Study of Efficacy and Safety in Premenopausal Women With Hormone Receptor Positive, HER2-negative Advanced Breast Cancer (MONALEESA-7)

A Phase III Randomized, Double-blind, Placebo-controlled Study of LEE011 or Placebo in Combination With Tamoxifen and Goserelin or a Non-steroidal Aromatase Inhibitor (NSAI) and Goserelin for the Treatment of Premenopausal Women With Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer

The purpose of this study was to determine whether treatment with tamoxifen or a non-steroidal aromatase inhibitors (NSAI) + goserelin + LEE011 prolonged progression-free survival (PFS) compared to treatment with tamoxifen or a NSAI + goserelin + placebo in premenopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer.

Study Overview

• Status: Completed
• Conditions: Advanced Metastatic Breast Cancer
• Intervention / Treatment: Drug: Ribociclib; Drug: Tamoxifen; Drug: Letrozole; Drug: Anastrozole; Drug: Goserelin; Drug: Placebo

Detailed Description

This was a randomized, Phase III, double-blind, global study comparing the treatment efficacy and safety of ribociclib + goserelin + tamoxifen or a NSAI (letrozole or anastrozole) versus placebo + goserelin + tamoxifen or a NSAI in premenopausal women with HR+, HER2- advanced breast cancer.

Eligible participants were randomized in a 1:1 ratio to either the ribociclib arm or the placebo arm. Study treatment continued until disease progression, unacceptable toxicity, death, or discontinuation for any other reason.

Participants who discontinued treatment due to reasons other than disease progression or withdrawal of consent for efficacy follow-up continued to be monitored until disease progression, death, withdrawal of consent, loss to follow-up, or subject/guardian decision (post-treatment efficacy follow-up).

All participants who discontinued treatment were followed for survival until the predetermined number of overall survival (OS) events was reached.

Following the final OS analysis (performed when approximately 189 deaths were recorded) and with protocol amendment 6 (dated 18-Jul-2019), participants and investigators were unblinded and those participants in the placebo arm had the opportunity to cross-over to the ribociclib arm to receive ribociclib + goserelin + NSAI. Cross-over was optional and was conducted at the investigator's discretion and upon participant consent.

• Study Type: Interventional
• Enrollment (Actual): 672
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Cordoba, Argentina, X5004FHP
    • Novartis Investigative Site
  • Jujuy, Argentina, 4600
    • Novartis Investigative Site
  • La Rioja, Argentina, 5300
    • Novartis Investigative Site
• Australia
  • New South Wales
    • Waratah, New South Wales, Australia, 2298
      • Novartis Investigative Site
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Novartis Investigative Site
    • Heidelberg, Victoria, Australia, 3084
      • Novartis Investigative Site
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Novartis Investigative Site
    • Nedlands, Western Australia, Australia, 6009
      • Novartis Investigative Site
• Belgium
  • Bruxelles, Belgium, 1000
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
  • Namur, Belgium, 5000
    • Novartis Investigative Site
  • Wilrijk, Belgium, 2610
    • Novartis Investigative Site
• Brazil
  • PR
    • Londrina, PR, Brazil, 86015-520
      • Novartis Investigative Site
  • RS
    • Ijuí, RS, Brazil, 98700-000
      • Novartis Investigative Site
    • Passo Fundo, RS, Brazil, 99010-260
      • Novartis Investigative Site
  • SP
    • Barretos, SP, Brazil, 14784 400
      • Novartis Investigative Site
    • Sao Paulo, SP, Brazil, 01317-002
      • Novartis Investigative Site
    • Sao Paulo, SP, Brazil, 04014-002
      • Novartis Investigative Site
    • São Paulo, SP, Brazil, 01509-900
      • Novartis Investigative Site
• Bulgaria
  • Sofia, Bulgaria, 1303
    • Novartis Investigative Site
  • Varna, Bulgaria, 9010
    • Novartis Investigative Site
• Canada
  • Quebec, Canada, G1S 4L8
    • Novartis Investigative Site
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Novartis Investigative Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Novartis Investigative Site
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Novartis Investigative Site
  • Quebec
    • Montréal, Quebec, Canada, H3G 1L5
      • Novartis Investigative Site
• Colombia
  • Bogota, Colombia, 110221
    • Novartis Investigative Site
  • Monteria, Colombia, 230004
    • Novartis Investigative Site
• France
  • Caen, France, 14021
    • Novartis Investigative Site
  • Lille Cedex, France, 59020
    • Novartis Investigative Site
  • Lyon, France, 69373
    • Novartis Investigative Site
  • Montpellier, France, 34298
    • Novartis Investigative Site
  • Paris, France, 75015
    • Novartis Investigative Site
  • Rouen, France, 76038
    • Novartis Investigative Site
  • Strasbourg, France, 67000
    • Novartis Investigative Site
  • Toulouse, France, 31059
    • Novartis Investigative Site
• Germany
  • Bonn, Germany, 53111
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Erlangen, Germany, 91054
    • Novartis Investigative Site
  • Essen, Germany, 45136
    • Novartis Investigative Site
  • Esslingen, Germany, 73730
    • Novartis Investigative Site
  • Kiel, Germany, 24105
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • Muehlhausen, Germany, 99974
    • Novartis Investigative Site
  • Muenchen, Germany, 81377
    • Novartis Investigative Site
  • Offenbach, Germany, 63069
    • Novartis Investigative Site
  • Ravensburg, Germany, 88214
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
• Greece
  • Heraklion Crete, Greece, 711 10
    • Novartis Investigative Site
  • GR
    • Thessaloniki, GR, Greece, 54645
      • Novartis Investigative Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Novartis Investigative Site
  • Kowloon, Hong Kong
    • Novartis Investigative Site
  • Wan Chai, Hong Kong
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, H 1122
    • Novartis Investigative Site
  • Budapest, Hungary, 1134
    • Novartis Investigative Site
  • Budapest, Hungary, H-1032
    • Novartis Investigative Site
  • Debrecen, Hungary, 4032
    • Novartis Investigative Site
  • Szeged, Hungary, 6720
    • Novartis Investigative Site
  • Szolnok, Hungary, H-5000
    • Novartis Investigative Site
• India
  • Mumbai, India, 400 012
    • Novartis Investigative Site
  • Karnataka
    • Bangalore, Karnataka, India, 560 095
      • Novartis Investigative Site
  • Maharashtra
    • Nashik, Maharashtra, India, 422 004
      • Novartis Investigative Site
  • West Bengal
    • Kolkatta, West Bengal, India, 700 053
      • Novartis Investigative Site
• Italy
  • Napoli, Italy, 80131
    • Novartis Investigative Site
  • AQ
    • L Aquila, AQ, Italy, 67100
      • Novartis Investigative Site
  • BN
    • Benevento, BN, Italy, 82100
      • Novartis Investigative Site
  • BO
    • Bologna, BO, Italy, 40138
      • Novartis Investigative Site
  • CR
    • Cremona, CR, Italy, 26100
      • Novartis Investigative Site
  • CT
    • Catania, CT, Italy, 95124
      • Novartis Investigative Site
  • FC
    • Meldola, FC, Italy, 47014
      • Novartis Investigative Site
  • FE
    • Cona, FE, Italy, 44100
      • Novartis Investigative Site
  • GE
    • Genova, GE, Italy, 16132
      • Novartis Investigative Site
  • LE
    • Lecce, LE, Italy, 73100
      • Novartis Investigative Site
  • LU
    • Lucca, LU, Italy, 55100
      • Novartis Investigative Site
  • MC
    • Macerata, MC, Italy, 62100
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20141
      • Novartis Investigative Site
  • PG
    • Perugia, PG, Italy, 06129
      • Novartis Investigative Site
  • PO
    • Prato, PO, Italy, 59100
      • Novartis Investigative Site
  • PV
    • Pavia, PV, Italy, 27100
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00168
      • Novartis Investigative Site
  • TO
    • Candiolo, TO, Italy, 10060
      • Novartis Investigative Site
  • TR
    • Terni, TR, Italy, 05100
      • Novartis Investigative Site
  • UD
    • Udine, UD, Italy, 33100
      • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 06351
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 03722
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 05505
    • Novartis Investigative Site
  • Gyeonggi Do
    • Bundang Gu, Gyeonggi Do, Korea, Republic of, 13620
      • Novartis Investigative Site
  • Korea
    • Gyeonggi do, Korea, Korea, Republic of, 10408
      • Novartis Investigative Site
• Lebanon
  • Ashrafieh, Lebanon, 166830
    • Novartis Investigative Site
  • Beirut, Lebanon, 1107 2020
    • Novartis Investigative Site
  • Beirut, Lebanon, 166378
    • Novartis Investigative Site
  • Beirut, Lebanon, 10999
    • Novartis Investigative Site
  • Saida, Lebanon, 652
    • Novartis Investigative Site
  • LBN
    • El Chouf, LBN, Lebanon, 1503201002
      • Novartis Investigative Site
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Novartis Investigative Site
  • Johor
    • Johor Bahru, Johor, Malaysia, 81100
      • Novartis Investigative Site
• Mexico
  • Edo. De México
    • Metepec, Edo. De México, Mexico, 01722
      • Novartis Investigative Site
  • Guanajuato
    • Leon, Guanajuato, Mexico, 37000
      • Novartis Investigative Site
  • Monterrey
    • Monterrey Nuevo Leon, Monterrey, Mexico, 64710
      • Novartis Investigative Site
• Poland
  • Gdansk, Poland, 80 952
    • Novartis Investigative Site
  • Konin, Poland, 62 500
    • Novartis Investigative Site
• Portugal
  • Lisboa, Portugal, 1500 650
    • Novartis Investigative Site
  • Lisboa, Portugal, 1400-038
    • Novartis Investigative Site
  • Lisboa, Portugal, 1099 023
    • Novartis Investigative Site
  • Porto, Portugal, 4200-072
    • Novartis Investigative Site
  • Porto, Portugal, 4200 319
    • Novartis Investigative Site
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 192148
    • Novartis Investigative Site
• Saudi Arabia
  • Riyadh, Saudi Arabia, 11426
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119228
    • Novartis Investigative Site
  • Singapore, Singapore, 168583
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28034
    • Novartis Investigative Site
  • Madrid, Spain, 28033
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Alicante
    • Elche, Alicante, Spain, 03203
      • Novartis Investigative Site
  • Andalucia
    • Almeria, Andalucia, Spain, 04009
      • Novartis Investigative Site
    • Malaga, Andalucia, Spain, 29010
      • Novartis Investigative Site
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Novartis Investigative Site
    • Sant Joan Despi, Barcelona, Spain, 08970
      • Novartis Investigative Site
  • Catalunya
    • Badalona, Catalunya, Spain, 08916
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08003
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46010
      • Novartis Investigative Site
  • Galicia
    • Santiago De Compostela, Galicia, Spain, 15706
      • Novartis Investigative Site
  • Islas Baleares
    • Mallorca, Islas Baleares, Spain, 07198
      • Novartis Investigative Site
  • Madrid
    • Alcorcon, Madrid, Spain, 28922
      • Novartis Investigative Site
  • Pais Vasco
    • San Sebastian, Pais Vasco, Spain, 20080
      • Novartis Investigative Site
  • Vizcaya
    • Baracaldo, Vizcaya, Spain, 48903
      • Novartis Investigative Site
• Switzerland
  • Geneve, Switzerland, 1205
    • Novartis Investigative Site
• Taiwan
  • Changhua, Taiwan, 50006
    • Novartis Investigative Site
  • Kaohsiung, Taiwan, 83301
    • Novartis Investigative Site
  • New Taipei City, Taiwan, 23561
    • Novartis Investigative Site
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Taipei, Taiwan, 11217
    • Novartis Investigative Site
  • Taipei, Taiwan, 10449
    • Novartis Investigative Site
  • Taipei, Taiwan, 103616
    • Novartis Investigative Site
  • Taoyuan, Taiwan, 33305
    • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10330
    • Novartis Investigative Site
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
• Turkey
  • Adana, Turkey, 01160
    • Novartis Investigative Site
  • Ankara, Turkey, 06100
    • Novartis Investigative Site
  • Diyarbakir, Turkey, 21000
    • Novartis Investigative Site
  • Edirne, Turkey, 22030
    • Novartis Investigative Site
  • Izmir, Turkey, 35040
    • Novartis Investigative Site
  • TUR
    • Istanbul, TUR, Turkey, 34098
      • Novartis Investigative Site
• United Arab Emirates
  • Al Ain Abu Dhabi, United Arab Emirates
    • Novartis Investigative Site
• United States
  • California
    • Bakersfield, California, United States, 93309
      • Comprehensive Blood and Cancer SC-2
    • Los Angeles, California, United States, 90095
      • University Of California Los Angeles Dept of Onc
  • Colorado
    • Denver, Colorado, United States, 80218
      • Comprehensive Cancer Center at Saint Joseph Hospital SC
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Danbury Hospital SC
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists Onc Dept
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists SC-2
    • Hollywood, Florida, United States, 33021
      • Memorial Cancer Institute SC
    • Miami, Florida, United States, 33136
      • University Of Miami Univ Miami 2
  • Georgia
    • Marietta, Georgia, United States, 30060
      • NorthWest Georgia Oncology Centers IRB
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Moanalua Medical Center. Attn: Oncology Dept SC
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago SC-3
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute SC
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel CCC At JH Dept of Onc.
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Onc Dept
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center Onc Dept
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington Uni School of Med SC
  • New Jersey
    • Neptune, New Jersey, United States, 07754
      • Meridian Health Systems SC
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Hospital SC-2
  • New York
    • Lake Success, New York, United States, 11042
      • Clinical Research Alliance .
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Univ Medical Center Duke (SC)
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State University Milton S Hershey Medical Center
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Bon Secours Cancer Center SC
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Erlanger Medical Center SC
    • Nashville, Tennessee, United States, 37203
      • SCRI Oncology Partners Tennessee Oncology (3)
  • Texas
    • Fort Worth, Texas, United States, 76104
      • The Center for Cancer and Blood Disorders SC
    • Houston, Texas, United States, 77030
      • Uni of TX MD Anderson Cancer Cntr SC-5
    • Houston, Texas, United States, 77030
      • Methodist Hospita Methodist Can Cen Dept of Oncology
    • San Antonio, Texas, United States, 78234
      • Brooke Army Medical Center SC
    • San Antonio, Texas, United States, 78229
      • Mays Cancer Ctr Uthsa Mdacc SC-4
  • Utah
    • Ogden, Utah, United States, 84403-3105
      • Northern Utah Cancer Associates
  • Virginia
    • Midlothian, Virginia, United States, 23114
      • Bon Secours Virginia Health System
  • Washington
    • Everett, Washington, United States, 98201
      • Providence Regional Cancer Partnership
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Onco Kadlec Clinic Hematology & Onc
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties Dept of Onc
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-6164
      • University of Wisconsin / Paul P. Carbone Comp Cancer Center Univ Wisc 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 59 years (Adult)
• Accepts Healthy Volunteers: No

Description

Key inclusion criteria:

• Patients had advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy
• Patients were premenopausal or perimenopausal at the time of study entry
• Patients who had received (neo) adjuvant therapy for breast cancer were eligible
• Patients had a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer
• Patients had HER2-negative breast cancer
• Patients must have either had measurable disease or If no measurable disease was present, then at least one predominantly lytic bone lesion
• Patients had an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Patients had adequate bone marrow and organ function

Key exclusion criteria:

• Patients who had received a prior CDK4/6 inhibitor
• Patients were postmenopausal
• Patients who currently had inflammatory breast cancer at screening.
• Patients who had received any prior hormonal anti-cancer therapy for advanced breast cancer, except for ≤ 14 days of tamoxifen or NSAI ± goserelin for advanced breast cancer prior to randomization.
• Patients had a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated basal cell skin carcinoma, squamous cell skin carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
• Patients with CNS metastases.
• Patients had active cardiac disease or a history of cardiac dysfunction
• Patients were currently using other antineoplastic agents
• Patients were pregnant or nursing or physiologically capable of becoming pregnant and not using highly effective contraception.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ribociclib + NSAI/tamoxifen + goserelin; Ribociclib 600 mg daily oral (3 weeks on/ 1 week off) in combination with NSAI or tamoxifen (tamoxifen 20 mg daily oral or letrozole 2.5 mg daily oral or anastrozole 1 mg daily oral) and goserelin 3.6 mg subcutaneous injection (once every 28 days)	Drug: Ribociclib; Ribociclib (600 mg, in three 200 mg hard gelatin capsules) was administered orally once daily on Days 1-21 of each 28-day cycle.; Other Names: LEE011; Drug: Tamoxifen; Tamoxifen (20 mg, tablets) was administered orally on a continuous daily schedule (days 1-28 of each 28-day cycle); Drug: Letrozole; Letrozole (2.5 mg, tablets) was administered orally once daily on a continuous daily schedule (days 1-28 of each 28-day cycle); Drug: Anastrozole; Anastrozole (1 mg, tablets) was administered orally once daily on a continuous daily schedule (days 1-28 of each 28-day cycle); Drug: Goserelin; Goserelin (3.6 mg, subcutaneous implant) was administered on day 1 of every 28-day cycle
Placebo Comparator: Placebo + NSAI/tamoxifen + goserelin; Placebo daily oral (3 weeks on/ 1 week off) in combination with NSAI or tamoxifen (tamoxifen 20 mg daily oral or letrozole 2.5 mg daily oral or anastrozole 1 mg daily oral) and goserelin 3.6 mg subcutaneous injection (once every 28 days). Participants were unblinded once the final OS analysis was conducted and after the implementation of protocol amendment 6 (16-Jul-2019) and were given the option to crossover to treatment with ribociclib +NSAI/tamoxifen + goserelin.	Drug: Tamoxifen; Tamoxifen (20 mg, tablets) was administered orally on a continuous daily schedule (days 1-28 of each 28-day cycle); Drug: Letrozole; Letrozole (2.5 mg, tablets) was administered orally once daily on a continuous daily schedule (days 1-28 of each 28-day cycle); Drug: Anastrozole; Anastrozole (1 mg, tablets) was administered orally once daily on a continuous daily schedule (days 1-28 of each 28-day cycle); Drug: Goserelin; Goserelin (3.6 mg, subcutaneous implant) was administered on day 1 of every 28-day cycle; Drug: Placebo; Placebo (hard gelatin capsules) was administered orally once daily on Days 1-21 of each 28-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) by Investigator Assessment	PFS was defined as the period starting from the date of randomization to the date of the first documented progression or death caused by any reason. In cases where patients did not experience an event, the PFS was censored at 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 local radiology assessment according to RECIST 1.1. As per protocol, the final PFS analysis was conducted after approximately 392 PFS events were documented. The Kaplan-Meier method was used to estimate PFS, and the median PFS, along with 95% confidence intervals, was reported for each treatment group. A stratified Cox regression model was used to estimate the hazard ratio of PFS, along with 95% confidence interval	From randomization to first documented progression or death, assessed up to approximately 29 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS was defined as the time from the date of randomization to the date of death from any cause. In cases where the patient's death was not recorded, the OS value was censored at the date of the last known patient's survival status. OS was estimated using the Kaplan-Meier method. As per protocol, the final OS analysis was conducted after approximately 189 deaths were documented. The median OS, along with 95% confidence intervals, was reported for each treatment group.The distribution of OS between the two treatment arms was compared using a log-rank test at one-sided cumulative 2.5% level of significance. A stratified Cox regression was used to estimate the OS hazard ratio and the associated 95% CI.	From randomization to death, assessed up to approximately 45 months
Overall Response Rate (ORR) by Investigator Assessment	ORR is the percentage of participants with the best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1 as per local assessment. 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.	Up to approximately 29 months
Clinical Benefit Rate (CBR) by Investigator Assessment	Percentage of participants with complete response (CR) or partial response (PR) or stable disease (SD) lasting 24 weeks or longer as defined in RECIST 1.1 and local assessment. 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; SD = Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease: PD = At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20% the sum must also demonstrate an absolute increase of at least 5 mm.	Up to approximately 29 months
Time to Response (TTR) by Investigator Assessment	Time to response is the time from the date of randomization to the first documented response (CR or PR, which must be confirmed subsequently) according to RECIST 1.1 as per local assessment. The Kaplan-Meier method was used to estimate TTR, and the median TTR, along with 95% confidence intervals, was reported for each treatment group. Participants who did not achieve a confirmed response were censored at the maximum follow-up time for patients who had a PFS event (i.e. either progressed or died due to any cause) or at the date of last adequate tumor assessment otherwise. 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.	Up to approximately 29 months
Duration of Response (DOR) by Investigator Assessment	DOR was defined as the time from the first documented response (CR or PR) to the first documented progression or death due to underlying cancer as defined in RECIST 1.1 per investigator assessment. The Kaplan-Meier method was used to estimate DOR, and the median DOR, along with 95% confidence intervals, was reported for each treatment group. If a participant had not had an event, duration was censored at the date of last adequate tumor assessment. 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.	Up to approximately 29 months
Time to Definitive Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) by at Least One Category of the Score	ECOG PS categorized patients based on their ability to perform daily activities and self-care, with scores ranging from 0 to 5. A score of 0 indicated no restrictions in activity, while higher scores indicated increasing limitations. Time to definitive deterioration was defined as the time from the date of randomization to the date of the event, defined as experiencing an increase in ECOG PS by at least one category from the baseline or death. A deterioration was considered definitive if no improvements in the ECOG PS were observed at a subsequent time. The Kaplan-Meier method was used to estimate the distribution, and the median time to definitive deterioration, along with 95% confidence intervals, was reported for each treatment group. Patients receiving any further therapy prior to definitive worsening were censored at their date of last assessment prior to start of therapy. Patients that had not worsened at the data cutoff point were censored at the date of last assessment.	Baseline, up to approximately 29 months
Time to Definitive 10% Deterioration in the Global Health Status/Quality of Life (GHS/QoL) Scale Score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30)	The EORTC QLQ-C30 is a questionnaire that includes 5 functional scales, 3 symptom scales, 1 GHS/QoL scale, and 6 single items. GHS/QoL scale score ranges between 0 and 100. A high score for GHS/QoL represents better functioning or QoL.The time to definitive 10% deterioration is defined as the time from the date of randomization to the date of event, which is defined as at least 10% relative to baseline worsening of the QoL score (without further improvement above the threshold) or death due to any cause. The Kaplan-Meier method was used to estimate the distribution, and the median time to definitive 10% deterioration, along with 95% confidence intervals, was reported for each treatment group. If a patient had not had an event, time to deterioration was censored at the date of the last adequate QoL evaluation.	Up to approximately 29 months
Change From Baseline in the GHS/QoL Scale Score of the EORTC QLQ-C30	The EORTC QLQ-C30 is a questionnaire that includes 5 functional scales, 3 symptom scales, 1 GHS/QoL scale, and 6 single items. GHS/QoL scale score ranges between 0 and 100. A high score for GHS/QoL represents better functioning or QoL.The change from baseline in the GHS/QoL score was assessed. A positive change from baseline indicated improvement. For subjects who discontinued treatment without disease progression, post-treatment efficacy visits occurred every 8 weeks during the initial 18 months since start of treatment, followed by visits every 12 weeks until disease progression.	Baseline, every 2 cycles after randomization during 18 months, then every 3 cycles up to end of treatment (EOT); EOT; and every 8 or 12 weeks post-treatment until progression, assessed up to approximately 29 months. Cycle=28 days

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Lu YS, Im SA, Colleoni M, Franke F, Bardia A, Cardoso F, Harbeck N, Hurvitz S, Chow L, Sohn J, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Babu KG, Wheatley-Price P, De Laurentiis M, Im YH, Kuemmel S, El-Saghir N, O'Regan R, Gasch C, Solovieff N, Wang C, Wang Y, Chakravartty A, Ji Y, Tripathy D. Updated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR+/HER2- Advanced Breast Cancer in MONALEESA-7: A Phase III Randomized Clinical Trial. Clin Cancer Res. 2022 Mar 1;28(5):851-859. doi: 10.1158/1078-0432.CCR-21-3032.
• Burris HA, Chan A, Bardia A, Thaddeus Beck J, Sohn J, Neven P, Tripathy D, Im SA, Chia S, Esteva FJ, Hart L, Zarate JP, Ridolfi A, Lorenc KR, Yardley DA. Safety and impact of dose reductions on efficacy in the randomised MONALEESA-2, -3 and -7 trials in hormone receptor-positive, HER2-negative advanced breast cancer. Br J Cancer. 2021 Aug;125(5):679-686. doi: 10.1038/s41416-021-01415-9. Epub 2021 Jun 22.
• Yardley DA. MONALEESA clinical program: a review of ribociclib use in different clinical settings. Future Oncol. 2019 Aug;15(23):2673-2686. doi: 10.2217/fon-2019-0130. Epub 2019 Jul 15.
• Im SA, Lu YS, Bardia A, Harbeck N, Colleoni M, Franke F, Chow L, Sohn J, Lee KS, Campos-Gomez S, Villanueva-Vazquez R, Jung KH, Chakravartty A, Hughes G, Gounaris I, Rodriguez-Lorenc K, Taran T, Hurvitz S, Tripathy D. Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer. N Engl J Med. 2019 Jul 25;381(4):307-316. doi: 10.1056/NEJMoa1903765. Epub 2019 Jun 4.
• Tripathy D, Im SA, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz SA, Chow L, Sohn J, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Babu KG, Wheatley-Price P, De Laurentiis M, Im YH, Kuemmel S, El-Saghir N, Liu MC, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu YS. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018 Jul;19(7):904-915. doi: 10.1016/S1470-2045(18)30292-4. Epub 2018 May 24.
• Bardia A, Su F, Solovieff N, Im SA, Sohn J, Lee KS, Campos-Gomez S, Jung KH, Colleoni M, Vazquez RV, Franke F, Hurvitz S, Harbeck N, Chow L, Taran T, Rodriguez Lorenc K, Babbar N, Tripathy D, Lu YS. Genomic Profiling of Premenopausal HR+ and HER2- Metastatic Breast Cancer by Circulating Tumor DNA and Association of Genetic Alterations With Therapeutic Response to Endocrine Therapy and Ribociclib. JCO Precis Oncol. 2021 Sep 1;5:PO.20.00445. doi: 10.1200/PO.20.00445. eCollection 2021. Erratum In: JCO Precis Oncol. 2023 Mar;7:e2300102.
• Prat A, Chaudhury A, Solovieff N, Pare L, Martinez D, Chic N, Martinez-Saez O, Braso-Maristany F, Lteif A, Taran T, Babbar N, Su F. Correlative Biomarker Analysis of Intrinsic Subtypes and Efficacy Across the MONALEESA Phase III Studies. J Clin Oncol. 2021 May 1;39(13):1458-1467. doi: 10.1200/JCO.20.02977. Epub 2021 Mar 26. Erratum In: J Clin Oncol. 2021 Nov 1;39(31):3525. J Clin Oncol. 2023 Apr 20;41(12):2299-2301.

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2014
• Primary Completion (Actual): August 21, 2017
• Study Completion (Actual): April 20, 2023

Study Registration Dates

• First Submitted: October 22, 2014
• First Submitted That Met QC Criteria: October 28, 2014
• First Posted (Estimated): October 29, 2014

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: February 13, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Tamoxifen; Phase III; LEE011; ribociclib; Premenopausal; Letrozole; CDK4/6; HER2-negative; Advanced breast cancer; Goserelin; CDK4; CDK6; Anastrozole; CDK; ER-positive; PR-positive; HR-positive
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Letrozole; Goserelin; Tamoxifen; Anastrozole
• Other Study ID Numbers: CLEE011E2301; 2014-001931-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No