Abemaciclib + Fulvestrant for Endometrial Cancer

Not currently recruiting at 7 trial locations

Overseen By Vicky Makker, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Fulvestrant, Everolimus, mTor inhibitors, others

Disqualifiers: Visceral crisis, Liver disease, 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

Compensation: Varies

Number of Visits: 1

Duration: Until disease progression or intolerable toxicity

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a combination of two medications, abemaciclib (a cancer treatment drug) and fulvestrant, can effectively treat endometrial cancer and identify potential side effects. The focus is on patients whose cancer has returned or has not responded to other treatments. The trial seeks participants with hormone receptor-positive endometrial cancer that has not improved with standard treatments. Participants will receive these medications regularly and will be monitored for changes in their condition. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that any hormonal therapy directed at the malignant tumor must be stopped at least 2 weeks before starting the study treatment. Additionally, any prior therapy for the tumor, including immunologic agents and radiotherapy, must be discontinued before the first study treatment. A washout period (time without taking certain medications) of at least 21 days is required after the last chemotherapy dose and 14 days after radiotherapy.

Is there any evidence suggesting that the combination of abemaciclib and fulvestrant is likely to be safe for humans?

Research has shown that the combination of abemaciclib and fulvestrant has been tested for safety. In one study, the most common serious side effects included a low white blood cell count in 26% of patients and a low red blood cell count in 19% of patients. This treatment revealed no new safety concerns.

Another report indicates that the side effects of this treatment pair are similar to those of other drugs in its group, known as CDK4/6 inhibitors. While side effects are expected, they can be managed. It is important to consult a healthcare professional about what these side effects might mean. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Abemaciclib combined with Fulvestrant for endometrial cancer because this treatment offers a novel approach by targeting specific molecules involved in cancer cell growth. Unlike traditional chemotherapy, which attacks all rapidly dividing cells, Abemaciclib specifically inhibits proteins called CDK4 and CDK6 that are crucial for cancer cell division. Fulvestrant complements this action by degrading estrogen receptors, which many endometrial cancer cells depend on for growth. This targeted strategy not only aims to be more effective against the cancer but also potentially reduces the side effects associated with conventional treatments.

What evidence suggests that the combination of abemaciclib and fulvestrant could be effective for endometrial cancer?

Research has shown that using abemaciclib with fulvestrant is promising for treating certain cancers. In this trial, participants will receive this combination treatment. Studies have found that this combination can prevent cancer from worsening for about 9 months on average. Additionally, 44% of patients responded well, with their tumors either shrinking or remaining stable. This treatment targets specific parts of cancer cells to inhibit their growth. Overall, these findings suggest that this treatment could be effective for endometrial cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Angela Green, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for women over 18 with recurrent endometrial cancer who've had a hysterectomy and/or oophorectomy, are postmenopausal, and may have had limited prior treatments. They should be in good health otherwise, not pregnant or breastfeeding, willing to use contraception if of childbearing potential, and able to swallow pills.

Inclusion Criteria

I have had both of my ovaries surgically removed.

Agreement to pre- and post-treatment tumor biopsies

Disease that is measurable as per RECIST v1.1

Exclusion Criteria

I have been treated with specific cancer drugs like fulvestrant or CDK4/6 inhibitors.

Serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study

I am HIV positive.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Abemaciclib 150 mg orally every 12 hours and Fulvestrant 500 mg intramuscularly according to the specified schedule

Until disease progression or intolerable toxicity

Visits on days 1 and 15 during cycle 1, then day 1 of each subsequent 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Fulvestrant

Trial Overview The study tests the effectiveness of combining two drugs: Abemaciclib and Fulvestrant in treating recurrent endometrial cancer. It also examines the side effects of this treatment combination on participants.

How Is the Trial Designed?

Group I: Fulvestrant in Combination with Abemaciclib Experimental Treatment 2 Interventions

Eligible patients will take Abemaciclib 150 milligrams mg orally once every 12 hours on days 1-28. Fulvestrant will be dosed 500mg intramuscularly (IM) on days 1 and 15 during cycle 1 and then on Day 1 during subsequent cycles. Each cycle will be 28 days in duration. Patients will receive study treatment until disease progression, intolerable toxicity, elective withdrawal from the study, or study termination.

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

Published Research Related to This Trial

In the MONARCH 2 study involving 669 women with advanced breast cancer, the combination of abemaciclib and fulvestrant significantly improved progression-free survival (PFS) to a median of 16.4 months compared to 9.3 months with fulvestrant alone.

The combination therapy also achieved a higher objective response rate (ORR) of 48.1% versus 21.3% in the control group, while maintaining a tolerable safety profile, with common side effects including diarrhea and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2- Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy. Sledge, GW., Toi, M., Neven, P., et al.[2022]

In a phase II study involving 30 patients with recurrent ER-positive endometrial cancer, the combination of letrozole and abemaciclib showed a 30% objective response rate, indicating promising efficacy in treating this type of cancer.

The treatment resulted in a median progression-free survival of 9.1 months, with 55.6% of patients remaining progression-free at 6 months, while the most common serious side effects were neutropenia and anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II, Two-Stage Study of Letrozole and Abemaciclib in Estrogen Receptor-Positive Recurrent Endometrial Cancer. Konstantinopoulos, PA., Lee, EK., Xiong, N., et al.[2023]

In the premenopausal subgroup of the MONARCH 2 trial, patients treated with abemaciclib plus fulvestrant experienced significantly improved median progression-free survival (PFS) of 28.6 months compared to 10.26 months for those receiving placebo plus fulvestrant, indicating strong efficacy in hormone receptor-positive, HER2-negative advanced breast cancer.

The safety profile of abemaciclib plus fulvestrant was consistent with previous findings, supporting its use as an effective treatment option for premenopausal patients who are resistant to endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib plus fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in premenopausal women: subgroup analysis from the MONARCH 2 trial. Neven, P., Rugo, HS., Tolaney, SM., et al.[2021]

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 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]

In a pooled analysis of 1152 patients from the MONARCH 2 and MONARCH 3 studies, abemaciclib combined with endocrine therapy showed a consistent improvement in progression-free survival (PFS) across all age groups, indicating its efficacy in treating HR+, HER2- advanced breast cancer regardless of age.

Older patients experienced higher rates of clinically relevant side effects, such as diarrhea and nausea, but these were manageable with dose adjustments, suggesting that while safety concerns exist, the treatment remains effective for older populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of abemaciclib plus endocrine therapy in older patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: an age-specific subgroup analysis of MONARCH 2 and 3 trials. Goetz, MP., Okera, M., Wildiers, H., et al.[2022]

In a phase III study involving 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer, abemaciclib significantly improved progression-free survival compared to placebo, with a hazard ratio of 0.54, indicating a strong efficacy as initial therapy.

The most common side effect of abemaciclib was diarrhea, occurring in 81.3% of patients, but most cases were mild (grade 1), suggesting that while there are some adverse effects, the treatment has a tolerable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. Goetz, MP., Toi, M., Campone, M., et al.[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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39561275/

A Phase II Study of Fulvestrant plus Abemaciclib in Hormone ... The median duration of response was 15.6 months. The median progression-free survival was 9.0 months (90% confidence interval, 1.8-20.4). The ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.5511

A phase II study of fulvestrant and abemaciclib in hormone ... 24 pts (89%) had tumors with endometrioid histology. 9 pts (33%) had prior hormonal therapy and 26 pts (96%) had ≥1 prior line of chemotherapy.

3. aacrjournals.org aacrjournals.org/clincancerres/article/31/11/2088/762529/A-Phase-II-Study-of-Fulvestrant-plus-Abemaciclib

A Phase II Study of Fulvestrant plus Abemaciclib in Hormone ... In the present study, abemaciclib and fulvestrant demonstrated an ORR of 44% and a median PFS of 9.0 months, further supporting the promising activity of CDK4/6 ...

4. cancernetwork.com cancernetwork.com/view/abemaciclib-plus-hormonal-therapy-shows-promising-efficacy-in-lgsoc-eec

Abemaciclib Plus Hormonal Therapy Shows Promising ... Abemaciclib (Verzenio) plus hormonal therapy demonstrated clinical activity in patients with recurrent low-grade serous ovarian cancer (LGSOC) and endometrioid ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11431580/

Therapeutic Prospects of Abemaciclib for Patients with ... The efficacy of abemaciclib, a CDK4/6 inhibitor, has been proven, and abemaciclib was well tolerated in breast cancer and endometroid ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2017/208716Orig1s000RiskR.pdf

208716Orig1s000 - accessdata.fda.gov 5 Risk Assessment & Safe-Use Conditions. The safety profile of abemaciclib for the proposed indications is based on safety data from the Phase 3.