Study of 2 Ribociclib Doses in Combination With Aromatase Inhibitors in Women With HR+, HER2- Advanced Breast Cancer

NCT03822468 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: CLEE011A22072018-004234-15
• Study Type: interventional
• Target: 376
• Locations: 22 countries
• Sites: 88

Brief Summary

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.

Conditions

Breast Cancer

Keywords

Breast Cancer (BC); hormone receptor (HR); HR-positive; human epidermal growth factor receptor 2 (HER2); HER2-negative; ER-positive; advanced breast cancer (aBC); ribociclib (LEE011); premenopausal; postmenopausal

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  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.

  Up to 23.8 months

Secondary Outcomes (8)

• Change From Baseline in QTc (With Fridericia's Correction) at Cycle 1 Day 15 (at 2 Hours Post-dose)

  Baseline and Cycle 1 Day 15 at 2 hours post-dose. Cycle = 28 days

• Progression-free Survival (PFS)

  Up to approximately 60 months

• Clinical Benefit Rate (CBR)

  Up to approximately 60 months

• Time to Response (TTR)

  Up to approximately 60 months

• Duration of Response (DOR)

  Up to approximately 60 months

Study Arms (2)

Ribociclib 400 mg

EXPERIMENTAL

Ribociclib 400 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+goserelin in premenopausal women)

Drug: Ribociclib; Drug: Anastrozole; Drug: Letrozole; Drug: Goserelin

Ribociclib 600 mg

ACTIVE COMPARATOR

Ribociclib 600 mg QD 3 weeks on/1 week off + letrozole or anastrozole (+ goserelin in premenopausal women)

Drug: Ribociclib; Drug: Anastrozole; Drug: Letrozole; Drug: Goserelin

Interventions

Ribociclib DRUG

Ribociclib (at a dosage of 400 mg or 600 mg) QD orally taken on days 1 to 21 of a 28-day cycle, followed by 7 days off ribociclib (days 22 to 28). Ribociclib was supplied as 200 mg tablets as individual patient supply packaged bottles.

Also known as: LEE011

Ribociclib 400 mg; Ribociclib 600 mg

Anastrozole DRUG

Anastrozole 1 mg tablets for oral use QD continuously

Ribociclib 400 mg; Ribociclib 600 mg

Letrozole DRUG

Letrozole 2.5 mg tablets for oral use QD continuously

Ribociclib 400 mg; Ribociclib 600 mg

Goserelin DRUG

Goserelin 3.6 mg subcutaneously once every 4 weeks (pre-menopausal women only)

Ribociclib 400 mg; Ribociclib 600 mg

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 ≥
• % 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (89)

Southern Cancer Center PC

Mobile, Alabama, 36608, United States

Location

Marin Cancer Care

Greenbrae, California, 94904, United States

Location

Rocky Mountain Cancer Centers

Longmont, Colorado, 80501, United States

Location

Florida Retina Institute

Orlando, Florida, 32804, United States

Location

Weinberg Cancer Institute at FSH

Baltimore, Maryland, 21237-3998, United States

Location

Nebraska Hematology Oncology P C

Lincoln, Nebraska, 68506, United States

Location

Nebraska Cancer Specialists

Omaha, Nebraska, 68154, United States

Location

Comprehensive Cancer Cntr Of Nevada

Henderson, Nevada, 89052, United States

Location

New York Oncology Hematology

Albany, New York, 12208, United States

Location

Mount Sinai School Of Medicine

New York, New York, 10029, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Millennium Research Clin Develop

Houston, Texas, 77090, United States

Location

Texas Oncology

McAllen, Texas, 78503, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

Novartis Investigative Site

San Juan, J5402DIL, Argentina

Location

Novartis Investigative Site

Innsbruck, Tyrol, 6020, Austria

Location

Novartis Investigative Site

Linz, 4010, Austria

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Novartis Investigative Site

Salzburg, 5020, Austria

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Novartis Investigative Site

Vienna, 1090, Austria

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Novartis Investigative Site

Edegem, 2650, Belgium

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Novartis Investigative Site

Namur, 5000, Belgium

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Novartis Investigative Site

Natal, Rio Grande do Norte, 59075 740, Brazil

Location

Novartis Investigative Site

Florianópolis, Santa Catarina, 88034 000, Brazil

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Novartis Investigative Site

São Paulo, São Paulo, 01317 000, Brazil

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Novartis Investigative Site

São Paulo, São Paulo, 04014-002, Brazil

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Novartis Investigative Site

Goiânia, 74605-070, Brazil

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Novartis Investigative Site

São José do Rio Preto, 15090 000, Brazil

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Novartis Investigative Site

Plovdiv, 4004, Bulgaria

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Novartis Investigative Site

Sofia, 1303, Bulgaria

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Novartis Investigative Site

Sofia, 1756, Bulgaria

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Novartis Investigative Site

Cambridge, Ontario, N1R 3G2, Canada

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Novartis Investigative Site

Valledupar, Cesar Department, 5602310, Colombia

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Novartis Investigative Site

Ibagué, Tolima Department, 730006, Colombia

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Novartis Investigative Site

Bogotá, 110131, Colombia

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Novartis Investigative Site

Bogotá, 110221, Colombia

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Novartis Investigative Site

Montería, 230002, Colombia

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Novartis Investigative Site

San José, 95008, Costa Rica

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Novartis Investigative Site

Brno, Czech Republic, 656 53, Czechia

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Novartis Investigative Site

Prague, 150 06, Czechia

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Novartis Investigative Site

Helsinki, 00029, Finland

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Novartis Investigative Site

Tampere, FIN-33521, Finland

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Novartis Investigative Site

Besançon, 25030, France

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Novartis Investigative Site

Caen, 14021, France

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Novartis Investigative Site

Clermont-Ferrand, 63011, France

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Novartis Investigative Site

Lyon 08, 69373, France

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Novartis Investigative Site

Marseille, 13273, France

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Novartis Investigative Site

Montpellier, 34298, France

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Novartis Investigative Site

Saint-Herblain, 44805, France

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Novartis Investigative Site

Strasbourg, F 67085, France

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Novartis Investigative Site

Valenciennes, 59300, France

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Novartis Investigative Site

Langen, Hesse, 63225, Germany

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Novartis Investigative Site

Augsburg, 86150, Germany

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Novartis Investigative Site

Berlin, 13581, Germany

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Novartis Investigative Site

Bonn, 53111, Germany

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Novartis Investigative Site

Dresden, 01127, Germany

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Novartis Investigative Site

Dresden, 01307, Germany

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Novartis Investigative Site

Essen, 45136, Germany

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Novartis Investigative Site

Tübingen, 72076, Germany

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Novartis Investigative Site

Weiden, 92637, Germany

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Novartis Investigative Site

Budapest, H 1122, Hungary

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Novartis Investigative Site

Debrecen, 4032, Hungary

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Novartis Investigative Site

Szolnok, H-5000, Hungary

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Novartis Investigative Site

Raipur, Chhattisgarh, 492001, India

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Novartis Investigative Site

Nagpur, Maharashtra, 441108, India

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Novartis Investigative Site

Bhubaneshwar, Odisha, 751007, India

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Novartis Investigative Site

Delhii, 110 085, India

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Novartis Investigative Site

Mumbai, 400 012, India

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Novartis Investigative Site

Amman, 11941, Jordan

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Novartis Investigative Site

Kaunas, LTU, LT 50161, Lithuania

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Novartis Investigative Site

Vilnius, LT-08660, Lithuania

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Novartis Investigative Site

Trujillo, La Libertad, 13011, Peru

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Novartis Investigative Site

San Borja, Lima region, 41, Peru

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Novartis Investigative Site

San Isidro, Lima region, 27, Peru

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Novartis Investigative Site

San Miguel, Lima region, 32, Peru

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Novartis Investigative Site

Lisbon, 1400-038, Portugal

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Novartis Investigative Site

Loures, 2674514, Portugal

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Novartis Investigative Site

Porto, 4200-072, Portugal

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Novartis Investigative Site

Arkhangelsk, 163045, Russia

Location

Novartis Investigative Site

Moscow, 111123, Russia

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Novartis Investigative Site

Moscow, 115478, Russia

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Novartis Investigative Site

Saint Petersburg, 197758, Russia

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Novartis Investigative Site

Cape Town, 7500, South Africa

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Novartis Investigative Site

Johannesburg, 2196, South Africa

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Novartis Investigative Site

Parktown, 2193, South Africa

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Novartis Investigative Site

Stockholm, 112 19, Sweden

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Novartis Investigative Site

Stockholm, SE-118 83, Sweden

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Novartis Investigative Site

Uppsala, 751 85, Sweden

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Novartis Investigative Site

Bangkok, 10700, Thailand

Location

Novartis Investigative Site

Chiang Mai, 50200, Thailand

Location

Related Publications (1)

• Cardoso F, Jacot W, Kuemmel S, Gupta S, Cruz F, Balaraman R, Ferreira A, Ahola T, Chapko Y, Zhukova L, Chiang W, Li Z, Ji Y, Kaakiou N, Bolotova N, Sparano JA. 600- vs 400-mg First-Line Ribociclib in Hormone Receptor-Positive/ERBB2-Negative Advanced Breast Cancer: The AMALEE Randomized Clinical Trial. JAMA Oncol. 2025 Nov 1;11(11):1356-1363. doi: 10.1001/jamaoncol.2025.3687.

  PMID: 40996770 DERIVED

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ribociclib; Anastrozole; Letrozole; Goserelin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Study director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2019
• First Posted: January 30, 2019
• Study Start: June 11, 2019
• Primary Completion: June 11, 2021
• Study Completion: August 30, 2024
• Last Updated: October 16, 2025
• Results First Posted: April 5, 2024

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

AR (1); CO (5); CA (1); FI (2); US (14); PE (4); PT (3); BU (3); LI (2); RU (4); SE (3); CZ (2); BE (2); FR (9); AU (4); TH (2); BR (6); HU (3); IN (5); ZA (3); DE (9); JO (1)