A Phase 3 interventional study of Ribociclib and Letrozole in Breast Cancer, sponsored by Novartis Pharmaceuticals. Terminated at 41 sites in Italy. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-10.
Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 3, Interventional, and Treatment
Among 70 studies testing ribociclib in Breast Neoplasms — 17 open to participants now, 31 under way, 8 of them phase 3. ribociclib · Breast Neoplasms.
Among the 70 studies testing ribociclib in Breast Neoplasms, this one is the 20th largest by enrollment, is one of 8 that started in 2018, is one of 19 in phase 3, and was the 27th registered.
14,829 studies on the registry are indexed under Breast Neoplasms; 3,318 are open to participants now.
Browse Breast Neoplasms studies →17 of the 70 studies testing ribociclib in Breast Neoplasms are open now, in 11 countries. Recruiting first, the newest first:
Natera, Inc. · Sites in United States
Ages 18+
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University · Sites in China
Ages 18+ · Women only
Nagoya City University · Sites in Japan
Ages 18+
American Society of Clinical Oncology · Sites in United States
Ages 60+
H. Lee Moffitt Cancer Center and Research Institute · Sites in United States
Ages 18+ · Women only
By country, each count listing its studies:
ribociclib: first FDA approval 2017 (KISQALI), first EMA approval 2017. What it is approved for, and how studies give it, is on its page →
Of the 2,398 Breast Neoplasms studies recruiting now, 1,569 (65%) set no upper age limit and 592 (25%) stop at 75 or younger; 103 take children under 18; 215 take healthy volunteers.
This study: 18 Years and older · female · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
On this site’s reading of the record, ribociclib is the treatment under test here. Read study by study →
70 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 16 · Phase 2 34 · Phase 3 19 · Phase 4 5
First in 2013; this study’s year is marked. 8 started in 2018.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 287 is above the median of 72 across 10,900 interventional studies indexed under Breast Neoplasms.
Median enrollment 116 across the 70 interventional studies. Of the 34 that completed or were terminated, 19 (56%) have results posted.
This tab as a report to print or save as PDF → With an account.
24 of 70 have an industry lead sponsor. The 10 most frequent:
This study is registered under Novartis Pharmaceuticals, one of the names counted as Novartis. Under that name alone:
Novartis Pharmaceuticals is the lead sponsor of 2,718 studies on the registry; 221 are open to participants now.
Of its 585 completed or terminated interventional studies of FDA-regulated products, 438 (75%) have results posted.
199 studies in Breast Neoplasms by Novartis: 16 open now, 30 under way, 4 of them phase 3. Of 160 finished, 74 (46%) have results posted.
Among the 199 studies in Breast Neoplasms by Novartis, this one is the 41st largest by enrollment of the 155 interventional ones that give a count, is one of 5 that started in 2018, is one of 45 in phase 3, and was the 134th registered.
Novartis’s Breast Neoplasms studies by the year they started, since 1998.
7 of the studies testing ribociclib in Breast Neoplasms that are under way reach primary completion within a year, 1 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT04055493Phase 3Women's Cancer Study Group GmbHAdj. Marker-adjusted Personalized Therapy Comparing ET+Ribociclib vs Chemotherapy in Intermediate Risk, HR+/HER2- EBC | 2027-07-31 |
| NCT07130643Xinhong Wu, PhDEfficacy and Safety of CDK4/6 Inhibitors Combined With Endocrine Therapy in HR+/HER2- Neoadjuvant Therapy for Early Breast Cancer | 2026-12-20 |
| NCT06481956Zheng YabingT-DM1 Combined With CDK4/6 Inhibitor Ribociclib | 2027-01-10 |
| NCT05996107University of Michigan Rogel Cancer CenterStudy of Ribociclib Administered Concurrently With Postoperative Radiation Therapy in Patients With High-Risk, HR+/HER2- Breast Cancer | 2027-02 |
| NCT01872260Novartis PharmaceuticalsStudy of LEE011, BYL719 and Letrozole in Advanced ER+ Breast Cancer | 2027-02-26 |
Add all 7 to your calendar (.ics) → With an account.
Among the 70 studies testing ribociclib in Breast Neoplasms, from their registry updates:
Among Novartis’s 199 in Breast Neoplasms:
This tab as a report to print or save as PDF → With an account.
The purpose of this clinical trial is to study of the molecular features of postmenopausal women with hormone receptor-positive (HR+) HER2-negative advanced breast cancer on first-line treatment with ribociclib and letrozole and, in patients with a PIK3CA mutation, on second-line treatment with alpelisib plus fulvestrant
The main purpose of this local, multicenter study is to investigate genetic and gene expression alterations in tumor prior to and following progression on ribociclib, during core phase and then prior to and following progression on alpelisib and thus identify patterns of mutations, how they evolve, and their association with CDK4/6 inhibition and outcomes such as sustained response or early progression. The study also aims to evaluate pharmacogenomics and its association with adverse events (frequency and severity), drug-drug interactions and clinical outcomes.
Finally, the study will also generate additional long-term safety and efficacy data in this specific Italian population.
CORE PHASE Inclusion Criteria:
CORE PHASE Exclusion Criteria:
Note:
Patients who received neo/ therapy for breast cancer are eligible. If the prior neo/adjuvant therapy included letrozole or anastrozole, the disease-free interval must be greater than 12 months from the completion of treatment until study entry.
- Patient is currently using other anti-cancer therapy. Other protocol-defined inclusion/exclusion criteria may apply.
EXTENSION PHASE Inclusion criteria:
EXTENSION PHASE Exclusion criteria:
All drugs with overlapping toxicities must be discontinued within 7 days and AE resolved to v4.03 Grade ≤1 prior to study treatment. Exception to this criterion: patients with any grade of alopecia are allowed to enter the study.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HER2
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ribociclib oral (3weeks on/1week off) in combination with oral once daily letrozole: 600mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
Drug: Ribociclib · Drug: Letrozole
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28 days cycle
Drug: Alpelisib · Drug: Fulvestrant
Ribociclib oral (3weeks on/1week off) in combination with oral once daily letrozole: 600mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
Also known as: LEE011
Ribociclib oral (3weeks on/1week off) in combination with oral once daily letrozole: 600mg tablets ribociclib QD + 2.5 mg tablets letrozole QD
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28 days cycle
Also known as: BYL719
Alpelisib 300 mg oral daily on a continuous dosing schedule in combination with fulvestrant 500 mg intramuscular on Days 1 and 15 of Cycle 1, and on Day 1 of each cycle thereafter in a 28 days cycle
Progression-Free Survival (PFS) by Cycle 1 Day 15 Complete Mutational Dynamic Change
PFS: Time (months) from start of the study treatment to first documented progression or death due to any cause, whichever came first. Kaplan-Meier estimates. Persistent Wild Type: Wild Type (or single nucleotide polymorphisms \[SNPs\] only) at screening without hotspot mutations at any later assessment. Confirmed cleared: Mutated, with 100% decrease in target mutation variant allele frequency (VAF) at C1D15 or at C2D1 also observed at FI. Unconfirmed cleared: Mutated that cleared or at C1D15 or at C2D1 that were not cleared at FI. Late cleared: Mutated without 100% decrease in target mutation VAF at C1D15 and at C2D1 with 100% decrease in target mutation VAF at FI. New mutated: Wild Type ( \[SNPs\] only) at screening with hotspot mutations at C1D15 or C2D1. Late mutated: Wild Type patients (or SNPs only) at screening without hotspot mutations at C1D15 and C2D1 with hotspot mutations at FI. Confirmed mutated: Mutated without 100% decrease in target mutation VAF at any later assessment.
Time frame: Up to approximately 5.7 years
Number of Participants With Progression-Free Survival (PFS) Events by Cycle 1 Day 15 Complete Mutational Dynamic Change
Kaplan-Meier estimates. Persistent Wild Type: Wild Type (or single nucleotide polymorphisms \[SNPs\] only) at screening without hotspot mutations at any later assessment. Confirmed cleared: Mutated, with 100% decrease in target mutation variant allele frequency (VAF) at C1D15 or at C2D1 also observed at FI. Unconfirmed cleared: Mutated that cleared or at C1D15 or at C2D1 that were not cleared at FI. Late cleared: Mutated without 100% decrease in target mutation VAF at C1D15 and at C2D1 with 100% decrease in target mutation VAF at FI. New mutated: Wild Type ( \[SNPs\] only) at screening with hotspot mutations at C1D15 or C2D1. Late mutated: Wild Type patients (or SNPs only) at screening without hotspot mutations at C1D15 and C2D1 with hotspot mutations at FI. Confirmed mutated: Mutated without 100% decrease in target mutation VAF at any later assessment.
Time frame: Up to approximately 5.7 years
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. The data row labels below refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
Time frame: Up to approximately 5.7 years
Percent Change From Screening in Target Mutation Variant Allele Frequency (VAF)
The target mutation was defined as the hotspot mutation with the highest molecular frequency observed at screening excluding single nucleotide polymorphisms (SNPs, i.e., hotspot mutations observed at all timepoints with a minimum molecular frequency value of 30% and a variation coefficient greater than 0.15). The molecular frequency of target mutation at performed assessments during which the target mutation was not detected was assumed to be equal to 0%.
Time frame: Up to approximately 5.7 years
Number of Participants With Partial Response (PR) in the Extension Phase
PR was assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1, criteria and was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the screening sum of diameters.
Time frame: Up to approximately 1.6 years
Percent Change From Screening in Thymidine Kinase 1 (TK1) Serum Level
Time frame: Up to approximately 5.7 years
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. Data row labels refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
Time frame: Up to approximately 5.7 years
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. Data row labels refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
Time frame: Up to approximately 5.7 years
Percent Change From Screening in Target Mutation Molecular Frequency (VAF) for Long Responders
The target mutation was defined as the hotspot mutation with the highest molecular frequency observed at screening excluding single nucleotide polymorphisms (SNPs, i.e., hotspot mutations observed at all timepoints with a minimum molecular frequency value of 30% and a variation coefficient greater than 0.15). The molecular frequency of target mutation at performed assessments during which the target mutation was not detected was assumed to be equal to 0%.
Time frame: Up to approximately 5.7 years
Percent Change From Screening in Target Mutation Molecular Frequency (VAF) for Early Progressors
The target mutation was defined as the hotspot mutation with the highest molecular frequency observed at screening excluding single nucleotide polymorphisms (SNPs, i.e., hotspot mutations observed at all timepoints with a minimum molecular frequency value of 30% and a variation coefficient greater than 0.15). The molecular frequency of target mutation at performed assessments during which the target mutation was not detected was assumed to be equal to 0%.
Time frame: Up to approximately 5.7 years
Number of Screening Hotspot Mutations Per De Novo Patient in Liquid Biopsy Samples and Tissue Samples
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. Data row labels refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
Time frame: Up to approximately 5.7 years
Number of Screening Hotspot Mutations Per Recurrent Patient in Liquid Biopsy Samples and Tissue Samples
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. Data row labels refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
Time frame: Up to approximately 5.7 years
Overall Number of Evaluations of Hotspot Mutations and Non-hotspot Mutations Present in Both Liquid Biopsies and Tissue Samples at Screening
Results data refer to the total number of evaluations (i.e. the number of participants in the biomarker analysis set with both valid baseline liquid biopsy and tissue sample multiplied by 39 considered genes).
Time frame: Up to approximately 5.7 years
Overall Number of Evaluations of Hotspot Mutations and Non-hotspot Mutations Present in Both Liquid Biopsies and Tissue Samples at End of Treatment
Results data refer to the total number of evaluations (i.e. the number of participants in the biomarker analysis set with both valid baseline liquid biopsy and tissue sample multiplied by 39 considered genes).
Time frame: Up to approximately 5.7 years
Time to Progression (TTP)
Time to progression (TTP) was defined as time from date of start of treatment to the date of event defined as the first documented progression or death due to underlying cancer.
Time frame: Core phase: up to approximately 5.7 years. Extension phase: up to approximately 1.6 years
Percentage of Participants With Best Overall Response Rate of Complete Response (CR) or Partial Response (PR)
ORR was defined as the percentage of participants with a best overall response defined as complete response (CR) or partial response (PR): (CR+PR) per Response Evaluation Criteria in Solid Tumors (RECIST), v. 1.1. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time frame: Core phase: up to approximately 5.7 years. Extension phase: up to approximately 1.6 years
Percentage of Participants With Clinical Benefit Rate
Clinical benefit rate (CBR) was defined as the percentage of participants with a best overall response of complete response (CR), or partial response (PR) or an overall lesion response of stable disease (SD), lasting as per local review, for a duration of at least 24 weeks. Per RECIST v. 1.1, CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter since the treatment started.
Time frame: Core phase: up to approximately 5.7 years. Extension phase: up to approximately 1.6 years
Change From Baseline Tumor Mutational Burden (TMB) to Progression of Disease During the Core and Extension Phases
Time frame: Up to approximately 5.7 years
Change From Baseline Tumor Microenvironment Parameters to Progression of Disease During the Core and Extension Phases
Time frame: Up to approximately 5.7 years
| Milestone | Ribociclib+Letrozole (Core Phase) | Alpelisib+Fulvestrant (Extension Phase) |
|---|---|---|
| Started | 287 | 0 |
| Completed | 184 | 0 |
| Not completed | 103 | 0 |
| Withdrew: Death | 27 | 0 |
| Withdrew: Lost to follow-up | 14 | 0 |
| Withdrew: Other | 2 | 0 |
| Withdrew: Study terminated by sponsor | 45 | 0 |
| Withdrew: Subject/guardian decision | 15 | 0 |
| Milestone | Ribociclib+Letrozole (Core Phase) | Alpelisib+Fulvestrant (Extension Phase) |
|---|---|---|
| Started | 0 | 21 |
| Completed | 0 | 16 |
| Not completed | 0 | 5 |
| Withdrew: Death | 0 | 3 |
| Withdrew: Lost to follow-up | 0 | 1 |
| Withdrew: Subject/guardian decision | 0 | 1 |
PFS: Time (months) from start of the study treatment to first documented progression or death due to any cause, whichever came first. Kaplan-Meier estimates. Persistent Wild Type: Wild Type (or single nucleotide polymorphisms \[SNPs\] only) at screening without hotspot mutations at any later assessment. Confirmed cleared: Mutated, with 100% decrease in target mutation variant allele frequency (VAF) at C1D15 or at C2D1 also observed at FI. Unconfirmed cleared: Mutated that cleared or at C1D15 or at C2D1 that were not cleared at FI. Late cleared: Mutated without 100% decrease in target mutation VAF at C1D15 and at C2D1 with 100% decrease in target mutation VAF at FI. New mutated: Wild Type ( \[SNPs\] only) at screening with hotspot mutations at C1D15 or C2D1. Late mutated: Wild Type patients (or SNPs only) at screening without hotspot mutations at C1D15 and C2D1 with hotspot mutations at FI. Confirmed mutated: Mutated without 100% decrease in target mutation VAF at any later assessment.
| months | Ribociclib+Letrozole (Core Phase) |
|---|---|
| Persistent Wild Type n=76 | 55.82 (39.06 to NA) |
| New Mutated n=19 | 16.53 (9.03 to 45.90) |
| Late Mutated n=8 | 15.67 (2.00 to 21.42) |
| Confirmed Cleared n=46 | 22.44 (15.93 to 32.23) |
| Unconfirmed Cleared n=8 | 10.22 (2.69 to NA) |
| Late Cleared n=12 | 11.07 (3.29 to 19.09) |
| Confirmed Mutated n=18 | 14.32 (2.89 to 44.22) |
Kaplan-Meier estimates. Persistent Wild Type: Wild Type (or single nucleotide polymorphisms \[SNPs\] only) at screening without hotspot mutations at any later assessment. Confirmed cleared: Mutated, with 100% decrease in target mutation variant allele frequency (VAF) at C1D15 or at C2D1 also observed at FI. Unconfirmed cleared: Mutated that cleared or at C1D15 or at C2D1 that were not cleared at FI. Late cleared: Mutated without 100% decrease in target mutation VAF at C1D15 and at C2D1 with 100% decrease in target mutation VAF at FI. New mutated: Wild Type ( \[SNPs\] only) at screening with hotspot mutations at C1D15 or C2D1. Late mutated: Wild Type patients (or SNPs only) at screening without hotspot mutations at C1D15 and C2D1 with hotspot mutations at FI. Confirmed mutated: Mutated without 100% decrease in target mutation VAF at any later assessment.
| participants | Ribociclib+Letrozole (Core Phase) |
|---|---|
| Persistent Wild Type n=76 | 31 |
| New Mutated n=19 | 13 |
| Late Mutated n=8 | 6 |
| Confirmed Cleared n=46 | 28 |
| Unconfirmed Cleared n=8 | 6 |
| Late Cleared n=12 | 10 |
| Confirmed Mutated n=18 | 12 |
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. The data row labels below refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
| participants | Ribociclib+Letrozole (Core Phase) |
|---|---|
| None at Screening n=263 | 145 |
| None at Cycle 1 Day 15 n=238 | 152 |
| None at Cycle 2 Day 1 n=242 | 160 |
| None at First Imaging Evaluation n=206 | 147 |
| None at End of Study Treatment due to PD n=118 | 50 |
| None at End of Study Treatment due to Other n=39 | 27 |
| One at Screening n=263 | 70 |
| One at Cycle 1 Day 15 n=238 | 51 |
| One at Cycle 2 Day 1 n=242 | 53 |
| One at First Imaging Evaluation n=206 | 40 |
| One at End of Study Treatment due to PD n=118 | 26 |
| One at End of Study Treatment due to Other n=39 | 10 |
| Two at Screening n=263 | 32 |
| Two at Cycle 1 Day 15 n=238 | 28 |
| Two at Cycle 2 Day 1 n=242 | 21 |
| Two at First Imaging Evaluation n=206 | 11 |
| Two at End of Study Treatment due to PD n=118 | 21 |
| Two at End of Study Treatment due to Other n=39 | 2 |
| Three or More at Screening n=263 | 16 |
| Three or More at Cycle 1 Day 15 n=238 | 7 |
| Three or More at Cycle 2 Day 1 n=242 | 8 |
| Three or More at First Imaging Evaluation n=206 | 8 |
| Three or More at End of Study Treatment due to PD n=118 | 21 |
| Three or More at End of Study Treatment due to Other n=39 | 0 |
The target mutation was defined as the hotspot mutation with the highest molecular frequency observed at screening excluding single nucleotide polymorphisms (SNPs, i.e., hotspot mutations observed at all timepoints with a minimum molecular frequency value of 30% and a variation coefficient greater than 0.15). The molecular frequency of target mutation at performed assessments during which the target mutation was not detected was assumed to be equal to 0%.
| percent change | Ribociclib+Letrozole (Core Phase) |
|---|---|
| Cycle 1, Day 15 n=104 | -94.33 (-100.0 to 134.5) |
| Cycle 2, Day 1 n=106 | -100.00 (-100.0 to 167.8) |
| First Imaging Evaluation n=90 | -100.00 (-100.0 to 1110.9) |
| End of Treatment due to PD n=66 | -47.48 (-100.0 to 1133.9) |
| End of treatment due to other n=16 | -100.00 (-100.0 to 29.8) |
PR was assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1, criteria and was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the screening sum of diameters.
| participants | Alpelisib+Fulvestrant (Extension Phase) |
|---|---|
| Number of Participants With Partial Response (PR) in the Extension Phase | 3 |
| percent change | Ribociclib+Letrozole (Core Phase) |
|---|---|
| Cycle 1, Day 15 n=245 | -73.2 (-99 to 2370) |
| Cycle 2, Day 1 n=241 | -39.3 (-96 to 1378) |
| First Imaging Evaluation n=208 | -46.9 (-99 to 1604) |
| End of Treatment due to PD n=89 | 56.5 (-98 to 10033) |
| End of treatment due to other n=35 | 28.5 (-92 to 109213) |
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. Data row labels refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
| participants | Ribociclib+Letrozole (Core Phase) |
|---|---|
| None at Screening n=95 | 64 |
| None at Cycle 1 Day 15 n=84 | 60 |
| None at Cycle 2, Day 1 n=91 | 67 |
| None at First Imaging Evaluation n=82 | 66 |
| None at End of Study Treatment due to PD n=27 | 14 |
| None at End of Study Treatment due to Other n=4 | 1 |
| One at Screening n=95 | 23 |
| One at Cycle 1 Day 15 n=84 | 18 |
| One at Cycle 2, Day 1 n=91 | 22 |
| One at First Imaging Evaluation n=82 | 14 |
| One at End of Study Treatment due to PD n=27 | 7 |
| One at End of Study Treatment due to Other n=4 | 3 |
| Two at Screening n=95 | 4 |
| Two at Cycle 1 Day 15 n=84 | 4 |
| Two at Cycle 2, Day 1 n=91 | 2 |
| Two at First Imaging Evaluation n=82 | 2 |
| Two at End of Study Treatment due to PD n=27 | 2 |
| Two at End of Study Treatment due to Other n=4 | 0 |
| Three or More at Screening n=95 | 4 |
| Three or More at Cycle 1 Day 15 n=84 | 2 |
| Three or More at Cycle 2, Day 1 n=91 | 0 |
| Three or More at First Imaging Evaluation n=82 | 0 |
| Three or More at End of Study Treatment due to PD n=27 | 4 |
| Three or More at End of Study Treatment due to Other n=4 | 0 |
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. Data row labels refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
| participants | Ribociclib+Letrozole (Core Phase) |
|---|---|
| None at Screening n=21 | 8 |
| None at Cycle 1 Day 15 n=19 | 7 |
| None at Cycle 2, Day 1 n=21 | 9 |
| None at First Imaging Evaluation n=19 | 9 |
| None at End of Study Treatment due to PD n=20 | 7 |
| One at Screening n=21 | 5 |
| One at Cycle 1 Day 15 n=19 | 3 |
| One at Cycle 2, Day 1 n=21 | 3 |
| One at First Imaging Evaluation n=19 | 3 |
| One at End of Study Treatment due to PD n=20 | 4 |
| Two at Screening n=21 | 5 |
| Two at Cycle 1 Day 15 n=19 | 8 |
| Two at Cycle 2, Day 1 n=21 | 5 |
| Two at First Imaging Evaluation n=19 | 5 |
| Two at End of Study Treatment due to PD n=20 | 5 |
| Three or More at Screening n=21 | 3 |
| Three or More at Cycle 1 Day 15 n=19 | 1 |
| Three or More at Cycle 2, Day 1 n=21 | 4 |
| Three or More at First Imaging Evaluation n=19 | 2 |
| Three or More at End of Study Treatment due to PD n=20 | 4 |
The target mutation was defined as the hotspot mutation with the highest molecular frequency observed at screening excluding single nucleotide polymorphisms (SNPs, i.e., hotspot mutations observed at all timepoints with a minimum molecular frequency value of 30% and a variation coefficient greater than 0.15). The molecular frequency of target mutation at performed assessments during which the target mutation was not detected was assumed to be equal to 0%.
| percent change | Ribociclib+Letrozole (Core Phase) |
|---|---|
| Cycle 1, Day 15 n=26 | -98.82 (-100.0 to 101.6) |
| Cycle 2, Day 1 n=27 | -100.00 (-100.0 to 88.8) |
| First Imaging Evaluation n=23 | -100.00 (-100.0 to 40.5) |
| End of Treatment due to PD n=12 | -52.93 (-100.0 to 319.7) |
| End of treatment due to other n=2 | -35.12 (-100.0 to 29.8) |
The target mutation was defined as the hotspot mutation with the highest molecular frequency observed at screening excluding single nucleotide polymorphisms (SNPs, i.e., hotspot mutations observed at all timepoints with a minimum molecular frequency value of 30% and a variation coefficient greater than 0.15). The molecular frequency of target mutation at performed assessments during which the target mutation was not detected was assumed to be equal to 0%.
| percent change | Ribociclib+Letrozole (Core Phase) |
|---|---|
| Cycle 1, Day 15 n=12 | -42.45 (-100.0 to 77.5) |
| Cycle 2, Day 1 n=13 | -70.05 (-100.0 to 37.9) |
| First Imaging Evaluation n=11 | -56.76 (-100.0 to 1110.9) |
| End of Treatment due to PD n=12 | -24.31 (-100.0 to 707.2) |
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. Data row labels refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
| participants | Ribociclib+Letrozole (Core Phase) |
|---|---|
| None (Valid Liquid Biopsy Sample) n=105 | 59 |
| One (Valid Liquid Biopsy Sample) n=105 | 31 |
| Two (Valid Liquid Biopsy Sample) n=105 | 11 |
| Three or More (Valid Liquid Biopsy Sample) n=105 | 4 |
| None (Valid Tissue Sample) n=72 | 23 |
| One (Valid Tissue Sample) n=72 | 26 |
| Two (Valid Tissue Sample) n=72 | 17 |
| Three or More (Valid Tissue Sample) n=72 | 6 |
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. Data row labels refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
| participants | Ribociclib+Letrozole (Core Phase) |
|---|---|
| None (Valid Liquid Biopsy Sample) n=158 | 86 |
| One (Valid Liquid Biopsy Sample) n=158 | 39 |
| Two (Valid Liquid Biopsy Sample) n=158 | 21 |
| Three or More (Valid Liquid Biopsy Sample) n=158 | 12 |
| None (Valid Tissue Sample) n=67 | 15 |
| One (Valid Tissue Sample) n=67 | 25 |
| Two (Valid Tissue Sample) n=67 | 13 |
| Three or More (Valid Tissue Sample) n=67 | 14 |
Results data refer to the total number of evaluations (i.e. the number of participants in the biomarker analysis set with both valid baseline liquid biopsy and tissue sample multiplied by 39 considered genes).
| evaluations | Ribociclib+Letrozole (Core Phase) |
|---|---|
| Liquid Biopsy Hotspot-mutated, Tissue Sample Hotspot-mutated | 68 |
| Liquid Biopsy Hotspot-mutated, Tissue Sample Not Hotspot-mutated | 27 |
| Liquid Biopsy Not Hotspot-mutated, Tissue Sample Hotspot-mutated | 99 |
| Liquid Biopsy Not Hotspot-mutated, Tissue Sample Not Hotspot-mutated | 5227 |
Results data refer to the total number of evaluations (i.e. the number of participants in the biomarker analysis set with both valid baseline liquid biopsy and tissue sample multiplied by 39 considered genes).
| evaluations | Ribociclib+Letrozole (Core Phase) |
|---|---|
| Liquid Biopsy Hotspot-mutated, Tissue Sample Hotspot-mutated | 5 |
| Liquid Biopsy Hotspot-mutated, Tissue Sample Not Hotspot-mutated | 1 |
| Liquid Biopsy Not Hotspot-mutated, Tissue Sample Hotspot-mutated | 0 |
| Liquid Biopsy Not Hotspot-mutated, Tissue Sample Not Hotspot-mutated | 150 |
Time to progression (TTP) was defined as time from date of start of treatment to the date of event defined as the first documented progression or death due to underlying cancer.
| months | Ribociclib+Letrozole (Core Phase) | Alpelisib+Fulvestrant (Extension Phase) |
|---|---|---|
| Time to Progression (TTP) | 30.42 (21.42 to 40.41) | 10.25 (5.59 to 11.43) |
ORR was defined as the percentage of participants with a best overall response defined as complete response (CR) or partial response (PR): (CR+PR) per Response Evaluation Criteria in Solid Tumors (RECIST), v. 1.1. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
| percentage of participants | Ribociclib+Letrozole (Core Phase) | Alpelisib+Fulvestrant (Extension Phase) |
|---|---|---|
| Percentage of Participants With Best Overall Response Rate of Complete Response (CR) or Partial Response (PR) | 38.56 (32.32 to 45.09) | 17.65 (3.80 to 43.43) |
Clinical benefit rate (CBR) was defined as the percentage of participants with a best overall response of complete response (CR), or partial response (PR) or an overall lesion response of stable disease (SD), lasting as per local review, for a duration of at least 24 weeks. Per RECIST v. 1.1, CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter since the treatment started.
| percentage of participants | Ribociclib+Letrozole (Core Phase) | Alpelisib+Fulvestrant (Extension Phase) |
|---|---|---|
| Percentage of Participants With Clinical Benefit Rate | 73.31 (67.18 to 78.84) | 47.06 (22.98 to 72.19) |
No measurements were reported for this outcome.
No measurements were reported for this outcome.
Collected over Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 5.8 years in the core phase and 1.7 years in the extension phase.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Ribociclib+Letrozole (Core Phase) | 27/287 (9.4%) | 79/287 (27.5%) | 275/287 (95.8%) |
| Alpelisib+Fulvestrant (Extension Phase) | 3/21 (14.3%) | 6/21 (28.6%) | 20/21 (95.2%) |
| Event | Ribociclib+Letrozole (Core Phase) | Alpelisib+Fulvestrant (Extension Phase) |
|---|---|---|
| HyperglycaemiaMetabolism and nutrition disorders | 2/287 | 2/21 |
| HypertransaminasaemiaHepatobiliary disorders | 0/287 | 1/21 |
| JaundiceHepatobiliary disorders | 0/287 | 1/21 |
| Campylobacter infectionInfections and infestations | 0/287 | 1/21 |
| Urinary tract infectionInfections and infestations | 1/287 | 1/21 |
| HypokalaemiaMetabolism and nutrition disorders | 3/287 | 1/21 |
| Metastases to central nervous systemNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/287 | 1/21 |
| Pleural effusionRespiratory, thoracic and mediastinal disorders | 1/287 | 1/21 |
| RashSkin and subcutaneous tissue disorders | 0/287 | 1/21 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 7/287 | 0/21 |
| Event | Ribociclib+Letrozole (Core Phase) | Alpelisib+Fulvestrant (Extension Phase) |
|---|---|---|
| NeutropeniaBlood and lymphatic system disorders | 198/287 | 0/21 |
| HyperglycaemiaMetabolism and nutrition disorders | 11/287 | 14/21 |
| DiarrhoeaGastrointestinal disorders | 56/287 | 12/21 |
| AstheniaGeneral disorders | 89/287 | 8/21 |
| RashSkin and subcutaneous tissue disorders | 32/287 | 8/21 |
| AnaemiaBlood and lymphatic system disorders | 105/287 | 2/21 |
| NauseaGastrointestinal disorders | 95/287 | 7/21 |
| LeukopeniaBlood and lymphatic system disorders | 93/287 | 0/21 |
| Mucosal inflammationGeneral disorders | 16/287 | 5/21 |
| Weight decreasedInvestigations | 6/287 | 5/21 |
FAS
| Age, Continuous(years) | Ribociclib+Letrozole (Core Phase) |
|---|---|
| Mean | 65.5 ± 8.39 |
| Age, Customized(participants) | Ribociclib+Letrozole (Core Phase) |
|---|---|
| in utero | 0 |
| Preterm newborns infants | 0 |
| 0 - <28 days | 0 |
| 28 days - <2 years | 0 |
| 2 years - <12 years | 0 |
| 12 years - <18 years | 0 |
| 18 years - <65 years | 125 |
| 65 years - <85 years | 161 |
| >=85 years | 1 |
| Sex: Female, Male(Participants) | Ribociclib+Letrozole (Core Phase) |
|---|---|
| Female | 287 |
| Male | 0 |
| Race/Ethnicity, Customized(participants) | Ribociclib+Letrozole (Core Phase) |
|---|---|
| Caucasian | 280 |
| Asian | 1 |
| Unknown Race | 5 |
| Other Race | 1 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Undecided
Ran from Feb 2018 to primary completion in Dec 2023, 70 months.
Results were first posted in Jul 2026, 2 years 6 months after primary completion.
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Studies of the drugs tested here: Ribociclib · Letrozole · Alpelisib