Abemaciclib + Letrozole for Endometrial Cancer

Not currently recruiting at 31 trial locations

Overseen By Jennifer Klein, MEd

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Gynecologic Oncology Group

Must not be taking: CDK4/6 inhibitors, Hormonal therapy, Steroids, Immunosuppressants

Disqualifiers: Other malignancies, Cardiac disease, Active infections, 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: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two medications, abemaciclib (a CDK4/6 inhibitor) and letrozole (an aromatase inhibitor), to determine if they can halt the progression of endometrial cancer. It targets individuals with advanced, persistent, or recurrent endometrial cancer that surgery or radiation cannot cure. This trial may suit those with measurable endometrial cancer who can swallow pills. Participants will take the medications until the cancer progresses or they experience unacceptable side effects. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) of at least 21 days after the last dose of any previous systemic therapy before starting the trial treatment. If you are on systemic steroids or immunosuppressive agents, you may need to stop them, as they are not allowed during the trial.

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

Research has shown that abemaciclib and letrozole are generally safe and well-tolerated by patients. Some studies have combined these drugs with metformin and found them safe for treating recurring estrogen receptor-positive endometrial cancer. Reports indicate that these medications remain safe even when used with other drugs, without causing serious side effects.

These findings suggest that abemaciclib and letrozole have a good safety record. While mild side effects may occur, they are usually easy to manage. However, this trial is still in its early stages, so researchers are still collecting safety information. Participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of abemaciclib and letrozole for endometrial cancer because it offers a novel approach compared to standard treatments like chemotherapy or hormonal therapy alone. Abemaciclib is a CDK4/6 inhibitor, which means it targets specific proteins involved in cell division, potentially stopping cancer cells from growing and dividing. When combined with letrozole, an aromatase inhibitor that reduces estrogen production, this treatment may more effectively halt cancer progression. This dual mechanism could provide a more targeted and less toxic option for patients, compared to traditional therapies.

What evidence suggests that this treatment might be an effective treatment for endometrial cancer?

Research has shown that combining abemaciclib and letrozole can help treat certain types of endometrial cancer. In one study, about 32% of patients experienced a significant reduction in tumor size, meaning the tumors either disappeared completely or became smaller. Another study found this combination particularly promising for treating recurrent ER-positive endometrial cancer, a type that relies on hormones to grow. Abemaciclib stops cancer cells from growing, while letrozole reduces hormone levels, slowing the cancer's progression. ^{2 5 6 7 8}

Who Is on the Research Team?

Marilyn Huang, MD

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

This trial is for adults with advanced, persistent, or recurrent endometrioid endometrial cancer that can't be cured by surgery or radiotherapy. Participants must have measurable disease, no more than two prior systemic therapies (only one may include chemo), and good organ function. They cannot join if they've had CDK4/6 inhibitors before, other cancer types like clear cell or serous cancers, known allergies to the drugs being tested, active infections, CNS metastases, HIV infection, certain medical conditions affecting drug absorption or bleeding risk.

Inclusion Criteria

I've had chemotherapy for early-stage cancer or for a pelvic recurrence.

My cancer's MMR, MSI, and hormone receptor status have been tested and reported if available.

My cancer is endometrioid type, confirmed by surgery or biopsy.

Exclusion Criteria

I have taken medication that targets CDK4/6 for my cancer.

My cancer has spread to my brain.

I do not have any ongoing serious infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abemaciclib and letrozole until unacceptable toxicity, disease progression, or withdrawal

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Letrozole

Trial Overview The trial tests how well patients with specific endometrial cancer respond to a combination of Abemaciclib and Letrozole after six months without their disease getting worse. It's a phase II study where all participants receive the same treatment until it's not tolerated anymore or until the disease progresses.

How Is the Trial Designed?

Group I: Abemaciclib and Letrozole Experimental Treatment 2 Interventions

Study treatment will consist of abemaciclib 150mg orally twice a day and letrozole 2.5mg orally once a day.

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?

Gynecologic Oncology Group

Lead Sponsor

Trials

251

Recruited

65,400+

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 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 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 a study of 10 post-menopausal patients with endometrial cancer, short-term treatment with letrozole was well-tolerated and led to a significant 37.8% reduction in blood estradiol levels, indicating its effectiveness in lowering estrogen levels.

The treatment also resulted in notable clinical improvements, such as pain relief and a 31.1% decrease in endometrial ultrasound signal, suggesting potential benefits in managing endometrial cancer before surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant therapy of endometrial cancer with the aromatase inhibitor letrozole: endocrine and clinical effects. Berstein, L., Maximov, S., Gershfeld, E., 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 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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.5513

Phase 2 study of letrozole, abemaciclib, and metformin in ... Eight pts exhibited OR: 3 complete responses (CRs) and 5 partial responses (PRs),ORR 32% (95% CI 14.9% to 53.5%). Sixteen (64%) pts had stable ...

2. dana-farber.org dana-farber.org/newsroom/news-releases/2022/drug-combination-shows-effectiveness-in-patients-with-recurrent-er-positive-endometrial-cancer

Drug combination shows effectiveness in patients with ... “Based on our findings, the letrozole/abemaciclib combination should be considered worthy of further evaluation for patients with recurrent ER- ...

3. onclive.com onclive.com/view/metformin-plus-letrozole-and-abemaciclib-induces-crs-in-er-recurrent-endometrial-cancer

Metformin Plus Letrozole and Abemaciclib Induces CRs in ... Findings from the study showed that patients who received the combination (n = 25) achieved an overall response rate (ORR) of 32%, including a ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03675893

Study Details | NCT03675893 | RESOLVE: Abemaciclib + ... Abemaciclib is a cyclin-dependent kinase (CDK) inhibitor. CDK inhibitors work to stop cancer cell growth. Letrozole is a hormonal therapy that works by lowering ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10982620/

A phase II, multicenter, open-label study of abemaciclib and ... The combination therapy of abemaciclib and letrozole will provide a clinically meaningful therapeutic benefit, with an overall response rate of >25%.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04393285

Abemaciclib and Letrozole to Treat Endometrial Cancer This is a phase II single arm trial to determine the percentage of patients without evidence of disease progression on abemaciclib and letrozole in advanced ...

7. physicianresources.dana-farber.org physicianresources.dana-farber.org/news/treatment-of-recurrent-endometrial-cancer-with-metformin-letrozole-and-abemaciclib-is-safe-and-promising-dana-farber-research-shows

Treatment of Recurrent Endometrial Cancer with Metformin ... Treatment with metformin, letrozole, and abemaciclib for recurrent estrogen receptor-positive endometrial cancer is safe and appears to induce deeper and more ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10901901/

Combined aromatase, CDK4/6 and PI3K blockade using ... We evaluated the combination of abemaciclib, letrozole and LY3023414 (an orally available, selective inhibitor of the class I PI3K isoforms and mTORC1/2) in ...