Abemaciclib for Cancer

Overseen By Geoffrey Shapiro, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: CDK4/6 inhibitors, TKIs

Disqualifiers: Hematologic lymphoma, CNS metastases, HIV, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 months

38 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is studying a targeted therapy as a possible treatment for cancer abnormality in one of the following genes: CCND1, CCND2, CCND3, CDK4, or CDK6. The drug involved in this study is: -Abemaciclib

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot have had chemotherapy, biologic therapy, investigational agents, or major surgery within 4 weeks before starting the study. Also, you cannot be on enzyme-inducing antiepileptic drugs unless you can switch to a different type before starting the trial.

What data supports the effectiveness of the drug Abemaciclib for cancer?

Abemaciclib, when used with endocrine therapy, has been shown to reduce the risk of breast cancer coming back in patients with certain types of early breast cancer. It is also effective as a first-line treatment for advanced breast cancer, improving the time patients live without the disease getting worse. ^{1 2 3 4 5}

How is the drug Abemaciclib unique in treating cancer?

Abemaciclib is unique because it is an oral medication that specifically targets and inhibits cyclin-dependent kinases 4 and 6 (CDK4/6), which are proteins involved in cell division. This makes it effective in treating certain types of breast cancer, especially when combined with other therapies, and it is being explored for use in other cancers as well. ^{1 3 4 6 7}

Research Team

Geoffrey I. Shapiro

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Adults with advanced solid tumors not originating from breast tissue, who have specific genetic alterations in CCND1/2/3 or CDK4/6 and no standard treatment options left. They must be physically capable of taking oral medication, have stable vital organ functions, and agree to use contraception. Excluded are those with recent treatments, certain metastases, active hepatitis B/C or HIV, pregnant or breastfeeding women.

Inclusion Criteria

I can swallow and keep down pills.

My advanced cancer is not breast cancer and standard treatments no longer work or don't exist for it.

My cancer has a high level of CDK4 or CDK6, confirmed by a specific test.

Exclusion Criteria

I have brain metastases causing symptoms and need radiation.

Participants with known HIV-positive status

I have fully recovered from any side effects of previous treatments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Abemaciclib orally on a daily basis

4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Abemaciclib

Trial Overview The trial is testing Abemaciclib's effectiveness on cancers with certain gene abnormalities. Participants will receive this targeted therapy orally. The study includes two arms based on different genetic alterations related to cyclins D1/D2/D3 and CDK4/6 amplification.

Participant Groups

Group I: Participants with CDK4 or CDK6 Experimental Treatment 1 Intervention

* Abemaciclib will be administered orally on a daily basis * Dosage will be determine by the PI

Group II: Participants with CCND1, CCND2, or CCND3 Experimental Treatment 1 Intervention

* Abemaciclib will be administered orally on a daily basis * Dosage will be determine by the PI

Abemaciclib is already approved in United States, European Union for the following indications:

Approved in United States as Verzenio for:

• Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Approved in European Union as Verzenio for:

• HR+, HER2- advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Findings from Research

In a phase III trial, abemaciclib combined with endocrine therapy significantly reduced the risk of breast cancer recurrence in patients with hormone receptor positive (HR+), HER2-negative, node-positive early breast cancer, regardless of prior chemotherapy or tumor characteristics.

The combination treatment was generally well-tolerated, with manageable side effects such as diarrhea, infections, and neutropenia, making it a valuable option for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. Fung, S., Blair, HA.[2023]

Interim results from the MONARCH3 study show that abemaciclib, a CDK4/6 inhibitor, is an effective first-line treatment for advanced ER-positive, HER2-negative breast cancer.

Patients receiving abemaciclib in combination with letrozole experienced significantly improved progression-free survival compared to those receiving a placebo with endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019]

A new ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to effectively monitor abemaciclib levels in patients with advanced breast cancer, showing high accuracy and precision in quantification.

This method allows for robust therapeutic drug monitoring (TDM) of abemaciclib, which can help personalize treatment and improve adherence in patients, addressing challenges in the emerging field of oral antitumor therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An UHPLC-MS/MS method for quantification of the CDK4/6 inhibitor abemaciclib in human serum. Habler, K., Vogeser, M., Teupser, D.[2022]

Abemaciclib is an oral medication that inhibits cyclin-dependent kinases 4 and 6, specifically approved in the USA for treating advanced or metastatic breast cancer that is hormone receptor-positive and HER2-negative.

It is effective both as a combination therapy with fulvestrant for patients who have progressed after endocrine therapy and as a standalone treatment for those who have also undergone chemotherapy, highlighting its role in advanced cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: First Global Approval. Kim, ES.[2019]

Abemaciclib combined with endocrine therapy (ET) significantly improves quality-adjusted life years (QALYs) in patients with high-risk hormone receptor positive, HER2-negative early breast cancer, with an increase of 0.99 QALYs compared to ET alone.

The treatment is considered cost-effective in Italy, with an incremental cost-effectiveness ratio of €22,651 per QALY gained, and a 99% likelihood of being cost-effective at a threshold of €30,000 per QALY.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of abemaciclib with endocrine therapy (ET) versus ET alone for HR+, HER2-, node-positive, high-risk early breast cancer in Italy. Davie, A., Traoré, S., Giovannitti, M., et al.[2023]

Abemaciclib is a potent oral CDK4 and CDK6 inhibitor that effectively treats hormone receptor-positive, HER2-negative advanced or metastatic breast cancer, showing response rates between 19.7% and 59% in major clinical trials.

The drug is well-tolerated, with common side effects including diarrhea and neutropenia, and it offers the advantage of continuous dosing and potential use as a monotherapy, making it a promising option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: The Newest CDK4/6 Inhibitor for the Treatment of Breast Cancer. Palumbo, A., Lau, G., Saraceni, M.[2020]

In a phase 1b study involving 50 patients with advanced non-small cell lung cancer (NSCLC), the combination of abemaciclib and pembrolizumab showed significant toxicity, with 80% of patients in cohort A and 76% in cohort B experiencing severe treatment-emergent adverse events.

Despite some antitumor activity, including a disease control rate of 56% in cohort A and 64% in cohort B, the overall risk-benefit profile of this combination therapy does not support further investigation in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study. Pujol, JL., Vansteenkiste, J., Paz-Ares Rodríguez, L., et al.[2022]

References

1. France pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. [2023]

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

First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

An UHPLC-MS/MS method for quantification of the CDK4/6 inhibitor abemaciclib in human serum. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Abemaciclib: First Global Approval. [2019]

5. Italy pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of abemaciclib with endocrine therapy (ET) versus ET alone for HR+, HER2-, node-positive, high-risk early breast cancer in Italy. [2023]

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

Abemaciclib: The Newest CDK4/6 Inhibitor for the Treatment of Breast Cancer. [2020]

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

Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study. [2022]