Primary outcomeNumber· Up to 23.8 months
Overall Response Rate (ORR)
| Group | Value (Percentage of participants) |
|---|---|
| Ribociclib 400 mg | 41.5 |
| Ribociclib 600 mg | 45.3 |
Trial · Interventional
CompletedPhase 2Results postedRegistry dataStudy of 2 Ribociclib Doses in Combination With Aromatase Inhibitors in Women With HR+, HER2- Advanced Breast Cancer
Short name AMALEE
NCTNCT03822468 (opens ClinicalTrials.gov in a new tab)Other idCLEE011A2207Other id2018-004234-15Other id2018
Overview
- Status
- Completed
- Phase
- Phase 2
- Enrollment
- 376 participants (actual)
- Sponsor
- Novartis Pharmaceuticals · Industry
- Design
- Randomized · Open label (no masking)
- Countries
23 countries
United States, Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, Colombia, Costa Rica, Czechia, Finland, France, Germany, Hungary, India, Jordan, Lithuania, Peru, Portugal, Russia, South Africa, Sweden, Thailand
- Start
- 11 Jun 2019
- Primary completion
- 11 Jun 2021
- Completion
- 30 Aug 2024
- First posted
- 30 Jan 2019
- Last update posted
- 16 Oct 2025
- Conditions
- Breast Cancer
Timeline
1 trial · 1 completed · 1 with posted results
- Completed
- Ongoing
- Not yet recruiting
- Stopped
- Estimated dates (est.)
- Results posted
2019202020212022202320242025
- Ph 2
Registry summary
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
The purpose of the study was to evaluate the safety and efficacy of a reduced ribociclib starting dose of 400 mg in combination with a non-steroidal aromatase inhibitor (NSAI) (letrozole or anastrozole) for the treatment of pre- and postmenopausal women with hormone receptor-positive (HR-positive), HER2-negative advanced breast cancer (aBC) who have received no prior therapy for advanced disease. Premenopausal women were required to receive goserelin in both treatment arms.
Interventions
- RibociclibDrug
- AnastrozoleDrug
- LetrozoleDrug
- GoserelinDrug
Arms2
Experimental
Ribociclib 400 mg
Ribociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women)
Active comparator
Ribociclib 600 mg
Ribociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women)
Primary outcomes1
Outcomes the sponsor listed as primary.
Overall Response Rate (ORR)
Time frame · Up to 23.8 months
Registry description
ORR defined as the percentage of participants with best overall response (BOR) of confirmed complete response (CR) or partial response (PR) assessed by local investigators according to RECIST 1.1. CR: Disappearance of all lesions with lymph nodes measuring \< 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.
Secondary outcomes(8)
Change From Baseline in QTc (With Fridericia's Correction) at Cycle 1 Day 15 (at 2 Hours Post-dose)
Time frame · Baseline and Cycle 1 Day 15 at 2 hours post-dose. Cycle = 28 days
Registry description
Electrocardiogram (ECG) data was collected via 12-lead digital ECG machines. Change from baseline in the QT interval (a segment of the ECG that reflects the time it takes for the heart to repolarize after each heartbeat) was corrected for heart rate using Fridericia's formula (ΔQTcF).
Progression-free Survival (PFS)
Time frame · Up to approximately 60 months
Registry description
Progression free survival (PFS) was defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause. PFS was censored if no PFS event was observed. The censoring date was the date of the last adequate tumor assessment. Clinical deterioration without objective radiological evidence was not considered as documented disease progression. PFS was assessed via a local radiology assessment as well as Blinded Independent Review Committee (BIRC) according to RECIST 1.1.
Clinical Benefit Rate (CBR)
Time frame · Up to approximately 60 months
Registry description
Clinical benefit rate (CBR) was defined as the proportion of patients with a best overall response of complete response (CR), or partial response (PR), or an overall response of stable disease (SD), lasting for at least 24 weeks. CR, PR, and SD were defined as per local review as well as Blinded Independent Review Committee (BIRC) according to RECIST 1.1. A patient was considered to have SD for 24 weeks or longer if a SD response was recorded at 24-1=23 weeks or later from randomization, allowing for the ±1 week visit window for tumor assessments. CR: Disappearance of all lesions with lymph nodes measuring \< 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. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
Time to Response (TTR)
Time frame · Up to approximately 60 months
Registry description
Time to response (TTR) was defined as the time from the date of randomization to the first documented response of either complete response (CR) or partial response (PR), which had to be subsequently confirmed (although the date of initial response was used, not the date of confirmation). CR and PR were based on tumor response data as per local review and according to RECIST 1.1. CR: Disappearance of all lesions with lymph nodes measuring \< 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.
Duration of Response (DOR)
Time frame · Up to approximately 60 months
Registry description
Duration of response (DOR) only applied to patients whose best overall response was complete response (CR) or partial response (PR) according to RECIST 1.1 based on tumor response data per local review. The start date was the date of first documented response of CR or PR (i.e. the start date of response, not the date when response was confirmed), and the end date was defined as the date of the first documented progression or death due to underlying cancer. Patients continuing without progression or death due to underlying cancer were censored at the date of their last adequate tumor assessment. CR: Disappearance of all lesions with lymph nodes measuring \< 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.
Pharmacokinetics (PK) of Ribociclib: Maximum Observed Plasma Concentration (Cmax)
Time frame · Cycle 1 Day 15 at pre-dose, and 2, 4, 6 and 24 hours post-dose. Cycle = 28 days
Registry description
PK parameters were calculated by non-compartmental analysis. Cmax is the maximum observed plasma drug concentration after single dose administration.
PK of Ribociclib: Time to Reach Observed Maximum Concentration (Tmax)
Time frame · Cycle 1 Day 15 at pre-dose, and 2, 4, 6 and 24 hours post-dose. Cycle = 28 days
Registry description
PK parameters were calculated by non-compartmental analysis. Tmax is the time to reach maximum observed plasma concentration. Actual recorded sampling times were considered for the calculations.
PK of Ribociclib: Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC0-24)
Time frame · Cycle 1 Day 15 at pre-dose, and 2, 4, 6 and 24 hours post-dose. Cycle = 28 days
Registry description
PK parameters were calculated by non-compartmental analysis. AUC0-24 is the area under the plasma concentration-time curve from 0 to 24 hours
Posted results
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
Primary outcome results
Secondary and other outcome results(7)
Secondary outcomeMean· Baseline and Cycle 1 Day 15 at 2 hours post-dose. Cycle = 28 days
Change From Baseline in QTc (With Fridericia's Correction) at Cycle 1 Day 15 (at 2 Hours Post-dose)
| Group | Value (milliseconds) | Spread |
|---|---|---|
| Ribociclib 400 mg | 12.5 | 12.91 |
| Ribociclib 600 mg | 19.7 | 18.50 |
Secondary outcomeMedian· Up to approximately 60 months
Progression-free Survival (PFS)
| Group | Value (Months) |
|---|---|
| Ribociclib 400 mg | 26.9 |
| Ribociclib 600 mg | 25.1 |
Secondary outcomeCount of participants· Up to approximately 60 months
Clinical Benefit Rate (CBR)
| Group | Value (Participants) |
|---|---|
| Ribociclib 400 mg | 142 |
| Ribociclib 600 mg | 133 |
Secondary outcomeMedian· Up to approximately 60 months
Time to Response (TTR)
| Group | Value (Months) |
|---|---|
| Ribociclib 400 mg | 13.1 |
| Ribociclib 600 mg | 9.0 |
Secondary outcomeMedian· Up to approximately 60 months
Duration of Response (DOR)
| Group | Value (Months) |
|---|---|
| Ribociclib 400 mg | 26.5 |
| Ribociclib 600 mg | 28.8 |
Secondary outcomeMean· Cycle 1 Day 15 at pre-dose, and 2, 4, 6 and 24 hours post-dose. Cycle = 28 days
Pharmacokinetics (PK) of Ribociclib: Maximum Observed Plasma Concentration (Cmax)
| Group | Value (nanogram / milliliter (ng / mL)) | Spread |
|---|---|---|
| Ribociclib 400 mg | 1240 | 739 |
| Ribociclib 600 mg | 1740 | 918 |
Secondary outcomeMedian· Cycle 1 Day 15 at pre-dose, and 2, 4, 6 and 24 hours post-dose. Cycle = 28 days
PK of Ribociclib: Time to Reach Observed Maximum Concentration (Tmax)
| Group | Value (hours (h)) |
|---|---|
| Ribociclib 400 mg | 2.08 |
| Ribociclib 600 mg | 4.00 |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| Ribociclib 400mgRibociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women) - Events up to 30 days safety follow-up | 5 / 188 | 38 / 188 | 175 / 188 |
| Ribociclib 600mgRibociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women) - Events up to 30 days safety follow-up | 6 / 188 | 37 / 188 | 178 / 188 |
| Ribociclib 400mg (Post-treatment Efficacy Follow-up)Ribociclib 400mg (Post-treatment efficacy follow-up) - Deaths in the post-treatment efficacy follow-up period were not considered adverse events. | 3 / 22 | 0 / 0 | 0 / 0 |
| Ribociclib 600 mg (Post-treatment Efficacy Follow-up)Ribociclib 600 mg (Post-treatment efficacy follow-up) - Deaths in the post-treatment efficacy follow-up period were not considered adverse events. | 2 / 26 | 0 / 0 | 0 / 0 |
Each cell reads participants affected / participants at risk, as the registry posted them.
Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works
Studies1
Studies that cite this trial.
More studies
1 study on this page
Indexing hint: Randomized controlled trial · 2025
600- vs 400-mg First-Line Ribociclib in Hormone Receptor-Positive/ERBB2-Negative Advanced Breast Cancer: The AMALEE Randomized Clinical Trial.
Cardoso et al. 2025JAMA oncologycited by 9
PMID 40996770PMC12464849DOI 10.1001/jamaoncol.2025.3687PUB-40996770
Free to read · publisher termsCC BY-NC-ND
Other registry references
References listed at the registry that are not in PepBank. They link to PubMed.
- DerivedJi Y, Wang C, Combes FP, Ho YY, Fasching PA, Untch M, Zarate JP, Crown J. Quantitative Pharmacology Justifying Ribociclib Dose in Early Breast Cancer. Clin Pharmacokinet. 2026 Aug;65(8):1217-1228. doi: 10.1007/s40262-026-01643-3. Epub 2026 Jun 23. PMID 42334791
Eligibility
Who could join, as posted.
- Sex
- Female
- Age
- from 18 Years up to 100 Years
- Healthy volunteers
- Not accepted
Inclusion and exclusion criteria, as posted
Key inclusion criteria:
* Patient has advanced (loco-regionally recurrent or metastatic) breast cancer not amenable to curative therapy.
* Patient has a histologically and/or cytologically confirmed diagnosis of ER-positive and/or PgR-positive breast cancer based on the most recently analyzed tissue sample, and all tested by local laboratory.
* Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing and based on the most recently analyzed tissue sample.
* Patient must have measurable disease, i.e., at least one measurable lesion according to RECIST version 1.1. (a lesion in a previously irradiated site may only be counted as a target lesion if there is clear evidence of progression since the irradiation).
* Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
* Standard 12-lead ECG values defined as the mean of the triplicate ECGs and assessed by the central laboratory:
* QTcF interval at screening \< 450 ms (QT interval using Fridericia's correction)
* Mean resting heart rate 50 to 90 bpm (determined from the ECG)
* Women of childbearing potential (CBP), defined as all women physiologically capable of becoming pregnant, must have confirmed negative serum pregnancy test (for β-hCG) within 14 days prior to randomization.
* Women of CBP must be willing to use highly effective methods of contraception.
Key Exclusion Criteria:
* Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's judgment.
* Patient who received any prior systemic anti-cancer therapy(including endocrine therapy, chemotherapy, prior CDK4/6 inhibitors) for aBC. Patients who received neo-/adjuvant therapy for breast cancer are eligible.
* Patient is concurrently using other anti-cancer therapy.
* Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major toxicities.
* Patient has received extended-field radiotherapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to randomization, and has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion). Patients in whom ≥
* 25% of the bone marrow has been previously irradiated are also excluded.
* Patient has a concurrent malignancy or malignancy within 3 years of the randomization date, with the exception of adequately treated basal or squamous cell skin carcinoma, or curatively resected cervical carcinoma in situ.
* Patients with central nervous system (CNS) involvement unless they meet specific stability criteria.
* Patient has clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality.
* Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study drug, and has not fully recovered from side effects of such treatment.
Other protocol-defined Inclusion/Exclusion may apply.
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