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Ribociclib

Ribociclib is a cyclin-dependent kinase (CDK) 4/6 inhibitor used in the treatment of hormone receptor-positive, HER2-negative advanced or metastatic breast cancer.
It works by blocking the activity of CDK4 and CDK6, which are involved in cell cycle progression, thereby inhibiting tumor growth.
Ribociclib has been shown to improve progression-free survival when used in combination with endocrine therapy.
Researchers can explore the latest Ribociclib research and protocols using PubCompare.ai's AI-powered platform, which enables intelligent comparisons across literature, preprints, and patents to enhance reproducibility and accuracy in their studies.

Most cited protocols related to «Ribociclib»

1
Costs of Metastatic Breast Cancer Treatments
Cited 7 times
Routine disease management costs, including hospitalizations, outpatient visits, and laboratory scans, were modeled using data from Xie et al. (2015) and applied monthly to the PF and PD states (Table 1).20 (link)Subsequent (second- and third-line) treatment costs were applied one-off at the start of the model evaluation. Not all patients were assumed to receive further treatment, and the case mix of subsequent therapies varied depending on whether a CDK 4/6 inhibitor was received at first line, to reflect the availability and expected use of palbociclib at second line after letrozole monotherapy. The use of a CDK 4/6 inhibitor after progression on a CDK 4/6 inhibitor at first line was not considered.
Total cost of subsequent treatment was calculated by multiplying the mean treatment duration in months by the monthly treatment cost and the market shares in a second-line or third-line setting. Market share and treatment data were sourced from Novartis, and the lowest WAC formulation on the market was used (data on file, Novartis, e-mail communications, 2016). Eribulin was chosen as a proxy representing all chemotherapies because it was the highest-cost first-line chemotherapy.
Mistry R., May J.R., Suri G., Young K., Brixner D., Oderda G., Biskupiak J., Tang D., Bhattacharyya S., Mishra D., Bhattacharyya D, & Dalal A.A. (2018). Cost-Effectiveness of Ribociclib plus Letrozole Versus Palbociclib plus Letrozole and Letrozole Monotherapy in the First-Line Treatment of Postmenopausal Women with HR+/HER2- Advanced or Metastatic Breast Cancer: A U.S. Payer Perspective. Journal of Managed Care & Specialty Pharmacy, 24(6), 10.18553/jmcp.2018.24.6.514.
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Publication 2018
Disease Progression eribulin Hospitalization Letrozole Outpatients palbociclib Patients Pharmacotherapy Radionuclide Imaging
2
In Vivo Validation of Targeted Therapies
Cited 6 times
The following reagents were used for in vivo validations upon randomization of tumor bearing NSG mice: MK-8669/Ridaforolimus as an allosteric mTORC1 inhibitor (1mg/kg, 5IW), BKM120/Buparlisib as a pan-PI3K and BYL719 and GDC0032/Taselisib as PI3K-alpha inhibitors (27.5, 35mg/kg 6IW and 5 mg/kg, respectively), LEE011/Ribociclib as a CDK4/6 inhibitor (75mg/kg), AZD2281 (Olaparib/Lynparza) as a PARP inhibitor (50mg/kg, 5IW), AZD1775 as Wee1 inhibitor (120mg/kg, 5dON 9dOFF) and Tamoxifen (10mg/ml, 100μl daily) as an ER pathway inhibitor. Tumor volumes were normalized to the starting tumor volume and mean volumes were plotted and compared to vehicle-treated controls. Details such as number of mice used and mean volumes per treatment arm are shown in Table S7.
All experimental procedures were approved by the University of Cambridge Animal Welfare and Ethical Review Committee and by the Vall d’Hebron Hospital Clinical Investigation Ethical Committee and Animal Use Committee.
Bruna A., Rueda O.M., Greenwood W., Batra A.S., Callari M., Batra R.N., Pogrebniak K., Sandoval J., Cassidy J.W., Tufegdzic-Vidakovic A., Sammut S.J., Jones L., Provenzano E., Baird R., Eirew P., Hadfield J., Eldridge M., McLaren-Douglas A., Barthorpe A., Lightfoot H., O’Connor M.J., Gray J., Cortes J., Baselga J., Marangoni E., Welm A.L., Aparicio S., Serra V., Garnett M.J, & Caldas C. (2016). A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds. Cell, 167(1), 260-274.e22.
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Publication 2016
Animals AZD-1775 AZD 2281 buparlisib BYL719 GDC-0032 inhibitors LEE011 Lynparza Mechanistic Target of Rapamycin Complex 1 MK 8669 Mus Neoplasms NVP-BKM120 olaparib PIK3CA protein, human PIK3CG protein, human Poly(ADP-ribose) Polymerase Inhibitors ribociclib ridaforolimus Tamoxifen taselisib
3
Utility-Based Economic Assessment of Treatments
Cited 5 times
Treatment effectiveness was measured in LYs calculated from survival projections and QALYs (calculated from the time spent in each state combined with health-state utility [HSU] values).
Utility values for PF with stable disease and PF with response were derived from EuroQol 5-dimension 5-level (EQ-5D-5L) data collected in MONALEESA-2, which were converted to HSUs using a published value set. Since a U.S. value set for the EQ-5D-5L was not available, HSUs were calculated using the latest UK value set.25 (link)Utility values for PD were obtained from the published literature because, in MONALEESA-2, EQ-5D-5L was collected up to only 1 month after progression, thereby limiting data capture to the immediate health consequences of PD. The study by Lloyd et al. (2006) was used; this study reported HSUs estimated via the standard gamble technique and has been used in previous economic studies.26 (link)Disutility values associated with AEs (i.e., the effects of AEs on HSU) were also sourced from the literature. Table 1 shows the HSU values applied to the PF and PD health states and the disutility values associated with AEs presented by AE and mean AE duration.27
Mistry R., May J.R., Suri G., Young K., Brixner D., Oderda G., Biskupiak J., Tang D., Bhattacharyya S., Mishra D., Bhattacharyya D, & Dalal A.A. (2018). Cost-Effectiveness of Ribociclib plus Letrozole Versus Palbociclib plus Letrozole and Letrozole Monotherapy in the First-Line Treatment of Postmenopausal Women with HR+/HER2- Advanced or Metastatic Breast Cancer: A U.S. Payer Perspective. Journal of Managed Care & Specialty Pharmacy, 24(6), 10.18553/jmcp.2018.24.6.514.
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Publication 2018
Disease Progression UK 25
4
Dose-Escalation Study of Ribociclib in Advanced Solid Tumors
Cited 4 times
This Phase I, open-label, dose-escalation study of single-agent ribociclib was undertaken in patients with Rb+ advanced solid tumors or lymphomas to determine the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) of ribociclib, and to characterize the dose-limiting toxicities (DLTs) associated with ribociclib. The study also aimed to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary activity of ribociclib in patients with solid tumors, including tumors that harbored aberrations in the cyclin D–CDK4/6–INK4–Rb pathway and other cancer-related genes.
Patients received escalating doses of oral ribociclib either on a 3-weeks-on/1-week-off schedule, or a continuous 28-day schedule until disease progression, unacceptable toxicity, death, or consent withdrawal. Ribociclib dose escalation (starting dose: 50 mg/day 3-weeks-on/1-week-off; selected based on 4-week preclinical studies) was guided by the adaptive Bayesian Logistic Regression Model (BLRM) including Escalation With Overdose Control (EWOC) principle (11 (link)). DLTs were evaluated during the first treatment cycle (28 days) and were defined according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. as adverse events (AEs) or clinically significant abnormal laboratory values suspected to be related to ribociclib treatment, which prevented the start of a new cycle of treatment within 7 days of the scheduled new cycle start date. In order to be eligible for a second or later cycle of treatment, patients were required to have had an absolute neutrophil count ≥1.0 × 109/L, platelet count ≥75.0 × 109/L, and no current non-hematologic toxicities ≥ CTCAE grade 2. Patients falling outside these criteria were deemed to have a DLT. DLTs also comprised: grade 4 neutropenia lasting ≥7 consecutive days; grade 4 thrombocytopenia; grade 3/4 neutropenia with fever (temperature ≥38.5°C); serum creatinine >2 ×upper limit of normal; grade ≥3 total bilirubin, or grade 2 total bilirubin with grade 2 increase in alanine transaminase (ALT), or aspartate aminotransferase; grade ≥3 ALT increase; QT corrected (QTc) interval ≥501 ms on ≥2 separate electrocardiograms; grade ≥3 nausea or vomiting despite optimal anti-emetic therapy; grade ≥3 diarrhea despite optimal antidiarrhea treatment; any grade 3/4 non-hematologic AE (including biochemical findings) except for brief (<72 hours) grade 3 fatigue; grade 3 alopecia, or grade 3 electrolyte disturbance (supplementation allowed) resolving to grade ≤1 within 7 days of drug interruption.
In order to declare a dose as the MTD, at least six evaluable patients must have been treated at that dose level. The starting dose for the continuous schedule was to be at least one dose level below the MTD established with the 3-weeks-on/1-week-off schedule, and was also determined by available safety and PK data. Upon determination of the MTD/RDE, an expansion phase sought to further evaluate the safety and tolerability, preliminary clinical activity, PK, and PD of ribociclib at the RDE.
Infante J.R., Cassier P.A., Gerecitano J.F., Witteveen P.O., Chugh R., Ribrag V., Chakraborty A., Matano A., Dobson J.R., Crystal A.S., Parasuraman S, & Shapiro G.I. (2016). A Phase I Study of the Cyclin-Dependent Kinase 4/6 Inhibitor Ribociclib (LEE011) in Patients With Advanced Solid Tumors and Lymphomas. Clinical cancer research : an official journal of the American Association for Cancer Research, 22(23), 5696-5705.
Publication 2016
5
Cost-Effectiveness Analysis of CDK 4/6 Inhibitors
Cited 4 times
The following model assumptions were made: (a) Patients received ribociclib plus letrozole or, in accordance with National Comprehensive Cancer Network guidelines, palbociclib plus letrozole or letrozole monotherapy; (b) all costs were applied to the mid-cycle occupancy to minimize under-or overestimation; (c) the cost of CDK 4/6 inhibitor therapy was modeled independently of PFS, based on MONALEESA-2 data showing that, on average, patients discontinue treatment before disease progression; (d) MONALEESA-2 and PALOMA-1 were considered equivalent, so that any difference in patient population had a minimal impact on outcomes; (e) subsequent treatment costs accrued at the start of the time horizon; (f) ribociclib plus letrozole and palbociclib plus letrozole were assumed to have had a clinical equivalence effect on OS and PFS, since the therapies share the same CDK 4/6 pathway inhibition mechanism; (g) proportional hazards between comparators held true (in the absence of patient-level data from other trials, it was challenging to reestimate the effect of treatment on a nonproportional hazards scale); (h) AEs occurred in the first month of the model, reflecting the likelihood that they would be experienced within the first year of therapy; and (i) HSUs were dependent on response status, as supported by the published literature.
Mistry R., May J.R., Suri G., Young K., Brixner D., Oderda G., Biskupiak J., Tang D., Bhattacharyya S., Mishra D., Bhattacharyya D, & Dalal A.A. (2018). Cost-Effectiveness of Ribociclib plus Letrozole Versus Palbociclib plus Letrozole and Letrozole Monotherapy in the First-Line Treatment of Postmenopausal Women with HR+/HER2- Advanced or Metastatic Breast Cancer: A U.S. Payer Perspective. Journal of Managed Care & Specialty Pharmacy, 24(6), 10.18553/jmcp.2018.24.6.514.
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Publication 2018
ARID1A protein, human Burkitt Leukemia Conditioning, Classical Disease Progression Letrozole Malignant Neoplasms palbociclib Patients Psychological Inhibition ribociclib Therapeutics

Most recents protocols related to «Ribociclib»

1
Combination Therapy Enhances Cancer Cell Killing
Not available on PMC !

Example 38

This experiment was to evaluate the effect of killing cancer cells by treating MDA-MB-231 cells (human breast cancer cells) with the test substance GI-101 alone or in combination with Ribociclib substance in an in vitro environment.

MDA-MB-231 cells were purchased from the Korea cell line bank and cultured in RPMI1640 medium (Gibco) containing 10% FBS (Gibco) and 1% antibiotic/antifungal agent (Gibco). For use in cancer cell killing test, the cells were harvested using trypsin (Gibco), and then suspended in RPMI1640 medium, and then dead cells and debris were removed using Ficoll (GE Healthcare Life Sciences) solution. The cells suspended in RPMI1640 medium were carefully layered on ficoll solution. The cell layer with a low specific gravity formed by centrifuging at room temperature at 350×g for 20 minutes was collected with a pipette, washed with PBS (Gibco), and then centrifuged at room temperature at 350×g for 5 minutes. The separated cell layer was made into a suspension of 2×105 cells/mL with FBS-free RPMI1640 medium. The cancer cell suspension was stained at 37° C. for 1 hour using CELLTRACKER™ Deep Red Dye (Thermo) in order to track proliferation of cancer cells or inhibition of the proliferation. After staining, it was centrifuged at 1300 rpm for 5 minutes, and then it was washed with FBS-free RPMI1640 medium, and then suspended in RPMI1640 medium containing 5% human AB serum (Sigma) to a concentration of 2×105 cells/mL. The cancer cell suspension was added to each well of a 96-well microplate (Corning) by 50 μl (1×104 cells), and then stabilized in an incubator (37° C., 5% CO2) for 1 hour.

Human peripheral blood mononuclear cells (PBMCs) were used in order to identify the effect of killing cancer cells by GI-101. The human PBMCs were purchased from Zen-Bio, and the PBMCs stored frozen were placed in a 37° C. water bath, and thawed as quickly as possible, and then transferred to RPMI1640 medium (Gibco) containing 10% FBS (Gibco) and 1% antibiotic/antifungal agent (Gibco), and centrifuged at 1300 rpm for 5 minutes. The separated cell layer was suspended in RPMI1640 medium, and then dead cells and debris were removed using Ficoll (GE Healthcare Life Sciences) solution in the same manner as the cancer cell line. The cells suspended in RPMI1640 medium were carefully layered on ficoll solution. The cell layer with a low specific gravity formed by centrifuging at room temperature at 350×g for 20 minutes was collected with a pipette, washed with PBS (Gibco), and then centrifuged at room temperature at 350×g for 5 minutes. The separated cell layer was suspended in RPMI1640 medium containing 5% human AB serum (Sigma) to a concentration of 5×105 cells/mL. The PBMC suspension was dispensed 50 μl into each well of a 96-well microplate (Corning) in which cancer cell line has been dispensed, depending on the conditions.

In order to identify the effect of killing the cells, a CytoTox Green reagent (INCUCYTE™ CytoTox Green, Satorius) that binds to the DNA of cells to be killed was prepared in 1 μl per 1 mL of RPMI1640 medium containing 5% human AB serum (Sigma). The prepared medium was used for dilution of the test substance, and the effect of killing the cells could be quantitatively identified by staining the cells to be killed when the test substance was co-cultured with cancer cell lines and PBMCs.

Ribociclib test substance was diluted using RPMI1640 medium containing a CytoTox Green reagent, and then used in the experiment at a final concentration of 913 nM (50 μl) per well of a 96-well microplate. GI-101 was diluted by ⅓ using RPMI1640 medium containing a CytoTox Green reagent, and then used in the experiment at a final concentration 100 nM by 50 μl per well of a 96-well microplate.

The prepared test substance was placed in each well of a 96-well microplate in which cancer cell lines and PBMCs were dispensed depending on the conditions, and cultured in an incubator (37° C., 5% CO2) for 24 hours, and the proliferation or death of cancer cells was observed through the real-time cell imaging analysis equipment IncuCyte S3 (Satorious). The death of cancer cells was quantified by the integrated intensity of the cells stained in green with a CytoTox Green reagent.

FIG. 126 illustrates the effect of killing cancer cells in a condition of GI-101 at 100 nM. In the case of co-culturing only cancer cells and PBMCs, the effect of killing cancer cells was identified, and tended to be higher than that of treatment with GI-101 alone. In the case of treatment with Ribociclib alone and treatment with a combination of GI-101+Ribociclib, an excellent effect of killing cancer cells was shown as compared with the case of co-culturing only cancer cells and PBMCs, and in the case of treatment with a combination of GI-101+Ribociclib, the most excellent effect of killing cancer cells was shown.

US11857601B2. Pharmaceutical composition for cancer treatment comprising fusion protein including IL-2 protein and CD80 protein and anticancer drug (2024-01-02). GI INNOVATION, INC. [KR]. Inventors: Myung Ho Jang [KR], Su Youn Nam [KR], Young Jun Koh [KR].
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Patent 2024
2
Pharmacokinetics of Ribociclib in Plasma
Serial whole blood samples for pharmacokinetic analysis of ribociclib were collected in two 2 mL EDTA tubes during the first cycle of treatment, 30 minutes before and 0.5, 1, 2, 4, 6, and 8 hours after administration of ribociclib on day 8 and day 14 of the first cycle of treatment. Plasma was isolated by centrifugation at 1,500 × g for 10 minutes within 30 minutes following blood collection and aliquots (2 ml each) were placed in ice immediately and then stored frozen at −70°C or below until analyzed. The plasma concentration of ribociclib was determined using a liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay. Quality assurance was maintained by injecting quality control samples each time patient samples were assayed.
Plasma concentration-time data were analyzed by standard non-compartmental methods using the program WinNonlin (Pharsight, Mountain View, CA). The areas under the plasma concentration time curve (AUC) on day 8 and day 14 were calculated by trapezoidal approximation. The accumulation ratio (R) was calculated as the ratio of day 14 AUC0–8h versus the day 8 AUC0–8h. The apparent elimination half-life (t1/2) was calculated as −(0.693*τ)/ln((R−1)/R) where R is accumulation ratio and τ is the dosing interval (24 hours). Since a 24-hour blood sample was not drawn on day 14, the 24-hour plasma concentration after ribociclib administration was estimated to be equivalent to the pre-dose concentration based on the assumption that steady-state was reached on day 14, and the AUC over the 24-hour dosing interval on day 14 (AUCt) was calculated by trapezoidal approximation. Oral steady-state clearance (CLSS/F) was calculated using the equation, CLSS/F = Dose/AUCt, where dose is the administered dose of ribociclib. Standard descriptive statistics were used to summarize plasma ribociclib PK parameters.
Seetharam M., Norman A., Allred J., Kong J., Opyrchal M., Ma W.W., Lou Y., Dy G.K., Mahipal A., Weroha J., Wahner-Hendrickson A., Reid J.M, & Adjei A.A. (2024). A Phase I Study of sequences of the CDK4/6 Inhibitor, Ribociclib Combined with Gemcitabine in Patients with Advanced Solid Tumors. Research Square.
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Publication Preprint 2024
3
Gemcitabine and Ribociclib Combination Therapy
Treatment cycles were 21 days in length. Gemcitabine was administered intravenously on cycle days 1 and 8 and ribociclib taken orally once daily on days 8–15, followed by a 7-day rest. In order to minimize the inter-patient variability of PK assessments, participants took their first cycle dose of ribociclib immediately before gemcitabine infusion on day 8. Novartis provided ribociclib. The initial cohort in the dose escalation phase started at Dose Level 1 and subsequent patient cohorts were enrolled based on the safety and tolerability of the preceding dose level cohort as outlined in Supplemental Table 1.
Adverse events (AE) were graded according to the National Cancer Institute Common Toxicity Criteria version 4 (NCI CTCAE v4.0). When patients experienced Grade 3 or Grade 4 treatment related toxicity or intolerable Grade 2 toxicity despite optimal supportive care, treatment might be delayed and/or dose reduced. In the event of multiple toxicities, dose modification was based on the worst toxicity observed. For any AE ≥ Grade 2, ribociclib was dose interrupted until recovery to Grade ≤ 1, except for Grade 2 anemia or neutropenia for which no dose adjustment was required. When a patient required dose modification of ribociclib due to protocol-guided AE, the dose was reduced by 200 mg per day. Ribociclib dose reductions to the next lower dose level were required if a patient experienced a recurrence of Grade 3 thrombocytopenia, a Grade 3 neutropenia that took > 7 days to resolve, first Grade 4 neutropenia, first Grade 3 febrile neutropenia, or any Grade 3 nonhematological AE. Ribociclib was discontinued if a patient developed a Grade 4 anemia, febrile neutropenia, or non-hematological toxicity. Gemcitabine was postponed on Day 1 without dose adjustment on resumption for thrombocytopenia with platelet count < 100 × 109/L until platelets recovered to above that threshold; neutropenia Grade 2/3 until recovery to ≤ Grade 1; anemia Grade 3 until recovery to Grade ≤ 2; and non-hematological AE Grade 2 until recovery to Grade ≤ 1. Gemcitabine was dose reduced after recovery from Grade 4 thrombocytopenia and neutropenia or Grade 3 febrile neutropenia. Gemcitabine was discontinued if a patient developed Grade 4 febrile neutropenia or anemia.
Seetharam M., Norman A., Allred J., Kong J., Opyrchal M., Ma W.W., Lou Y., Dy G.K., Mahipal A., Weroha J., Wahner-Hendrickson A., Reid J.M, & Adjei A.A. (2024). A Phase I Study of sequences of the CDK4/6 Inhibitor, Ribociclib Combined with Gemcitabine in Patients with Advanced Solid Tumors. Research Square.
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Publication Preprint 2024
4
Neoadjuvant Ribociclib-Letrozole vs Chemotherapy
The main results of the CORALLEEN neoadjuvant phase II study have been previously reported28 (link). This study is registered with ClinicalTrials.gov, number NCT03248427, and it is completed. The CORALLEEN trial was conducted under Good Clinical Practice guidelines and the Declaration of Helsinki, and the study protocol was approved by independent ethic committee of Hospital Vall d’Hebron. All patients provided written informed consent.
Briefly, postmenopausal women aged 18 years or older were accrued in this prospective, multicentric, randomized, parallel, non-comparative phase II clinical trial if they had an HR+/HER2− stage I-IIIA breast tumor with primary tumor size of at least 2 cm in diameter by magnetic resonance imaging (MRI) and a Prosigna®-defined Luminal B intrinsic subtype).
A total of 106 eligible patients were randomized in a 1:1 ratio to (A) ribociclib plus letrozole, or (B) multi-agent chemotherapy. Randomization was stratified based on tumor size (T3 vs. T1/T2) and nodal involvement (yes vs. no). Patients randomized to arm A received 28-day cycles of continuous daily letrozole, 2.5 mg per day, and ribociclib, 600 mg per day, according to a 3 weeks on/1 week off schedule, for a total duration of 24 weeks. Dose modifications were allowed to manage grade 2 or higher non-hematological adverse events and grade 3–4 hematological events. Two levels of dose reduction for ribociclib were prespecified: 400 mg/day on the first reduction and 200 mg/day on the second reduction. Patients discontinuing ribociclib treatment due to treatment-related toxicity could continue the active treatment phase of the study, receiving letrozole monotherapy as per the investigator’s discretion. Patients randomized to the standard chemotherapy arm received four cycles of doxorubicin 60 mg/m2, cyclophosphamide 600 mg/m2 administrated intravenously every 21 days, followed by weekly paclitaxel 80 mg/m2 intravenously for 12 weeks (AC-T). Surgery was done within 7 days after the last dose of ribociclib or 14 days after the last dose of chemotherapy. In the ribociclib plus letrozole group, letrozole was continued until the day of surgery. Tumor samples were collected according to protocol at baseline, day 14, and surgery, and subsequently formalin-fixed paraffin-embedded (FFPE).
Pascual T., Fernandez-Martinez A., Agrawal Y., Pfefferle A.D., Chic N., Brasó-Maristany F., Gonzàlez-Farré B., Paré L., Villacampa G., Saura C., Hernando C., Muñoz M., Galván P., Gonzàlez-Farré X., Oliveira M., Gil-Gil M., Ciruelos E., Villagrasa P., Gavilá J., Prat A, & Perou C.M. (2024). Cell-cycle inhibition and immune microenvironment in breast cancer treated with ribociclib and letrozole or chemotherapy. NPJ Breast Cancer, 10, 20.
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Publication 2024
5
Ribociclib and Gemcitabine Combination in Advanced Solid Tumors
The primary objectives were to describe the dose-limiting toxicities (DLT) and identify the MTD and recommended Phase II dose (RP2D) of the combination of ribociclib and gemcitabine in patients with advanced solid tumors. The MTD was defined as the maximum dose level at which ≤ 1/6 patients had DLT in the dose escalation phase. All patients who received the combination of study drugs within the first cycle were considered evaluable for toxicity.
DLT for this trial were defined as grade 4 neutropenia > 7 consecutive days; grade 4 thrombocytopenia or grade 3 with bleeding; grade 3 or 4 febrile neutropenia; QTc interval ≥ 501ms on ≥ 2 separate EKGs; cardiotoxicity or troponin ≥grade 3 or clinical signs of cardiac disease such as unstable angina or myocardial infarction; vomiting ≥ grade 3 over 48 hours despite optimal anti-emetic therapy; diarrhea ≥ grade 3 over 48 hours despite optimal anti-diarrheal therapy; bilirubin ≥ grade 2 for over 7 consecutive days or grade 3; ALT ≥grade 2 with a ≥grade 2 bilirubin elevation of any duration in absence of liver metastases, ALT≥ grade 3 for more than 4 consecutive days; grade 4 ALT or AST; grade 4 serum alkaline phosphatase >7 consecutive days; serum creatinine ≥grade 3; any non-hematologic events ≥grade 3 (excluding alopecia; grade 3 fatigue <5 days, grade 3 fever or infection without neutropenia < 5 days duration; grade 3 laboratory abnormalities responsive to oral supplementation or deemed by the investigator to be clinically insignificant). Persistent, intolerable treatment related toxicities which delayed treatment for >14 days, and failure to receive at least 80% of the scheduled doses due to treatment related toxicity (except when treatment delay is due to sub-optimally managed nausea, vomiting or diarrhea) were also considered DLT. If a patient did not have a DLT but could not complete at least 80% of ribociclib and 2 doses of gemcitabine, then they would be replaced. Safety evaluations were completed throughout the study and a follow-up safety evaluation included AE assessment and review of concomitant medications and occurred 30 days (+/− 3 days) after the last dose of study drug or until resolution of any drug related toxicities.
The secondary objectives were to describe pharmacokinetics, antitumor activity of the combination of ribociclib and gemcitabine, and correlative biomarker analysis. Secondary endpoints of efficacy included response rate (RR), progression free survival (PFS), and short-term survival. Tumors were measured at baseline and prior to or on Cycle 3 Day 1, then prior to or on Day 1 of every other cycle thereafter. RECIST 1.1 was used to assess and document RR in terms of complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). PFS was defined as time from enrollment to disease progression determined either clinically or radiographically. Three months after patients terminated treatment, follow-up short-term survival information was collected without further follow-up afterwards.
Seetharam M., Norman A., Allred J., Kong J., Opyrchal M., Ma W.W., Lou Y., Dy G.K., Mahipal A., Weroha J., Wahner-Hendrickson A., Reid J.M, & Adjei A.A. (2024). A Phase I Study of sequences of the CDK4/6 Inhibitor, Ribociclib Combined with Gemcitabine in Patients with Advanced Solid Tumors. Research Square.
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Publication Preprint 2024

Top products related to «Ribociclib»

1
Ribociclib by Selleck Chemicals
Sourced in United States
Ribociclib is a small molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6). It is used as a laboratory research tool to study cell cycle regulation and proliferation.
2
Palbociclib by Selleck Chemicals
Sourced in United States, Germany, United Kingdom, China
Palbociclib is a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6). It is a lab equipment product used for scientific research purposes.
3
Abemaciclib by Selleck Chemicals
Sourced in United States, Germany
Abemaciclib is a lab equipment product manufactured by Selleck Chemicals. It is a cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6) inhibitor.
4
Ribociclib by MedChemExpress
Sourced in United States
Ribociclib is a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. It functions by selectively inhibiting the activity of CDK4 and CDK6 enzymes, which are involved in the regulation of the cell cycle.
5
Ribociclib by Novartis
Sourced in Switzerland
Ribociclib is a laboratory instrument used for the detection and quantification of ribociclib, a cyclin-dependent kinase (CDK) 4 and 6 inhibitor. It is a key piece of equipment in the research and development of CDK 4/6 inhibitor-based therapies.
6
Abemaciclib by MedChemExpress
Sourced in United States, China
Abemaciclib is a small molecule inhibitor that selectively targets cyclin-dependent kinases 4 and 6 (CDK4 and CDK6). It is a laboratory reagent used in research settings.
7
Palbociclib by Merck Group
Sourced in United States, Germany, France
Palbociclib is a cyclin-dependent kinase (CDK) 4/6 inhibitor, a type of laboratory equipment used for cell cycle regulation research. It functions by selectively inhibiting the activity of CDK4 and CDK6, which are involved in the control of cell cycle progression.
8
Matrigel by BD
Sourced in United States, United Kingdom, Germany, China, Canada, Japan, Italy, France, Belgium, Australia, Uruguay, Switzerland, Israel, India, Spain, Morocco, Austria, Brazil, Ireland, Netherlands, Montenegro, Poland, Denmark
Matrigel is a solubilized basement membrane preparation extracted from the Engelbreth-Holm-Swarm (EHS) mouse sarcoma, a tumor rich in extracellular matrix proteins. It is widely used as a substrate for the in vitro cultivation of cells, particularly those that require a more physiologically relevant microenvironment for growth and differentiation.
9
Palbociclib by MedChemExpress
Sourced in United States, China
Palbociclib is a cyclin-dependent kinase (CDK) 4/6 inhibitor, a class of lab equipment used for in vitro studies.
10
Mcf 7 by American Type Culture Collection
Sourced in United States, United Kingdom, China, Germany, France, Japan, Italy, Switzerland, Sweden, India, Canada, Egypt, Australia, Holy See (Vatican City State), Brazil
MCF-7 is a cell line derived from human breast adenocarcinoma. It is an adherent epithelial cell line that can be used for in vitro studies.

More about "Ribociclib"

Ribociclib is a cyclin-dependent kinase (CDK) 4/6 inhibitor, a class of anti-cancer drugs that block the activity of CDK4 and CDK6 proteins.
These proteins are crucial for cell cycle progression, and by inhibiting them, Ribociclib can effectively slow down or halt the growth of hormone receptor-positive, HER2-negative advanced or metastatic breast cancer cells.
This selective CDK4/6 inhibitor has been shown to improve progression-free survival when used in combination with endocrine therapy, such as aromatase inhibitors or selective estrogen receptor modulators (SERMs).
Researchers can explore the latest Ribociclib research and protocols using PubCompare.ai's AI-powered platform, which enables intelligent comparisons across scientific literature, preprints, and patents to enhance the reproducibility and accuracy of their studies.
In addition to Ribociclib, other CDK4/6 inhibitors like Palbociclib and Abemaciclib have also been developed and approved for the treatment of hormone receptor-positive, HER2-negative advanced or metastatic breast cancer.
These drugs work in a similar manner, blocking the activity of CDK4 and CDK6 to inhibit tumor growth.
Researchers may also use in vitro models, such as the MCF-7 breast cancer cell line and Matrigel, to study the effects of Ribociclib and other CDK4/6 inhibitors on cancer cell proliferation, migration, and invasion.
By leveraging PubCompare.ai's cutting-edge technology, scientists can discover the optimal Ribociclib protocols and products to enhance the reproducibility and accuracy of their breast cancer research.