Ribociclib Clinical Trials

What Is Ribociclib?

Ribociclib is an FDA-approved medication for hormone receptor-positive, HER2-negative, advanced or metastatic breast cancer. It is an orally administered drug that works as a cyclin-dependent kinase (CDK) 4/6 inhibitor. Ribociclib functions by blocking the activity of specific proteins, CDK4 and CDK6, which are crucial for cell growth and division. By inhibiting these proteins, ribociclib aims to slow or stop the proliferation of cancer cells.

Beyond its approved use, ribociclib is also being investigated in clinical trials for other conditions. These include various stages of breast cancer, such as early high-risk HR+HER2- breast cancer, and other types of cancer like glioblastoma and diffuse intrinsic pontine glioma. The drug is often studied in combination with other therapies, such as aromatase inhibitors or endocrine therapy, to enhance its effectiveness.

Uses and Conditions Under Study

Ribociclib is primarily studied for various forms of breast cancer, reflecting its FDA approval and ongoing research. It is being investigated in **54 trials** for general breast cancer, **20 trials** for metastatic breast cancer, and **10 trials** for advanced breast cancer. Specific subtypes, including HER2-negative breast cancer (**7 trials**), ER-positive breast cancer (**3 trials**), and HR+/HER2- breast cancer (**3 trials**), are also under active investigation. As a CDK4/6 inhibitor, ribociclib helps regulate the cell cycle, which is often disrupted in breast cancer, aiming to slow tumor growth and improve patient outcomes. Studies are also exploring its real-world effectiveness and alternative dosing strategies for older patients with metastatic breast cancer to improve tolerability.

Ribociclib is also being explored for its potential in treating aggressive brain tumors. It is currently under study in **4 trials** for glioblastoma and **3 trials** for diffuse intrinsic pontine glioma. These are challenging cancers, particularly in pediatric populations, where ribociclib's cell cycle inhibiting properties may offer a new therapeutic approach. Research includes evaluating its safety and efficacy in children and young adults with brain tumors, often in combination with other chemotherapy or radiation therapies.

Dosing

Ribociclib is an orally administered medication, typically taken as tablets. The standard adult dose often involves **600 mg** once daily for 3 weeks, followed by 1 week off, in combination with an aromatase inhibitor such as letrozole, anastrozole, or exemestane. This cyclical dosing schedule is designed to manage potential side effects while maximizing therapeutic benefit.

Investigational dosing strategies are also being explored. For older patients (age ≥ 65 years) with metastatic breast cancer, studies are evaluating alternative dosing regimens, including **400 mg** of ribociclib, to improve tolerability and allow patients to remain on treatment longer. Ribociclib has also been studied at various strengths, including **100 mg**, **200 mg**, and **300 mg**, when used in combination with other investigational drugs like ceritinib or enzalutamide.

For pediatric patients and young adults with brain tumors, ribociclib is being studied at different investigational dose levels. These studies aim to determine the appropriate and safest doses when ribociclib is combined with other treatments like topotecan and temozolomide, or everolimus, for conditions such as glioblastoma and diffuse intrinsic pontine glioma.

Side Effects

The most common side effect reported in clinical trials for Ribociclib was neutropenia, a condition characterized by a low count of a type of white blood cell. In studies involving 1185 to 1267 patients, 59.7% of patients taking Ribociclib experienced neutropenia, compared to 5.4% of patients on placebo. Decreased neutrophil count was also reported in 26.8% of patients on Ribociclib versus 1.8% on placebo.

Other common side effects reported by patients taking Ribociclib, compared to those on placebo, included:

• Nausea: 45.1% on Ribociclib versus 28.5% on placebo.
• Fatigue: 35.9% on Ribociclib versus 30.9% on placebo.
• Arthralgia (joint pain): 35.3% on Ribociclib versus 37.5% on placebo.
• Diarrhea: 32.9% on Ribociclib versus 22.0% on placebo.
• Vomiting: 26.9% on Ribociclib versus 16.5% on placebo.
• Alopecia (hair loss): 24.5% on Ribociclib versus 11.6% on placebo.

Less common side effects included headache (26.8% on Ribociclib vs 22.8% on placebo), cough (24.5% on Ribociclib vs 17.7% on placebo), constipation (24.3% on Ribociclib vs 16.3% on placebo), and back pain (23.5% on Ribociclib vs 20.5% on placebo).

Clinical Trial Results

Ribociclib for Postmenopausal Women with Advanced Breast Cancer

In a study (NCT01958021) involving postmenopausal women with advanced breast cancer, Ribociclib combined with letrozole significantly improved overall survival. Patients receiving Ribociclib plus letrozole had a median overall survival of 63.9 months, compared to 51.4 months for those receiving placebo plus letrozole. The overall response rate (ORR), which measures the percentage of patients whose cancer shrinks or disappears, was 40.7% for the Ribociclib group versus 27.5% for the placebo group. The clinical benefit rate (CBR), indicating patients who experienced a complete response, partial response, or stable disease for at least 24 weeks, was 79.6% for Ribociclib plus letrozole, compared to 72.8% for placebo plus letrozole. The median time until a definitive 10% worsening in global health status/quality of life was 19.3 months for patients on Ribociclib plus letrozole, with data not available for the placebo group.

Ribociclib for Premenopausal Women with Advanced Breast Cancer

A study (NCT02278120) in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer evaluated Ribociclib combined with an NSAI/tamoxifen and goserelin. The median progression-free survival (PFS), the time patients lived without their cancer getting worse, was 23.8 months for the Ribociclib combination, significantly longer than 13.0 months for the placebo combination. The overall response rate (ORR) was 40.9% for the Ribociclib group compared to 29.7% for the placebo group. The clinical benefit rate (CBR) was 79.1% for the Ribociclib combination versus 69.7% for the placebo combination. The median duration of response (DOR) was 21.3 months with Ribociclib, compared to 17.5 months with placebo.

Ribociclib for Men and Postmenopausal Women with Advanced Breast Cancer

In a study (NCT02422615) involving men and postmenopausal women with advanced breast cancer, Ribociclib combined with fulvestrant was assessed. The median progression-free survival (PFS) as assessed by investigators was 20.5 months for the Ribociclib plus fulvestrant group, compared to 12.8 months for the placebo plus fulvestrant group. The overall response rate (ORR) was 32.4% for the Ribociclib combination, versus 21.5% for the placebo combination. The clinical benefit rate (CBR) was 70.2% for patients on Ribociclib plus fulvestrant, compared to 62.8% for those on placebo plus fulvestrant.

Ribociclib for Advanced Neuroendocrine Tumors

A study (NCT02420691) investigated Ribociclib in patients with advanced neuroendocrine tumors of foregut origin. The median progression-free survival (PFS) was 10.44 months. Clinical benefit, defined as a complete response, partial response, or stable disease, was observed in 19 participants. A response rate, indicating tumor shrinkage, was also observed in 19 participants.

Currently Recruiting Trials

Clinical trials for Ribociclib are actively seeking participants to explore new ways to use this medication, often in combination with other treatments, for various types of cancer. These studies aim to understand the safety and effectiveness of Ribociclib in different settings, from early-stage disease to advanced conditions.

• A Phase II study, NCT07405801, sponsored by Hoffmann-La Roche, is recruiting approximately 80 participants with advanced breast cancer. This trial evaluates the efficacy and safety of a triplet combination of inavolisib, ribociclib, and fulvestrant compared to a placebo plus ribociclib and fulvestrant in those with endocrine-therapy-resistant hormone receptor-positive, HER2-negative breast cancer.
• For individuals with hormone receptor-positive, HER2-negative early breast cancer that has residual disease after initial chemotherapy, a Phase III study, NCT07400523, is enrolling 446 participants. This trial, sponsored by Sun Yat-Sen Memorial Hospital, investigates adjuvant ribociclib combined with an aromatase inhibitor.
• Another Phase III study, NCT07237256, led by UNICANCER, is recruiting a large group of 3902 participants. This trial focuses on chemotherapy de-escalation in HR+, HER2-, intermediate-risk early breast cancer treated with adjuvant ribociclib.
• Olema Pharmaceuticals, Inc. is sponsoring a Phase III trial, NCT07085767, for 1000 participants with ER+/HER2- advanced breast cancer. This study compares palazestrant in combination with ribociclib to letrozole and ribociclib as a first-line treatment.
• A non-interventional study, NCT06930859, by Novartis Pharmaceuticals, is observing the effectiveness and safety of ribociclib in the adjuvant therapy of hormone receptor-positive, HER2-negative Stage II and III breast cancer in real clinical practice in Russia. This study aims to enroll 2766 participants.
• Beyond breast cancer, a Phase II study, NCT05843253, at Nationwide Children's Hospital, is enrolling 120 participants. This trial evaluates ribociclib and everolimus in high-grade glioma and diffuse intrinsic pontine glioma, or ribociclib and temozolomide in diffuse hemispheric glioma with H3 G34-mutant.

Where to Participate

Clinical trials for Ribociclib are broadly available, offering opportunities for participation across the United States and internationally. There are currently 679 study sites located in 376 cities across 48 states. The cities with the highest number of recruiting sites include Boston, Massachusetts (31 sites); New York, New York (26 sites); Los Angeles, California (22 sites); Houston, Texas (20 sites); and St Louis, Missouri (19 sites).

Eligibility for these trials generally includes individuals aged 0-100 years, encompassing all genders. Healthy volunteers are typically not eligible for these studies, but children are welcome to participate in relevant trials.

Development Timeline

The clinical development of Ribociclib began on May 20, 2013, marking the start of its journey through various research phases. Since then, a total of 159 clinical trials have been initiated, enrolling nearly 70,000 participants. The latest trial is projected to conclude on March 25, 2026, indicating ongoing research and innovation.

Initially, early investigations explored conditions such as IBS-C and hyperphosphatemia. However, the primary focus quickly expanded to advanced breast cancer, particularly hormone receptor-positive, HER2-negative types. Over time, the pipeline broadened to include early breast cancer, breast neoplasms, glioblastoma, and various other solid tumors, demonstrating the drug's versatile potential.

Novartis Pharmaceuticals has been the leading sponsor, driving 36 of these trials. Other key sponsors, including AstraZeneca, Hoffmann-La Roche, and Pfizer, have also contributed significantly to the research landscape. The development journey has progressed through various phases, with 43 Phase II trials, 37 Phase I trials, and 30 Phase III trials, alongside other phases, reflecting a comprehensive approach to understanding Ribociclib's role in cancer treatment.