Kisqali (ribociclib)

P3, N=500, Not yet recruiting, AstraZeneca

P=N/A, N=550, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

P3, N=3100, Suspended, Novartis Pharmaceuticals | Recruiting --> Suspended

P3, N=500, Not yet recruiting, American Society of Clinical Oncology

P2, N=144, Recruiting, The First Affiliated Hospital with Nanjing Medical University

P1/2, N=18, Recruiting, Jonsson Comprehensive Cancer Center | Phase classification: P1b --> P1/2 | Trial completion date: Apr 2025 --> Apr 2026 | Trial primary completion date: Apr 2024 --> Apr 2025

The high-quality evidence from the BrasiLEEira study corroborates the RCTs' findings, expanding its validity to a broader spectrum and underrepresented population who may benefit from ribociclib treatment.

P2, N=100, Not yet recruiting, Nationwide Children's Hospital | Trial completion date: Jan 2034 --> May 2034 | Initiation date: Jan 2024 --> May 2024 | Trial primary completion date: Jan 2028 --> May 2028

This review provides key background information on the CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib. Additionally, special consideration should be given to populations at higher risk for polypharmacy, such as older patients with greater comorbidities. These interactions and patient characteristics should be considered when developing individual treatment plans with CDK4/6 inhibitors.

P2, N=90, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

We demonstrated for the first time that ribociclib serves as a novel PDE4 inhibitor for treating neutrophilic inflammation and ARDS. The repurposing ribociclib and targeting neutrophilic PDE4 offer a potential off-label alternative for treating lung lesions and other inflammatory conditions.

P1, N=48, Active, not recruiting, Nader Sanai | Trial completion date: Jan 2024 --> Jan 2025

P1/2, N=37, Recruiting, Kari Wisinski | Trial primary completion date: Jan 2024 --> May 2024

The prognostic value of HER2-low status remains controversial. Our study showed no significant effect of HER2 low expression on survival in patients receiving CDK 4/6i plus ET.

Ribociclib plus an NSAI significantly improved invasive disease-free survival among patients with HR-positive, HER2-negative stage II or III early breast cancer. (Funded by Novartis; NATALEE ClinicalTrials.gov number, NCT03701334.).

P=N/A, N=376, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting | Trial completion date: Jun 2025 --> Jun 2027 | Trial primary completion date: Jun 2025 --> Jun 2027

P1, N=68, Active, not recruiting, St. Jude Children's Research Hospital | Trial completion date: Mar 2025 --> May 2024

UM in this study was divided into three CNV subtypes, and a model based on eight aneuploidy score-related genes was established to evaluate the prognosis and drug treatment efficacy of UM patients. The current results may have the potential to help the clinical decision-making process for UM management.

In our study, we aimed to evaluate the effectiveness of palbociclib and ribociclib in first-line treatment in patients with premenopausal metastatic breast cancer and the effect of dose reduction due to neutropenia on progression-free survival...Liver metastasis, using a fulvestrant together with a CDK 4-6 inhibitor, ECOG PS 1 was found to be a negative prognostic factor...In our study, we found PFS over 27 months in patients diagnosed with premenopausal breast cancer with CDK 4-6 inhibitors used in first-line treatment, similar to post-menopausal patients. We did not detect any difference between the effectiveness of the two CDK 4-6 inhibitors, and we showed that there was no decrease in the effectiveness of the CDK 4-6 inhibitor in patients whose dose was reduced due to neutropenia.

P=N/A, N=2683, Active, not recruiting, Novartis Pharmaceuticals

P1/2, N=46, Completed, Sidney Kimmel Cancer Center at Thomas Jefferson University | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Sep 2023

Additionally, to enable simultaneous drug delivery and enhance synergistic antitumor efficacy, we developed a novel supramolecular nanodrug LEE011-FFERGD/CDDP, which was validated in an OSCC orthotopic mouse model. In summary, our study highlights the potential of a combined administration of CDK4/6 inhibitor and cisplatin as a promising therapeutic regimen for treating advanced or cisplatin resistant OSCC.

In a large real-world sample, more men with eBC are at clinical high risk according to the inclusion criteria of monarchE, NATALEE and OlympiA than would be expected in women. This is most likely due to more advanced stages at initial diagnosis in men. To evaluate whether CDK4/6 and PARP inhibitors improve prognosis also in men should be the topic of future real- world analyses.

P1/2, N=47, Recruiting, Pfizer | Phase classification: P1b/2 --> P1/2 | N=35 --> 47 | Trial completion date: Oct 2027 --> Dec 2026 | Trial primary completion date: Apr 2026 --> Dec 2026

P2; Trial completion date: Dec 2031 --> Apr 2032 | Trial primary completion date: Jun 2026 --> Apr 2027

Immunologically, ribociclib was associated with downregulated GES associated with APCs and the innate immune system in Luminal B tumors, contrary to existing preclinical data. Further studies are needed to understand the effect of CDK4/6 inhibition on the tumor cells and microenvironment, an effect which may vary according to tumor subtypes.

CDK4/6i received included 42/57 (73%) palbociclib, 14/57 (25%) ribociclib and 1/57 (2%) abemaciclib; 40/57 (70%) were in combination with an aromatase inhibitor and 17/57 (30%) with fulvestrant. Baseline methylation TF and ctDNA clearance as measured by GuardantINFINITY were prognostic in this cohort. Longitudinal sampling permitted genomic characterization and detection of alterations conferring acquired-resistance prior to clinical progression. Clinical correlates of ctDNA detection, clearance, and further serial genomic analyses will be presented.

CDK4/6 inhibitor LEE011 treatment alone may not be a suitable treatment option for lymphocytic leukemia; however, our findings in vitro support the combination of LEE011 with chemotherapy drugs to enhance anti-tumor activity in lymphocytic leukemia.

P1, N=396, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting

In conclusion, we developed a novel T cell exhaustion-associated signature, which holds considerable predictive value for both the prognosis of patients with HNSCC and the effectiveness of tumor immunotherapy.

Taken together, our study implicates CXCL1 as a critical role in ERBC growth and metastasis via crosstalk with fibroblast and cotargeting CXCR1/2 and CDK4/6 could potentially overcome endocrine resistant breast cancer.

Treatment of patients with visceral metastatic HR-positive, HER2-negative BC with ribociclib in combination with ET showed a tendency toward a more favorable clinical outcome. Despite small numbers of patients and sites, this head-to-head comparison with chemotherapy supports the use of ribociclib with ET in patients with visceral metastasis at risk of fast disease progression.

P3, N=3100, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

P1, N=265, Active, not recruiting, Relay Therapeutics, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Jan 2026 --> Jul 2024 | Trial primary completion date: Dec 2025 --> Jun 2024

P2, N=2, Completed, City of Hope Medical Center | Active, not recruiting --> Completed | Phase classification: P2a --> P2 | Trial completion date: Dec 2023 --> Jun 2023

P3, N=3100, Not yet recruiting, Novartis Pharmaceuticals | Trial primary completion date: Jul 2028 --> Sep 2029

P3, N=895, Recruiting, AstraZeneca | Trial completion date: Nov 2028 --> Aug 2029 | Trial primary completion date: Aug 2026 --> Nov 2027

P4, N=21, Terminated, Georgetown University | Trial completion date: Jul 2024 --> Oct 2023 | Active, not recruiting --> Terminated; Sufficient accrual into the African American/Black patient cohort and insufficient accrual into the NHW patient cohort.

P1, N=45, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Mar 2024 --> Sep 2024

P4, N=0, Withdrawn, University of Michigan Rogel Cancer Center | N=45 --> 0 | Not yet recruiting --> Withdrawn

P1/2, N=6, Active, not recruiting, Tvardi Therapeutics, Incorporated | Recruiting --> Active, not recruiting | N=53 --> 6 | Trial completion date: Feb 2025 --> Jun 2024 | Trial primary completion date: Dec 2024 --> Jun 2024

P3, N=287, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed