Ribociclib Combination Therapy for Breast Cancer

Recruiting at 69 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Novartis Pharmaceuticals

Must be taking: Ribociclib

Disqualifiers: Unresolved toxicities, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 years

137 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label, multi-center, roll-over study to evaluate the long term safety of ribociclib in combination with other drugs in participants who are participating in a Novartis sponsored global study, that has fulfilled requirements for its primary objective(s), and who in the opinion of the Investigator, would benefit from continued treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, since it involves continuing ribociclib treatment from a previous study, you may need to stay on this medication.

What data supports the effectiveness of the drug Ribociclib in combination with other therapies for breast cancer?

Research from the MONALEESA-2 study shows that combining Ribociclib with Letrozole significantly improves progression-free survival (the time during and after treatment that a patient lives with the disease without it getting worse) in patients with hormone receptor-positive, HER2-negative advanced breast cancer compared to Letrozole alone. ^{1 2 3 4 5}

Is Ribociclib combination therapy safe for humans?

Ribociclib, when combined with letrozole, has been shown to have a manageable safety profile in treating advanced breast cancer. Common side effects include low white blood cell counts, nausea, tiredness, diarrhea, hair loss, vomiting, constipation, headache, and back pain. ^{1 5 6 7 8}

How is the Ribociclib combination drug unique for breast cancer treatment?

The Ribociclib combination drug is unique because it includes Ribociclib, a cyclin-dependent kinase 4/6 inhibitor, which when combined with letrozole, significantly improves progression-free survival in patients with hormone receptor-positive, HER2-negative advanced breast cancer, offering a substantial clinical benefit compared to letrozole alone. ^{1 2 3 4 6}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

This trial is for breast cancer patients already in a Novartis study, who've seen benefits from Ribociclib and other drugs. They must have completed at least 6 cycles of treatment with Ribociclib. Those permanently off Ribociclib or with unresolved toxicities from it can't join.

Inclusion Criteria

Currently participating in a Novartis sponsored global study (parent study), receiving treatment with ribociclib in combination with other drugs, and the parent study has fulfilled its primary objective(s)

I have been treated with ribociclib for at least 6 cycles.

You are currently benefiting from the treatment according to the doctor.

Exclusion Criteria

I had to stop taking ribociclib due to side effects that haven't gone away.

I was permanently taken off ribociclib in a previous study.

I can get and afford ribociclib where I live.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants continue receiving ribociclib in combination with other drugs as in the parent study

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Anastrozole
• Fulvestrant
• Goserelin
• Letrozole
• Ribociclib
• Tamoxifen

Trial Overview The study tests the long-term safety of continued use of Ribociclib combined with Letrozole, Anastrozole, Goserelin, Tamoxifen, or Fulvestrant in those benefiting from it after completing primary objectives in an earlier Novartis trial.

Participant Groups

Group I: Ribociclib Experimental Treatment 6 Interventions

All participants will receive ribociclib in combination with other drugs at the same dose/schedule as in the parent study.

Anastrozole is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Arimidex for:

• Breast cancer
• Early breast cancer in postmenopausal women

Approved in United States as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer

Approved in Canada as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• Treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Approved in Japan as Arimidex for:

• Breast cancer

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

In the MONALEESA-7 trial involving 672 premenopausal women with advanced HR-positive breast cancer, ribociclib combined with endocrine therapy significantly improved progression-free survival (23.8 months) compared to placebo (13.0 months), indicating its efficacy as a first-line treatment option.

The safety profile of ribociclib was manageable, with common grade 3 or 4 adverse events like neutropenia occurring in 61% of patients, but no treatment-related deaths were reported, suggesting that while there are risks, the benefits may outweigh them for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Tripathy, D., Im, SA., Colleoni, M., et al.[2022]

In the MONALEESA-2 study involving 213 US patients with hormone receptor-positive, HER2-negative advanced breast cancer, ribociclib combined with letrozole significantly improved progression-free survival (PFS) to 27.6 months compared to 15.0 months with letrozole alone, indicating its efficacy as a first-line treatment.

The most common side effects of ribociclib included neutropenia (72%), nausea (69%), and fatigue (60%), highlighting the importance of monitoring for these adverse events during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Ribociclib With Letrozole in US Patients Enrolled in the MONALEESA-2 Study. Yardley, DA., Hart, L., Favret, A., et al.[2020]

Ribociclib, when combined with letrozole, has shown significant efficacy in treating hormone receptor positive (HR+) and HER2-negative advanced breast cancer, as evidenced by a complete clinical response in a postmenopausal patient with aggressive disease after just three months of treatment.

The treatment was well tolerated with minimal side effects, and the patient maintained a complete response for 15 months, highlighting the potential for long-lasting benefits in managing advanced breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete Clinical Response in Locally Advanced Metastatic de novo Breast Cancer after Front-Line Treatment with Ribociclib/Letrozole within the RIBANNA Study. Rudlowski, C., Beermann, N., Leitzen, L., et al.[2022]

In the phase 3 MONALEESA-2 study involving 668 postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, the combination of ribociclib (RIB) and letrozole (LET) significantly improved the duration of response (DoR) to 26.7 months compared to 18.6 months with placebo plus LET.

Patients receiving RIB also experienced greater tumor shrinkage and pain reduction, with 32% showing a significant tumor response at 8 weeks, reinforcing the efficacy of RIB plus LET as a first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line ribociclib plus letrozole in postmenopausal women with HR+ , HER2- advanced breast cancer: Tumor response and pain reduction in the phase 3 MONALEESA-2 trial. Janni, W., Alba, E., Bachelot, T., et al.[2019]

In the MONALEESA-2 study involving 668 postmenopausal women with advanced breast cancer, ribociclib combined with letrozole significantly improved progression-free survival (PFS) to 25.3 months compared to 16.0 months for placebo plus letrozole, demonstrating a strong treatment benefit.

The safety profile of ribociclib plus letrozole remained manageable over an extended follow-up period, with no new toxicities reported, indicating that this combination therapy is both effective and safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Hortobagyi, GN., Stemmer, SM., Burris, HA., et al.[2022]

In a study of 554 Italian patients with hormone receptor-positive, HER2-negative advanced breast cancer, ribociclib combined with letrozole showed a clinical benefit rate of 71.7% and a median time to progression of 26.7 months, indicating effective treatment outcomes.

The treatment was associated with manageable safety profiles, with 98.9% of patients experiencing all-grade adverse events, primarily neutropenia, but health-related quality of life scores remained stable during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Ribociclib in Combination with Letrozole in Patients with HR+, HER2- Advanced Breast Cancer: Results from the Italian Subpopulation of Phase 3b CompLEEment-1 Study. De Laurentiis, M., Caputo, R., Mazza, M., et al.[2022]

Ribociclib, approved by the FDA for treating advanced breast cancer, significantly improves progression-free survival when combined with letrozole compared to a placebo, as shown in a study of 668 patients.

The overall response rate for patients receiving ribociclib plus letrozole was 52.7%, compared to 37.1% for those on placebo, indicating its efficacy, although common side effects included neutropenia and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval: Ribociclib for the Treatment of Postmenopausal Women with Hormone Receptor-Positive, HER2-Negative Advanced or Metastatic Breast Cancer. Shah, A., Bloomquist, E., Tang, S., et al.[2019]

Ribociclib, a CDK 4/6 inhibitor, significantly improves median progression-free survival (PFS) in women with HR+/HER2- metastatic breast cancer when used in combination with endocrine therapy, with PFS ranging from 8 to 13 months across three phase III trials.

The treatment is well tolerated, particularly in elderly patients, and while it has some dose-limiting toxicities like neutropenia and QTc prolongation, it maintains health-related quality of life and reduces pain scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ribociclib in HR+/HER2- Advanced or Metastatic Breast Cancer Patients. Rascon, K., Flajc, G., De Angelis, C., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Ribociclib With Letrozole in US Patients Enrolled in the MONALEESA-2 Study. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Complete Clinical Response in Locally Advanced Metastatic de novo Breast Cancer after Front-Line Treatment with Ribociclib/Letrozole within the RIBANNA Study. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

First-line ribociclib plus letrozole in postmenopausal women with HR+ , HER2- advanced breast cancer: Tumor response and pain reduction in the phase 3 MONALEESA-2 trial. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. [2022]

6. France pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Ribociclib in Combination with Letrozole in Patients with HR+, HER2- Advanced Breast Cancer: Results from the Italian Subpopulation of Phase 3b CompLEEment-1 Study. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

FDA Approval: Ribociclib for the Treatment of Postmenopausal Women with Hormone Receptor-Positive, HER2-Negative Advanced or Metastatic Breast Cancer. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Ribociclib in HR+/HER2- Advanced or Metastatic Breast Cancer Patients. [2020]