Abemaciclib for Endometrial cancer (cancer of the lining of the uterus)
Dana-Farber Cancer Institute· RESOLVE
Reviewed by Blane Jackson, DDS, MBA. Educational analysis only. Read the editorial policy and disclosures.
NCT03675893 on ClinicalTrials.gov →Study type
interventional
Design
Non-randomized, sequential, op…
Target enrollment
110
Est. completion
2028-08-01
Investor scorecard
Probability of success
moderate
Timeline to catalyst
Interim data may be available as early as 2024-2025, but final results are expected around 2028. Investors should watch for presentations at major conferences like ASCO or ESGO.
Potential stock impact
SignificantThe trial is a phase 2 with multiple arms, which increases the chance of finding some signal. However, endometrial cancer is a heterogeneous disease, and prior CDK4/6 inhibitor trials have shown mixed results. The addition of metformin or gedatolisib may improve efficacy, but also adds toxicity. The trial is not randomized, which can lead to bias. Given the early stage and long timeline, the probability of eventual approval is moderate, perhaps 30-40%.
What is being tested?
This trial tests a combination of drugs for endometrial cancer, a cancer that starts in the lining of the uterus. The main drug is abemaciclib, which is a type of targeted therapy called a CDK4/6 inhibitor. It works by blocking certain proteins that help cancer cells divide. The trial also tests adding other drugs: letrozole (a hormone therapy that lowers estrogen), metformin (a diabetes drug that may have anti-cancer effects), and gedatolisib (a drug that blocks a growth pathway in cells). The goal is to see if these combinations are safe and effective in patients whose cancer has spread or come back.
How does the trial work?
Patients are enrolled into different groups (cohorts) sequentially. Each group receives a different combination: some get letrozole plus abemaciclib, others get that plus metformin, and others get that plus gedatolisib. The trial is not randomized, meaning patients are assigned to a group based on when they join. They receive treatment in cycles, typically with pills taken daily. Regular check-ups include imaging scans and blood tests to monitor tumor size and side effects. The trial aims to enroll 110 patients across multiple sites. Treatment continues until the cancer progresses or side effects become unacceptable.
What does success look like?
Success would be shown if the treatment improves progression-free survival (how long patients live without cancer growing) or causes tumors to shrink. For endometrial cancer, a meaningful response rate might be around 20-30% in this setting, and progression-free survival might be extended by several months compared to historical data. The trial will also look at overall survival and side effects. If the results are promising, it could lead to a larger phase 3 trial.
What it means for investors
For investors, this trial is important because it tests a novel combination that could address a significant unmet need in endometrial cancer, especially for patients with hormone receptor-positive disease. If the trial succeeds, it could expand the use of abemaciclib, which is already approved for breast cancer, into a new indication. This could boost sales for Eli Lilly, the maker of abemaciclib. However, the trial is early-stage and has a long timeline (expected completion in 2028). Investors should watch for interim data releases, which could cause stock volatility. If the trial fails, it would be a setback for Lilly's pipeline in this area, but given the multiple arms, there might be some positive signals even if not all arms succeed.
Trial endpoints
Primary endpoints
Secondary endpoints
Competitive landscape
Endometrial cancer is the most common gynecologic malignancy in the US, with an estimated 65,950 new cases and 12,550 deaths in 2022. The market for treatments is growing, especially for advanced or recurrent disease. Current options include chemotherapy, hormonal therapy, and immunotherapy. The global endometrial cancer treatment market was valued at around $4 billion in 2020 and is projected to grow. A successful combination therapy could capture a significant share, especially if it offers better efficacy than existing options.
| Drug | Sponsor | Phase | Differentiation |
|---|---|---|---|
| Lenvatinib + Pembrolizumab | Eisai/Merck | Phase 1 | Approved for advanced endometrial cancer that is not MSI-H or dMMR, after prior therapy. It combines a multi-kinase inhibitor with an immunotherapy. |
| Dostarlimab | GSK | Phase 1 | An anti-PD-1 immunotherapy approved for dMMR recurrent or advanced endometrial cancer. |
| Mirvetuximab soravtansine | ImmunoGen | Phase 1 | An antibody-drug conjugate targeting FRα, being tested in endometrial cancer, though more advanced in ovarian cancer. |
Historical context
Prior trial results
Abemaciclib has been studied in breast cancer, where it is approved. In endometrial cancer, earlier phase 1/2 studies have shown activity when combined with letrozole, with response rates around 30% in hormone receptor-positive disease. Metformin has been studied in various cancers with mixed results. Gedatolisib is an investigational PI3K/mTOR inhibitor that has shown promise in early trials.
Regulatory history
Abemaciclib is approved for HR+/HER2- breast cancer. It has not received any special designations for endometrial cancer. Letrozole is approved for breast cancer. Metformin is approved for diabetes. Gedatolisib is investigational.
Similar drug precedents
CDK4/6 inhibitors like palbociclib and ribociclib have been tested in endometrial cancer with modest activity. Hormonal therapy with aromatase inhibitors is a standard treatment for hormone receptor-positive endometrial cancer, but responses are often short-lived. Combining CDK4/6 inhibitors with hormonal therapy has been successful in breast cancer, providing a rationale for this approach in endometrial cancer.