CLEE011A2301

Novartis Pharma AG

Novartis Campus, Basel, Switzerland,

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, novartis.email@Novartis.com

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, novartis.email@Novartis.com

No

No

No

Final

16 Mar 2023

No

Yes

16 Mar 2023

No

The main objective of this trial was to compare progression-free survival between ribociclib in combination with letrozole to placebo plus letrozole among postmenopausal women with hormone receptor positive, HER2- negative, advanced breast cancer who received no prior therapy for advanced disease.

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.

17 Dec 2013

No

Yes

Argentina: 6

Australia: 16

Austria: 11

Belgium: 15

Brazil: 8

Canada: 16

Czechia: 19

Denmark: 12

Finland: 3

France: 43

Germany: 55

Hungary: 12

Ireland: 4

Israel: 32

Italy: 32

Korea, Republic of: 9

Lebanon: 15

Netherlands: 24

Norway: 9

Russian Federation: 11

Singapore: 9

South Africa: 2

Spain: 44

Sweden: 9

Taiwan: 19

Thailand: 4

United Kingdom: 4

United States: 213

Türkiye: 12

668

292

0

0

0

0

0

0

373

290

5

Overall study (overall period)

Randomised - controlled

Yes

Ribociclib

LEE011

Capsule, Tablet

Oral use

Ribociclib (600 mg, in three 200 mg hard gelatin capsules or tablets) was administered orally once daily on Days 1-21 of each 28-day cycle.

Letrozole

Tablet

Oral use

Letrozole (2.5 mg, tablets) was administered orally once daily on a continuous daily schedule (days 1-28 of each 28-day cycle)

Letrozole

Tablet

Oral use

Letrozole (2.5 mg, tablets) was administered orally once daily on a continuous daily schedule (days 1-28 of each 28-day cycle

Placebo

Tablet, Capsule

Oral use

Placebo (hard gelatin capsules or tablets) was administered orally once daily.

Ribociclib+ letrozole

Placebo + letrozole

Ribociclib+ letrozole

Placebo + letrozole

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 by investigator assessment according to RECIST 1.1. 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. 9999 indicates that the value was not estimable

Primary

Up to 23 months

Ribociclib+ letrozole v Placebo + letrozole

668

Pre-specified

0.556

2-sided

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 400 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.

Secondary

Up to approximately 87 months

Ribociclib+ letrozole v Placebo + letrozole

668

Pre-specified

0.765

2-sided

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 investigator 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.

Secondary

Up to 23 months

Ribociclib+ letrozole v Placebo + letrozole

668

Pre-specified

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 as per investigator 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.

Secondary

Up to 23 months

Ribociclib+ letrozole v Placebo + letrozole

668

Pre-specified

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. 9999 indicated that the value was not estimable.

Secondary

From baseline up to 23 months

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. 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. 9999 indicated that the value was not estimable.

Secondary

From baseline up to 23 months

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 assesed. 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. 9999 indicated that the value was not estimable.

Secondary

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 (post-treatment efficacy visits), assessed up to 23 months. Cycle = 28 days

Pre-treatment deaths were collected from day of participant’s informed consent to the day before first dose of study medication. On-treatment deaths were collected from start of treatment to 30 days after last dose of treatment or one day before first administration of crossover treatment (for crossover participants), whichever came first Crossover on-treatment deaths were collected from start of crossover treatment up to 30 days after last dose of crossover treatment. Post-treatment survival follow-up (FU) deaths were collected from day 31 after last dose of study treatment to end of study. Crossover post-treatment survival FU deaths were collected from day 31 after last dose of crossover treatment to end of study

Post-hoc

Pre-treatment: Up to 21 days before treatment. On-treatment: Up to 99 months. Crossover on-treatment: Up to 12 months after crossing-over.Post-treatment survival FU: Up to 99 months.Crossover post-treatment survival FU: Up to 12 months after crossing-over

On-treatment: From first dose to 30 days post-treatment (or start of crossover treatment), up to 99 Cross-over on-treatment: from first crossover dose to 30 days post-crossover treatment, up to 12 months.

Consistent with EudraCTdisclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.

25.1

Ribociclib + letrozole (on-treatment)

Crossover to ribociclib + letrozole (crossover on-treatment)

Placebo + letrozole (on-treatment)