Abemaciclib for Brain Cancer

Recruiting at 9 trial locations

Overseen By Ingo Mellinghoff, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Antiretrovirals, EIAEDs

Disqualifiers: Intracranial hemorrhage, Active infection, 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: Until disease progression or unacceptable toxicity

64 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a drug called abemaciclib in patients whose brain tumors have come back after treatment. The drug aims to stop the growth of cancer cells by blocking certain proteins that help them multiply. Researchers want to see both the positive and negative effects of this treatment. Abemaciclib is used primarily for treating metastatic breast cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that no other investigational or standard anti-tumor therapy is allowed. Additionally, patients must not be on enzyme-inducing antiepileptic drugs (EIAEDs) and must abstain from grapefruit juice.

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

Research shows that Abemaciclib, a drug that blocks certain proteins (CDK4/6 inhibitors), can cross the blood-brain barrier and increase survival in animal models with brain tumors. It has also shown promise in treating other cancers, like breast cancer, by slowing disease progression. ^{1 2 3 4 5}

What makes the drug Abemaciclib unique for treating brain cancer?

Abemaciclib is unique for brain cancer treatment because it can cross the blood-brain barrier more efficiently than similar drugs, potentially allowing it to target brain tumors more effectively at lower doses. ^{1 4 6 7 8}

Research Team

Thomas Kaley, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with recurrent brain tumors, specifically IDH wildtype and RB intact gliomas or other primary brain tumors. Participants must have had prior therapy, be able to swallow pills, consent to use birth control, and not be on certain medications or have specific health conditions that could interfere with the study.

Inclusion Criteria

You are expected to live for more than 8 weeks.

My brain tumor has returned despite treatment and is IDH mutant.

My glioma has been or will be tested for specific genetic changes.

Exclusion Criteria

I have had multiple treatments for my condition.

You cannot drink grapefruit juice while participating in the study.

I have a history of fainting due to heart issues, irregular heartbeats, or sudden cardiac arrest.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abemaciclib for recurrent brain tumors, with some patients undergoing pre-surgical treatment

Until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Abemaciclib

Trial Overview The trial is testing abemaciclib (LY2835219) effects on patients with recurrent brain tumors. It aims to understand both the potential benefits and adverse reactions of this drug in individuals who have seen their tumor return after initial treatment.

Participant Groups

Group I: C:All other recurrent brain tumors Experimental Treatment 1 Intervention

This is an exploratory cohort including patients with recurrent IDH mutant glioma, meningioma, recurrent ependymoma, and recurrent PCNSL,and other primary brain tumors.

Group II: B:Recurrent glioma any grade Experimental Treatment 1 Intervention

Ten patients who require standard of care cytoreductive surgery for recurrent astrocytoma, oligodendroglioma, or glioblastoma, will be offered pre-surgical abemaciclib and then resume the drug following recovery from surgery, continuing until disease progression or unacceptable toxicity analogous to the non-surgical patients in cohort A and C. This arm is closed to accrual.

Group III: A:recurrent IDH wildtype RB1 intact grade II and III gliomas Experimental Treatment 1 Intervention

The main study cohort will consist of patients with recurrent IDH wildtype, RB1 wildtype, WHO grade II and III gliomas that have failed previous therapy. This arm is currently on hold.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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]

Abemaciclib has demonstrated promising clinical activity in patients with relapsed mesothelioma that is deficient in the p16ink4A protein, suggesting it may be an effective treatment option for this specific cancer type.

The findings indicate a potential new therapeutic avenue for mesothelioma patients, particularly those whose tumors lack the p16ink4A protein, which is often associated with tumor suppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CDK4/6 Inhibition Shows Clinical Activity in p16ink4A-Deficient Mesothelioma. [2022]

Abemaciclib, a CDK4 and CDK6 inhibitor, shows significantly better brain penetration compared to palbociclib, making it a promising candidate for treating primary brain tumors like glioblastoma.

In preclinical models, abemaciclib not only increased survival in rats with brain tumors but also demonstrated additive effects when combined with the standard treatment temozolomide, suggesting its potential as an effective therapy for brain cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain Exposure of Two Selective Dual CDK4 and CDK6 Inhibitors and the Antitumor Activity of CDK4 and CDK6 Inhibition in Combination with Temozolomide in an Intracranial Glioblastoma Xenograft. Raub, TJ., Wishart, GN., Kulanthaivel, P., et al.[2019]

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]

In phase III clinical trials (MONARCH 2 and MONARCH 3), abemaciclib, a CDK4 & 6 inhibitor, significantly improved progression-free survival and overall survival in women with hormone receptor positive (HR+) and HER2-negative advanced breast cancer when used in combination with endocrine therapy.

Abemaciclib demonstrated a tolerable safety profile, making it a promising treatment option for patients who have progressed after previous endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Development of CDK4 & 6 Inhibitor Abemaciclib in Breast Cancer]. Masuda, N., Saji, S., Kawaguchi, T., et al.[2021]

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]

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

CDK4/6 Inhibition Shows Clinical Activity in p16ink4A-Deficient Mesothelioma. [2022]

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

CDK4/6 inhibition sensitizes intracranial tumors to PD-1 blockade in preclinical models of brain metastasis. [2023]

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

Brain Exposure of Two Selective Dual CDK4 and CDK6 Inhibitors and the Antitumor Activity of CDK4 and CDK6 Inhibition in Combination with Temozolomide in an Intracranial Glioblastoma Xenograft. [2019]

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

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

6. Japan pubmed.ncbi.nlm.nih.gov

[Development of CDK4 & 6 Inhibitor Abemaciclib in Breast Cancer]. [2021]

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

Abemaciclib: First Global Approval. [2019]

8. 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]