CLEE011A2404

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

09 Nov 2022

No

Yes

09 Nov 2022

No

The primary objective was to evaluate the safety and tolerability of ribociclib + letrozole in men and pre/postmenopausal women with HR+, HER2- aBC who received no prior hormonal 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.

30 Nov 2016

No

No

Argentina: 25

Austria: 30

Belgium: 228

Bulgaria: 52

Canada: 251

Chile: 7

Czechia: 65

Denmark: 10

Finland: 22

France: 306

Greece: 29

Hong Kong: 14

Hungary: 40

India: 103

Israel: 42

Italy: 554

Jordan: 20

Lebanon: 17

Malaysia: 28

Mexico: 17

Netherlands: 130

Norway: 8

Oman: 2

Panama: 4

Philippines: 14

Poland: 64

Portugal: 53

Russian Federation: 129

Saudi Arabia: 10

Singapore: 8

Slovakia: 14

Slovenia: 33

Spain: 526

Sweden: 14

Taiwan: 13

Thailand: 17

United Kingdom: 139

United States: 208

3246

2178

0

0

0

0

0

0

2173

1049

24

Core Phase

Not applicable

Ribociclib

LEE011

Tablet

Oral use

Ribociclib 200 mg tablets were centrally supplied to the investigators and administered orally once a day on days 1-21 of each 28-day cycle at a starting dose of 600 mg daily.

Letrozole

Tablet

Oral use

Letrozole was procured locally and administered orally once a day on a continuous daily schedule at a dose of 2.5 mg.

Goserelin

Implant

Subcutaneous use

Goserelin was procured locally and administered in men and premenopausal women as an injectable subcutaneous implant administered on day 1 starting at Cycle 1 and then every 28 days at a dose of 3.6 mg.

Leuprolide

Injection

Intramuscular use

Leuprolide was procured locally and administered in men and premenopausal women as an injectable intramuscular depot administered on day 1 starting at Cycle 1 and then every 28 days at a dose of 7.5 mg.

Extension Phase

Not applicable

Ribociclib

LEE011

Tablet, Tablet

Oral use

Ribociclib 200 mg tablets were centrally supplied to the investigators and administered orally once a day on days 1-21 of each 28-day cycle at a starting dose of 600 mg daily.

Leuprolide

Injection

Intramuscular use

Leuprolide was procured locally and administered in men and premenopausal women as an injectable intramuscular depot administered on day 1 starting at Cycle 1 and then every 28 days at a dose of 7.5 mg

Goserelin

Implant

Subcutaneous use

Goserelin was procured locally and administered in men and premenopausal women as an injectable subcutaneous implant administered on day 1 starting at Cycle 1 and then every 28 days at a dose of 3.6 mg.

Letrozole

Tablet

Oral use

Letrozole was procured locally and administered orally once a day on a continuous daily schedule at a dose of 2.5 mg.

Ribociclib + letrozole + goserelin/leuprolide

Ribociclib + letrozole + goserelin/leuprolide

Ribociclib + letrozole + goserelin/leuprolide

AEs were defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s). SAEs were defined as meeting at least 1 of the following criteria: is fatal or life-threatening, Results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, is medically significant, requires inpatient hospitalization or prolongation of existing hospitalization. A SAE which caused death of the participant was considered as fatal SAE. AEs were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1 to 5 were used to characterize the severity of the Adverse Event. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening and Grade 5: death related to AE. A participant with multiple severity grades for an AE is only counted under the maximum grade.

Primary

From start of treatment up to 30 days after last treatment (for participants who did not enter to the Extension phase) or up to last treatment in the Core phase (for participants who entered the Extension phase), assessed up to approximately 33 months.

Clinical benefit rate (CBR) is 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. CR, PR and SD are defined according to RECIST 1.1 based on investigator's 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. 95% CI was calculated using the exact binomial method.

Secondary

Up to approximately 33 months

Time to progression (TTP) is defined as time from date of start of treatment to the date of first documented progression or death due to underlying cancer. Participants with symptoms of rapidly progressing disease without radiologic evidence were classified as progression only when clear evidence of clinical deterioration was documented and/or patient discontinued due to ‘Disease progression’ or death due to study indication. When there was no documentation of radiologic evidence of progression, and the patient discontinued for ‘Disease progression’ due to documented clinical deterioration of disease, the date of discontinuation was used as date of progression. TTP was estimated using the Kaplan-Meier method. 95% CI of median was calculated according to Brookmeyer and Crowley method.

Secondary

Up to approximately 33 months

Overall response rate (ORR) is defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1 based on investigator's 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. 95% CI was calculated using the exact binomial method.

Secondary

Up to approximately 33 months

Change from baseline in FACT-B scores was assessed. FACT-B is a self-report instrument that measures multidimensional quality of life (QOL) in patients with breast cancer. The FACT-B consists of 37 questions that address physical, social, emotional, and functional well-being, with specific questions relevant to women with breast cancer. Each item has a score range of 0 (Not at all) to 4 (Very much), with a total score ranging from 0-148. The higher the score, the better the QOL reported by the participant. A positive change from baseline indicates improvement in QoL. Due to the nature of the questionnaire, only females were asked to complete this questionnaire.

Secondary

On Day 1 of Cycle 1, 2, 3, 4 ,5, 6, 8, 10, 12 and after that every 3 cycles, and End of treatment, assessed up to 33 months. Cycle=28 days

AEs were defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s). SAEs were defined as meeting at least 1 of the following criteria: is fatal or life-threatening, Results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, is medically significant, requires inpatient hospitalization or prolongation of existing hospitalization. AEs were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1 to 5 were used to characterize the severity of the Adverse Event. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening and Grade 5: death related to AE. A participant with multiple severity grades for an AE is only counted under the maximum grade.

Secondary

From first dose of treatment in the Extension phase up to 30 days after last dose of treatment, assessed up approximately 37.6 months

Clinical benefit as assessed by the Investigator during Extension phase

Secondary

On Day 1 of every 3 cycles, starting from Cycle 1 of the Extension phase until end of treatment, assessed up to 37.4 months. Cycle= 28 days

Core: First dose to 30 days after last treatment (non-Extension participants) or last treatment in the Core (Extension participants), assessed up to 33 months. Extension: First dose to 30 days after last treatment, assessed up to approx. 37.6 months.

Consistent with EudraCT disclosure 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

All patients- Extension phase

All patients- Core phase