P2, N=976, Recruiting, MedSIR | Trial completion date: Dec 2028 --> Jun 2028 | Trial primary completion date: Dec 2028 --> Jun 2028

P1, N=10, Completed, Eli Lilly and Company | Active, not recruiting --> Completed | Trial completion date: Jul 2026 --> Jan 2026

Our study demonstrates that the CDK4/6 inhibitor Abemaciclib and the BRD4 inhibitor BQ0 exert a synergistic effect in inhibiting the proliferation of triple-negative breast cancer (TNBC) cells in vitro...The kinases selectivity experimental suggested that 7f15 is a pan-BET inhibitor. In summary, 7f15, hereby designated as KWZL-7f15, is a novel dual CDK6/BET inhibitor with promising therapeutic potential for the treatment of triple-negative breast cancer.

P2, N=40, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026

We specifically find that gBRCA2-associated tumours are uniquely predisposed to develop acquired RB1 loss-of-function alterations, resulting in poor outcomes on standard-of-care frontline CDK4/6 inhibitor (CDK4/6i) combinations...Our findings suggest that prioritizing PARP inhibition in gBRCA2 carriers may intercept RB1-loss trajectories and delay resistance. More broadly, we establish a predictive framework for forecasting drug-resistant trajectories based on pre-treatment allelic configuration and mutational signatures.

P2, N=43, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Jan 2027

P3, N=5101, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: May 2026 --> May 2030 | Trial primary completion date: May 2026 --> May 2030

P1, N=30, Not yet recruiting, Guizhou Provincial People's Hospital

P2, N=16, Enrolling by invitation, Fudan University

To investigate this, we developed a fundamental in vitro model of cell cycle arrest and reentry based on reversible CDK4/6 inhibition (CDK4/6i) with palbociclib, compatible with quantitative single-cell live-imaging of a knock-in endogenous HES1 reporter...Preventing this dip at the point of release, by inducibly sustaining HES1 with a Tet-On system, upregulated the cell cycle inhibitor p21, impeded cell cycle reentry and induced cell death. These findings suggest that manipulating HES1 dynamics could represent a promising therapeutic approach to prevent reactivation of dormant tumor cells.

Eligible subjects were enrolled in NSCLC or melanoma tumor-specific cohorts and treated with abemaciclib 200 mg twice daily (BID) monotherapy or 150 mg BID for NSCLC patients on concurrent pemetrexed or gemcitabine. Although abemaciclib can achieve therapeutic concentrations in brain metastases tissue, this study did not meet its primary endpoint. The limited clinical activity in this study suggests that further clinical trials should focus on the use of abemaciclib combination therapy.

Furthermore, it discusses the emerging resistance mechanisms to PI3K inhibition, mitigation of adverse effects, and future directions for inavolisib in personalized oncology. As studies continue to demonstrate its clinical utility, inavolisib exhibits preferential activity against the mutated PI3Kα isoform, thereby enhancing therapeutic specificity for combination therapy.