of CYP3A4, 2C9, 2E1, 2C8 and 2D6 by PLG. This research contributes to the understanding of PLG-induced enzyme inhibition and bioactivation.

P1, N=14, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Feb 2026 --> Oct 2027 | Trial primary completion date: Oct 2025 --> Apr 2026

P1/2, N=220, Not yet recruiting, Merck Sharp & Dohme LLC

Agents targeting androgen biosynthesis can have systemic implications. Balancing management of prostate cancer with better understanding of the mechanisms associated with potential side effects will allow for patients to obtain improved antitumor benefit while mitigating against treatment-associated adverse effects.

In the Original Article, "Targeted Inhibition of CYP11A1 in Castration-Resistant Prostate Cancer", originally published December 26, 2023 (DOI: https://doi.org/10.1056/EVIDoa2300171), in the Abstract, under "Background", the sentence "ODM-208, a novel inhibitor of cytochrome P450 17A1 …" should have read "ODM-208, a novel inhibitor of cytochrome P450 11A1…" A corrected version of the article has been posted at evidence.nejm.org.

P1/2, N=38, Completed, Orion Corporation, Orion Pharma | Active, not recruiting --> Completed

P1/2, N=204, Active, not recruiting, Orion Corporation, Orion Pharma | Recruiting --> Active, not recruiting | Trial completion date: Sep 2024 --> Dec 2024 | Trial primary completion date: Sep 2024 --> Dec 2024

P1, N=14, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

P3, N=1200, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting | Trial completion date: Jun 2029 --> Aug 2028

P3, N=1500, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

53% and 33.8% of patients had previously received both abiraterone and enzalutamide, and 63.6% and 55.9% patients had received cabazitaxel in AR-LBD mutation positive and negative groups respectively. Administration of MK-5684 to heavily pre-treated mCRPC patients showed promising antitumor activity. PSA50 responses were most frequent among patients harboring activating AR-LBD mutations. Clinical trial information: NCT03436485.

P1, N=6, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

P1, N=14, Not yet recruiting, Merck Sharp & Dohme LLC

P3, N=1200, Not yet recruiting, Merck Sharp & Dohme LLC

P3, N=1500, Not yet recruiting, Merck Sharp & Dohme LLC

P1, N=6, Not yet recruiting, Merck Sharp & Dohme LLC

However, MBQ-168 is ~10X less potent than MBQ-167 at inhibiting CYP3A4, thus demonstrating its utility in relevant combination therapies. In conclusion, the MBQ-167 derivatives MBQ-168 and EHop-097 are additional promising anti metastatic cancer compounds with similar and distinct mechanisms.

Two early phase trials investigating CYP11A1 inhibitors - CYPIDES (ODM208, NCT03436485) and STESIDES (ODM209, NCT03878823) - recruited mCRPC patients with and without pre-specified AR LBD mutation...Overall, 212 (78%), 202 (74%), and 240 (88%) patients had received previous abiraterone, enzalutamide, and docetaxel respectively... AR LBD mutations were detected in ctDNA in 25% of men with advanced mCRPC treated with at least one ARSI. Their incidence was associated with a longer duration of treatment with enzalutamide and a longer time from CRPC and prostate cancer diagnosis. >

P1/2, N=38, Active, not recruiting, Orion Corporation, Orion Pharma | Trial completion date: Jan 2023 --> Oct 2023 | Trial primary completion date: Jan 2023 --> Oct 2023

P2, N=15, Recruiting, Hospital Universitario Dr. Jose E. Gonzalez

Rucaparib weakly increased systemic exposures of oral contraceptives and oral rosuvastatin and marginally increased the exposure of oral digoxin (a P-glycoprotein substrate). An exposure-response analysis revealed dose-dependent changes in selected clinical efficacy and safety endpoints. Overall, this article provides a comprehensive review of the clinical pharmacokinetics, pharmacodynamics, drug-drug interactions, effects of intrinsic and extrinsic factors, and exposure-response relationships of rucaparib.

In summary, HZ-L105 as a next generation Bcl-2 inhibitor, showed great potency on wild type and acquisition resistance mutations of Bcl-2 in vitro, excellent oral bioavailability, superior anti-tumor activities on preclinical xenograft model, and safety profiles,. It may provide new thoughts on treatment for a wide range of Bcl-2-dependent and Venetoclax-resistant hematological cancers.

In addition, combination treatment significantly enhanced the translocation of AIF to the nucleus in HeLa cells. In conclusion, the results demonstrate that the combination of TMS and nutlin-3a induces synergistic apoptosis in HeLa cells, suggesting the possibility that this combination can be applied as a novel therapeutic strategy for cervical cancer.

When assessing the effect of different inhibitors/inducers of metabolism, it was observed that metyrapone (a cytochrome P450 inhibitor) and phenobarbital (a cytochrome P450 inducer) slightly increased MTX cytotoxicity, while 1-aminobenzotriazole (a suicide cytochrome P450 inhibitor) decreased fairly the MTX-triggered cytotoxicity in differentiated AC16 cells. When focusing in autophagy, the mTOR inhibitor rapamycin and the autophagy inhibitor 3-methyladenine exacerbated the cytotoxicity caused by MTX and NAPHT, while the autophagy blocker, chloroquine, partially reduced the cytotoxicity of MTX...In conclusion, in our in vitro model, neither metabolism nor exogenously given NAPHT are major contributors to MTX toxicity as seen by the residual influence of metabolism modulators used on the observed cytotoxicity and by NAPHT's low cytotoxicity profile. Conversely, autophagy is involved in MTX-induced cytotoxicity and MTX seems to act as an autophagy inducer, possibly through p62/LC3-II involvement.

Data from this study demonstrated that capmatinib is a moderate CYP1A2 inhibitor. Capmatinib administration did not cause any clinically relevant changes in midazolam exposure.

Overall, the drug-drug interaction and safety profiles of trilaciclib in these studies support its continued use in patients with extensive-stage small-cell lung cancer.

51% patients had previously received both abiraterone and enzalutamide, and 65% patients both docetaxel and cabazitaxel. Conclusions Administration of ODM-208 to heavily pre-treated mCRPC patients with AR LBD mutation was highly effective in blocking the production of steroid hormones and showed promising antitumor activity. NCT03436485.