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Trial · Interventional

CompletedPhase 2Results postedRegistry data

Efficacy and Safety of Ribociclib in Pre- and Postmenopausal Chinese Women With HR Positive, HER2-negative, Advanced Breast Cancer.

Overview

Status
Completed
Phase
Phase 2
Enrollment
327 participants (actual)
Sponsor
Novartis Pharmaceuticals · Industry
Design
Randomized · Quadruple masking
Countries
1 country

China

Start
29 Aug 2018
Primary completion
25 Apr 2022
Completion
9 May 2025
First posted
14 Sept 2018
Last update posted
8 Jul 2026
Conditions
Breast Cancer

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20182020202220242026
  1. Ph 2

    Efficacy and Safety of Ribociclib in Pre- and Postmenopausal Chinese Women With HR Positive, HER2-negative, Advanced Breast Cancer.

    NCT03671330

    29 Aug 2018 to 9 May 2025

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

This was a randomized, double-blind, placebo-controlled study conducted in Chinese women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer, plus an open-label, single-arm pharmacokinetic (PK) subset in postmenopausal Chinese women with HR+, HER2- advanced breast cancer.

Interventions

  • Ribociclib PlaceboDrug
  • RibociclibDrug
  • NSAI: Letrozole or AnastrazoleDrug
  • GoserelinDrug

Arms2

  • Experimental

    Ribociclib

    Patients in premenopausal and postmenopausal cohorts were randomized in a 1:1 ratio to either the experimental arm or the control arm. Premenopausal experimental arm: Non-steroidal aromatase inhibitor (NSAI) + Goserelin + Ribociclib. For premenopausal patients only, the patient was an adult female who was ≥ 18 years old and \< 60 years old at the time of providing informed consent. The choice of non-steroidal aromatase inhibitor was based on the investigator's assessment of the patient's past medical history. Postmenopausal experimental arm: Letrozole + Ribociclib. Pharmacokinetic (PK) Cohort: Open-label treatment with Ribociclib + Letrozole combination. For postmenopausal patients only, the patient was an adult female who was ≥ 18 years old at the time of providing informed consent.

  • Placebo comparator

    Ribociclib Placebo

    Patients in premenopausal and postmenopausal cohorts were randomized in a 1:1 ratio to either the experimental arm or the control arm. Premenopausal control arm: Non-steroidal aromatase inhibitor (NSAI) + Goserelin + Placebo. For premenopausal patients only, the patient was an adult female who was ≥ 18 years old and \< 60 years old at the time of providing informed consent. The choice of non-steroidal aromatase inhibitor was based on the investigator's assessment of the patient's past medical history. Postmenopausal control arm: Letrozole + Placebo. For postmenopausal patients only, the patient was an adult female who was ≥ 18 years old at the time of providing informed consent.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Pre and Postmenopausal Cohorts: Progressive Free Survival (PFS) Based on Local Assessment by RECIST 1.1 Guideline

    Time frame · After approximately 100 progression-free survival (PFS) events had been observed in each cohort, using data collected up to the analysis cut-off date of 25-Apr-2022, an average of 43 months.

    Registry description

    Progression-free survival (PFS) was defined as the time from randomization to the first documented disease progression or death from any cause. PFS was assessed by local investigators based on tumor evaluations using RECIST version 1.1 criteria. Patients who had not experienced progression or death by the analysis cut-off date of 25 April 2022 were censored at the date of their last adequate tumor assessment prior to that cut-off.

Secondary outcomes(9)
  1. PK Cohort: Maximum Observed Plasma Concentration (Cmax) of Ribociclib and Its Metabolite LEQ803

    Time frame · Cycle 1 Days 1/15 (0/Pre-dose, 1, 2, 4, 8 and 24 hours post-dose). 1 cycle = 28 days.

    Registry description

    Venous whole blood samples were collected for activity-based pharmacokinetic characterization. The maximum plasma concentration (Cmax) was listed and summarized using descriptive statistics. Actual sampling times were taken into consideration for the pharmacokinetic analysis.

  2. PK Cohort: Time to Maximum Observed Plasma Concentration (Tmax) of Ribociclib and Its Metabolite LEQ803

    Time frame · Cycle 1 Days 1/15 (0/Pre-dose, 1, 2, 4, 8 and 24 hours post-dose). 1 cycle = 28 days.

    Registry description

    Venous whole blood samples were collected for activity-based pharmacokinetic characterization. The time to reach maximum plasma concentration (Tmax) was listed and summarized using descriptive statistics. Actual sampling times were taken into consideration for the pharmacokinetic analysis.

  3. PK Cohort: Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours (AUC0-24h) of Ribociclib and Its Metabolite LEQ803

    Time frame · Cycle 1 Days 1/15 (0/Pre-dose, 1, 2, 4, 8 and 24 hours post-dose). 1 cycle = 28 days.

    Registry description

    Venous whole blood samples were collected for activity-based pharmacokinetic characterization. The area under the concentration-time curve from time zero to 24 hours post-dose (AUC₀-₂₄h) was listed and summarized using descriptive statistics. Actual sampling times were taken into consideration for the pharmacokinetic analysis.

  4. Pre and Postmenopausal Cohorts: Overall Survival (OS)

    Time frame · Up to approximately 80 months

    Registry description

    Overall Survival (OS) was defined as the time from date of first dose to date of death due to any cause. If a participant was not known to have died, then OS was censored at the latest date the participant was known to be alive (on or before the cut-off date).

  5. Pre and Postmenopausal Cohorts: Overall Response Rate (ORR)

    Time frame · Up to approximately 80 months

    Registry description

    Overall Response Rate (ORR) was defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR) by Investigator assessment as per RECIST 1.1 criteria: * 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.

  6. Pre and Postmenopausal Cohorts: Clinical Benefit Rate (CBR)

    Time frame · Up to approximately 80 months

    Registry description

    Clinical Benefit Rate (CBR) was defined as the proportion of patients achieving a complete response (CR) or partial response (PR) per RECIST 1.1 criteria, or stable disease (SD) lasting at least 24 weeks, based on Investigator assessment using RECIST 1.1 criteria: * 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).

  7. Pre and Postmenopausal Cohorts: Time To Response (TTR)

    Time frame · Up to approximately 80 months

    Registry description

    Time to Response (TTR) was defined as the duration from randomization to the first documented evidence of either a complete response (CR) (the disappearance of all target and non-target lesions) or a partial response (PR) (at least a 30% reduction in the sum of the longest diameters of target lesions from baseline) as assessed by the investigator.

  8. Pre and Postmenopausal Cohorts: Duration of Response (DoR)

    Time frame · Up to approximately 80 months

    Registry description

    Duration of Response (DoR) only applies to participants whose Best Overall Response (BOR) was complete response (CR) or partial response (PR) according to RECIST 1.1 based on tumor response data per local review. The start date is 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 is defined as the date of the first documented progression or death due to any cause. Participants continuing without progression or death were censored at the date of their last adequate tumor assessment.

  9. Pre and Postmenopausal Cohorts: Time to Definitive Deterioration of ECOG Performance Status From Baseline

    Time frame · Baseline up to approximately 43 months

    Registry description

    Time to definitive deterioration in ECOG performance status was defined as the time from the date of randomization to the date when ECOG performance status had definitively deteriorated by at least 1 category compared with baseline. Deterioration was considered definitive if there was no subsequent improvement in ECOG performance status back to the baseline category or above. The ECOG performance status scale assesses a patient's functional level, ranging from 0 (fully active) to 5 (dead). Patients were censored if no definitive deterioration in ECOG performance status was observed before the first to occur between: (i) the analysis cut-off date, and (ii) the date when a new anti-neoplastic therapy was started. The censoring date was the date of the last performance status assessment prior to cut-off/start of new anti-neoplastic therapy. Time to definitive deterioration of ECOG performance status from baseline was estimated by using the Kaplan-Meier method.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMedian· After approximately 100 progression-free survival (PFS) events had been observed in each cohort, using data collected up to the analysis cut-off date of 25-Apr-2022, an average of 43 months.

Pre and Postmenopausal Cohorts: Progressive Free Survival (PFS) Based on Local Assessment by RECIST 1.1 Guideline

GroupValue (Months)
Premenopausal Cohort - Ribociclib27.6
Premenopausal Cohort - Placebo14.7
Postmenopausal Cohort - RibociclibNA
Postmenopausal Cohort - Placebo18.5
Secondary and other outcome results(7)
Secondary outcomeGeometric mean· Cycle 1 Days 1/15 (0/Pre-dose, 1, 2, 4, 8 and 24 hours post-dose). 1 cycle = 28 days.

PK Cohort: Maximum Observed Plasma Concentration (Cmax) of Ribociclib and Its Metabolite LEQ803

GroupValue (ng/mL)Spread
PK Cohort - Ribociclib140042.8
Secondary outcomeMedian· Cycle 1 Days 1/15 (0/Pre-dose, 1, 2, 4, 8 and 24 hours post-dose). 1 cycle = 28 days.

PK Cohort: Time to Maximum Observed Plasma Concentration (Tmax) of Ribociclib and Its Metabolite LEQ803

GroupValue (Hour (hr))
PK Cohort - Ribociclib2.02
Secondary outcomeGeometric mean· Cycle 1 Days 1/15 (0/Pre-dose, 1, 2, 4, 8 and 24 hours post-dose). 1 cycle = 28 days.

PK Cohort: Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours (AUC0-24h) of Ribociclib and Its Metabolite LEQ803

GroupValue (ng*hr/mL)Spread
PK Cohort - Ribociclib1370041.4
Secondary outcomeMedian· Up to approximately 80 months

Pre and Postmenopausal Cohorts: Overall Survival (OS)

GroupValue (Months)
Premenopausal Cohort - Ribociclib69.2
Premenopausal Cohort - Placebo55.5
Postmenopausal Cohort - RibociclibNA
Postmenopausal Cohort - Placebo52.7
Secondary outcomeNumber· Up to approximately 80 months

Pre and Postmenopausal Cohorts: Overall Response Rate (ORR)

GroupValue (Percentage (%) of responders)
Premenopausal Cohort - Ribociclib45.6
Premenopausal Cohort - Placebo32.5
Postmenopausal Cohort - Ribociclib57.1
Postmenopausal Cohort - Placebo46.8
Secondary outcomeNumber· Up to approximately 80 months

Pre and Postmenopausal Cohorts: Clinical Benefit Rate (CBR)

GroupValue (Percentage (%) of responders)
Premenopausal Cohort - Ribociclib68.4
Premenopausal Cohort - Placebo72.7
Postmenopausal Cohort - Ribociclib83.1
Postmenopausal Cohort - Placebo76.6
Secondary outcomeMedian· Up to approximately 80 months

Pre and Postmenopausal Cohorts: Time To Response (TTR)

GroupValue (Months)
Premenopausal Cohort - Ribociclib3.7
Premenopausal Cohort - Placebo5.5
Postmenopausal Cohort - Ribociclib3.6
Postmenopausal Cohort - Placebo4.5

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Premenopausal Cohort - Ribociclib (On-treatment Period)Premenopausal Cohort - Ribociclib (On-treatment period): Events up to 30 days safety follow-up0 / 7914 / 7979 / 79
Premenopausal Cohort - Placebo (On-treatment Period)Premenopausal Cohort - Placebo (On-treatment period): Events up to 30 days safety follow-up0 / 773 / 7773 / 77
Postmenopausal Cohort - Ribociclib (On-treatment Period)Postmenopausal Cohort - Ribociclib (On-treatment period): Events up to 30 days safety follow-up1 / 7721 / 7777 / 77
Postmenopausal Cohort - Placebo (On-treatment Period)Postmenopausal Cohort - Placebo (On-treatment period): Events up to 30 days safety follow-up2 / 7716 / 7773 / 77
PK Cohort - Ribociclib (On-treatment Period)PK Cohort - Ribociclib (On-treatment period): Events up to 30 days safety follow-up0 / 175 / 1717 / 17
All Participants (On-treatment Period)All participants (On-treatment period): Events up to 30 days safety follow-up3 / 32759 / 327319 / 327
Premenopausal Cohort - Ribociclib (Post-treatment Period)Premenopausal Cohort - Ribociclib (Post-treatment period): Events in the post-treatment follow-up phase32 / 740 / 743 / 74
Premenopausal Cohort - Placebo (Post-treatment Period)Premenopausal Cohort - Placebo (Post-treatment period): Events in the post-treatment follow-up phase39 / 710 / 711 / 71
Postmenopausal Cohort - Ribociclib (Post-treatment Period)Postmenopausal Cohort - Ribociclib (Post-treatment period): Events in the post-treatment follow-up phase27 / 720 / 726 / 72
Postmenopausal Cohort - Placebo (Post-treatment Period)Postmenopausal Cohort - Placebo (Post-treatment period): Events in the post-treatment follow-up phase41 / 710 / 712 / 71
PK Cohort - Ribociclib (Post-treatment Period)PK Cohort - Ribociclib (Post-treatment period): Events in the post-treatment follow-up phase9 / 160 / 163 / 16
All Participants (Post-treatment Period)All participants (Post-treatment period): Events in the post-treatment follow-up phase148 / 3040 / 30415 / 304

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

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
Female
Age
from 18 Years up to 60 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * Patient has a histologically and/or cytologically confirmed diagnosis of estrogen receptor (ER) positive and/or progesterone receptor positive breast cancer by local laboratory (based on most recently analyzed biopsy). * Patient has HER2-negative breast cancer (based on most recently analyzed biopsy) defined as a negative in situ hybridization test or an Immunohistochemistry (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. * Patient must have either: * Measurable disease, i.e., at least 1 measurable lesion as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria (a lesion at a previously irradiated site may only be counted as a target lesion if there is a clear sign of progression since the irradiation). OR * If no measurable disease is present, then at least 1 predominantly lytic bone lesion must be present (patients with no measurable disease and only 1 predominantly lytic bone lesion that has been previously irradiated are eligible if there is documented evidence of disease progression of the bone lesion after irradiation). * Patient has ECOG performance status 0 or 1. For premenopausal cohort: * Patient is an adult, female ≥ 18 years old and \< 60 years old at the time of informed consent and has signed informed consent before any trial related activities are conducted and according to local guidelines. * Confirmed negative serum pregnancy test before starting study treatment or patient has had a hysterectomy. * Patient has advanced (loco regionally recurrent not amenable to curative therapy or metastatic) breast cancer not amenable to curative therapy (e.g. surgery and/or radiotherapy). * Patients who received ≤ 14 days of a NSAI (letrozole or anastrozole) with or without goserelin or goserelin ≤ 28 days for advanced breast cancer prior to randomization are eligible. Patients must continue treatment with the same hormonal agent + goserelin during the study. No treatment interruption is required for these patients prior to randomization. * Patients who have received up to 1 line of chemotherapy for advanced breast cancer and have been discontinued 28 days before randomization are eligible. For postmenopausal cohort: * Patient is an adult, female ≥ 18 years old at the time of informed consent and has signed informed consent before any trial related activities and according to local guidelines. * Women with advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy. Exclusion Criteria: * Patient who has received a prior CDK4/6 inhibitor. * Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgment * Patient with CNS metastases. * Patient who has not had resolution of clinical and laboratory acute toxicities related to prior anti-cancer therapy to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 Grade ≤1. * Patient has a known history of Human immunodeficiency Virus (HIV) infection (testing not mandatory). * Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality * Patient is currently receiving any of the substances as defined in the protocol that cannot be discontinued 7 days prior to the start of the treatment: For premenopausal cohort: * Pregnant or nursing (lactating) women. * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of study treatment and for 21 days after stopping study medication. Note: Use of oral (estrogen and progesterone), transdermal, injected or implanted hormonal methods of contraception as well as hormonal replacement therapy is not allowed in this study. For postmenopausal cohort: \- Patient who received any prior systemic anti-cancer therapy (including hormonal therapy and chemotherapy) for advanced breast cancer. Note: Patients who received neo (adjuvant) therapy for breast cancer are eligible. If the prior neo (adjuvant) therapy included letrozole or anastrozole, the disease free interval must be greater than 12 months from the completion of treatment until randomization. \- Patients who received ≤ 14 days of letrozole or anastrozole for advanced disease prior to randomization are eligible. Other protocol-defined inclusion/exclusion may apply.

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