Ribociclib + Endocrine Therapy for Breast Cancer

(NATALEE Trial)

Not currently recruiting at 562 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: Endocrine therapy

Must not be taking: CDK4/6 inhibitors, Tamoxifen

Disqualifiers: Metastases, HIV, Hepatitis, others

Stay on Your Current Meds You can continue your current medications while participating

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 60 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of ribociclib (Kisqali) combined with endocrine therapy for treating early-stage, hormone receptor-positive (HR+) and HER2-negative breast cancer. Participants will receive either ribociclib with endocrine therapy or endocrine therapy alone. Ideal candidates have undergone surgery to remove breast cancer, show no signs of cancer spreading, and have hormone receptor-positive, HER2-negative breast cancer. As a Phase 3 trial, it represents the final step before FDA approval, providing participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, especially those that strongly affect liver enzymes (CYP3A4/5) or have a narrow safety margin. If you're on hormone replacement therapy or certain cancer prevention drugs, you may need to stop those as well.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ribociclib, when combined with hormone therapy, is generally well-tolerated by patients with HR+/HER2- early breast cancer. Most side effects from ribociclib can be managed by adjusting the dose, allowing many patients to continue treatment. This suggests it is relatively safe for use.

Hormone therapy alone has long been a standard treatment for hormone receptor-positive breast cancer, indicating its safety for treating this type of cancer.

Overall, both treatments have demonstrated safety, with ribociclib's side effects being manageable and hormone therapy already established as a safe standard treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ribociclib combined with endocrine therapy is unique because it targets the growth of cancer cells in a new way. Unlike standard treatments for breast cancer, which often rely solely on endocrine therapy to block hormones that fuel cancer growth, ribociclib is a CDK4/6 inhibitor. This means it specifically interrupts the cycle that cancer cells use to divide and multiply. Researchers are excited about this combination because it has the potential to enhance the effectiveness of endocrine therapy, offering a more powerful option for slowing the progression of the disease.

What evidence suggests that ribociclib with endocrine therapy could be an effective treatment for early breast cancer?

Research has shown that combining ribociclib with hormone therapy, which participants in this trial may receive, greatly improves outcomes for patients with HR+/HER2- early breast cancer. Studies have found that this combination helps patients live longer without cancer recurrence for at least five years. It also significantly delays cancer progression compared to other treatments. Overall, ribociclib plus hormone therapy appears to provide better long-term outcomes for patients with this type of breast cancer. Another group in this trial will receive endocrine therapy alone, serving as an active comparator. ^{2 4 6 7 8}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults with early-stage, hormone receptor-positive (HR+), HER2-negative breast cancer who've had surgery to remove the tumor and possibly chemotherapy or radiotherapy if needed. They should be in good physical condition (ECOG 0 or 1) and not have any severe medical conditions that could interfere with the trial. People can't join if they're pregnant, breastfeeding, have HIV/Hepatitis B/C, are on certain drugs affecting liver enzymes, or have had another cancer within the last two years.

Inclusion Criteria

I have finished all recommended chemotherapy before or after surgery.

I was diagnosed with invasive breast cancer less than 18 months ago.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I am still experiencing side effects from my previous cancer treatments.

Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical trial or compromise compliance with the protocol

I have a digestive issue that affects how my body absorbs medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ribociclib 400 mg once daily on days 1-21 of a 28-day cycle and endocrine therapy once daily continuously

60 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 91 months

What Are the Treatments Tested in This Trial?

Interventions

• Endocrine Therapy
• Ribociclib

Trial Overview

The study is testing how well Ribociclib works alongside standard endocrine therapy as an additional treatment after surgery for breast cancer. It's a phase III trial where patients are randomly assigned to receive either this combination treatment or just endocrine therapy alone to compare effectiveness and safety.

How Is the Trial Designed?

Group I: Ribociclib + Endocrine Therapy Experimental Treatment 2 Interventions

Participants will receive ribociclib 400 mg once daily on days 1-21 of a 28-day cycle and endocrine therapy once daily continuously

Group II: Endocrine Therapy Active Control 1 Intervention

Participants will receive endocrine therapy only once daily continuously

Endocrine Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Hormone Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Approved in United States as Hormone Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Approved in Canada as Hormone Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Approved in Japan as Hormone Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Approved in China as Hormone Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Approved in Switzerland as Hormone Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian 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

Translational Research in Oncology

Collaborator

Trials

22

Recruited

6,700+

Published Research Related to This Trial

Ribociclib has been approved by the FDA for use in male patients with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer, showing an overall response rate of 46.9% in a clinical trial with 39 male patients.

The safety profile of ribociclib in male patients is similar to that observed in female patients, indicating that its efficacy and safety are consistent across genders when used in combination with aromatase inhibitors or fulvestrant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Ribociclib Indicated for Male Patients with Hormone Receptor-Positive, HER2-Negative Advanced or Metastatic Breast Cancer. Gao, JJ., Osgood, CL., Feng, Z., et al.[2023]

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]

Ribociclib, a CDK 4/6 inhibitor, has been shown to significantly improve progression-free survival in patients with hormone receptor-positive, HER2-negative advanced breast cancer when used in combination with letrozole, based on the results of the MONALEESA-2 phase 3 trial involving a randomized, double-blind design.

The study highlights ribociclib's effectiveness across various patient subgroups, including those with different ages and disease histories, establishing it as a valuable treatment option for managing advanced breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ribociclib for the first-line treatment of advanced hormone receptor-positive breast cancer: a review of subgroup analyses from the MONALEESA-2 trial. Hortobagyi, GN.[2019]

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 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]

The combination of antiestrogen therapy and ribociclib, a CDK4/6 inhibitor, significantly improved progression-free survival in women with metastatic HR-positive, HER2-negative breast cancer compared to letrozole alone.

These findings come from a large phase III trial, which may support FDA approval for this combination treatment, highlighting its potential efficacy in managing this type of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ribociclib Lengthens Breast Cancer Survival. [2018]

In the phase III MONALEESA-7 trial, ribociclib combined with endocrine therapy significantly improved overall survival (OS) in pre-/perimenopausal patients with hormone receptor-positive, HER2-negative advanced breast cancer, with a median OS of 58.7 months compared to 48.0 months for the placebo group.

The study included 672 patients and showed that ribociclib not only delayed the time to first chemotherapy but also had consistent OS benefits across various subgroups, including those under 40 years old, indicating its efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Lu, YS., Im, SA., Colleoni, M., et al.[2023]

Ribociclib, when combined with letrozole or fulvestrant, has shown improved progression-free survival and overall survival in postmenopausal women with hormone receptor-positive breast cancer, based on a Phase III study involving 668 participants.

While ribociclib is effective, it has a higher risk of liver function abnormalities and can cause QTc prolongation, making it less suitable for patients with certain cardiac conditions; alternative CDK 4/6 inhibitors like palbociclib or abemaciclib may be safer options in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ribociclib in the Treatment of Hormone-Receptor Positive/HER2-Negative Advanced and Early Breast Cancer: Overview of Clinical Data and Patients Selection. Parati, MC., Pedersini, R., Perego, G., et al.[2022]

Ribociclib is an oral medication that inhibits CDK 4 and 6, leading to cell cycle arrest in cancer cells, and has been approved in the USA for treating advanced breast cancer in combination with an aromatase inhibitor.

The drug is currently undergoing further phase III trials for breast cancer and is being tested in early-phase trials for other types of solid tumors and blood cancers, highlighting its potential as a versatile cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ribociclib: First Global Approval. Syed, YY.[2018]

Ribociclib, a CDK4/6 inhibitor used in treating hormone receptor-positive metastatic breast cancer, was associated with a rare case of grade 3 acute kidney injury (AKI) in an elderly woman, leading to treatment discontinuation after recurrence upon re-initiation.

While previous studies (MONALEESA 2-3-7) reported no severe AKI cases causing treatment discontinuation, this case highlights the potential for serious kidney-related side effects, suggesting that close monitoring of kidney function is necessary during ribociclib therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ribociclib induced acute kidney injury: A case report. Gulturk, I., Yilmaz, M., Ozmen, A., et al.[2022]

Citations

1.

jamanetwork.com

jamanetwork.com/journals/jamaoncology/fullarticle/2839158

Ribociclib Plus Endocrine Therapy in Hormone Receptor ...

Importance Ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) has demonstrated a statistically significant invasive disease-free survival ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12464853/

Ribociclib Plus Endocrine Therapy in Hormone Receptor ...

Ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) has demonstrated a statistically significant invasive disease-free survival (iDFS) ...

3.

us.kisqali.com

us.kisqali.com/metastatic-breast-cancer/proven-results/results-with-kisqali

Clinical Trial Results | mBC | KISQALI® (ribociclib)

Review clinical trial results in women living with HR+, HER2- metastatic breast cancer who were treated with KISQALI. See full Prescribing and Safety Info.

4.

esmoopen.com

esmoopen.com/article/S2059-7029(25)01727-2/fulltext

Adjuvant ribociclib plus nonsteroidal aromatase inhibitor ...

This 5-year follow-up of efficacy outcomes from NATALEE demonstrated persistent iDFS, DDFS, DRFS, and RFS benefit over time in patients with ...

5.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.24.00144

Final Results of RIGHT Choice: Ribociclib Plus Endocrine ...

First-line ribociclib plus ET showed a significant PFS benefit, similar response rates, and better tolerability over combination CT in patients with clinically ...

6.

novartis.com

novartis.com/us-en/news/media-releases/novartis-kisqali-5-year-natalee-data-demonstrate-28-reduction-risk-recurrence-broadest-early-breast-cancer-patient-population

Novartis Kisqali® 5-year NATALEE data demonstrate 28% ...

Novartis Kisqali® 5-year NATALEE data demonstrate 28% reduction in risk of recurrence in the broadest early breast cancer patient population.

7.

kisqali-hcp.com

kisqali-hcp.com/early-breast-cancer/safety

Safety | eBC | KISQALI® (ribociclib)

With KISQALI, most adverse reactions were manageable and reversible with dose reduction, which may have helped patients remain on therapy.

8.

onclive.com

onclive.com/view/adjuvant-ribociclib-plus-ai-therapy-has-long-term-activity-in-hr-her2-negative-early-breast-cancer

Adjuvant Ribociclib Plus AI Therapy Has Long-Term ...

Ribociclib plus AI significantly improved iDFS in hormone receptor–positive, HER2-negative early breast cancer patients compared to AI alone, ...