Abemaciclib + Darolutamide for Advanced Prostate Cancer

Not currently recruiting at 21 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Eli Lilly and Company

Must be taking: LHRH agonists/antagonists

Must not be taking: CDK4/6 inhibitors, NHAs

Disqualifiers: Heart disease, Chemotherapy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 32 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and tolerability of a new treatment combination: abemaciclib (a CDK4/6 inhibitor) and darolutamide (a hormone therapy) for individuals with advanced prostate cancer that has spread after initial treatment. The focus is on those with metastatic castration-resistant prostate cancer, where cancer grows despite low testosterone levels. Suitable candidates have a confirmed prostate cancer diagnosis and cancer that has spread to bones or soft tissues. Participants must not have received certain previous treatments, such as specific chemotherapy or hormone therapy. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must continue taking luteinizing-hormone-releasing hormone (LHRH) agonists/antagonists if you haven't had a bilateral orchiectomy (surgical removal of both testicles).

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that both abemaciclib and darolutamide have been studied separately for their safety in treating prostate cancer. Abemaciclib has demonstrated effectiveness against metastatic prostate cancer. Studies have found that abemaciclib is generally well-tolerated, though some patients might experience side effects like diarrhea or fatigue.

Darolutamide has also yielded promising results in trials. It has improved patient outcomes when combined with other treatments. Patients taking darolutamide have reported fewer side effects compared to some other treatments, suggesting it may be safer.

Although this trial is in its early stages, the use of these drugs in other studies suggests they are reasonably safe for people with advanced prostate cancer. However, each person can react differently, and ongoing trials will provide more detailed safety information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Abemaciclib and Darolutamide for advanced prostate cancer because it targets cancer cells in a unique way. Unlike traditional treatments like hormone therapy that focus solely on reducing androgen levels, Abemaciclib is a CDK4/6 inhibitor that disrupts the cell cycle, slowing down cancer cell growth. Darolutamide, an androgen receptor inhibitor, works alongside it by blocking the effects of male hormones that can fuel cancer growth. This dual approach not only aims to halt the progression of the disease more effectively but also offers a new hope for patients who may not respond well to existing therapies.

What evidence suggests that this trial's treatments could be effective for advanced prostate cancer?

Research shows that combining the drugs abemaciclib and darolutamide, which participants in this trial will receive, may help treat advanced prostate cancer. Abemaciclib blocks proteins that aid cancer cell growth and has shown positive effects in prostate cancer studies. Darolutamide effectively slows cancer spread and helps men with treatment-resistant prostate cancer live longer. Studies suggest that using these drugs together might enhance their effectiveness against cancer. Although more research is needed, early results are promising for this drug combination in managing prostate cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

Men with prostate cancer that has spread after initial treatment can join this trial. They should be relatively healthy (ECOG PS 0-1), have not had certain prior treatments like CDK4/6 inhibitors or darolutamide, and must continue hormone therapy if they haven't had their testicles removed. No recent severe heart problems allowed.

Inclusion Criteria

My organs are working well.

My prostate cancer was confirmed through a tissue examination.

My prostate cancer has spread, is resistant to hormone therapy, and shows on scans.

Exclusion Criteria

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

I have not had serious heart problems like a heart attack or heart failure in the last 6 months.

I have had treatments like chemotherapy or hormone therapy for advanced prostate cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abemaciclib in combination with darolutamide for prostate cancer

32 months

Monthly visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Darolutamide
• LHRH agonist/antagonist

Trial Overview The study is testing the safety of combining two drugs, Abemaciclib and Darolutamide, in men whose prostate cancer has worsened despite low testosterone levels. Participants will also receive LHRH agonists/antagonists if needed for up to almost three years.

How Is the Trial Designed?

Group I: Abemaciclib + Darolutamide Experimental Treatment 3 Interventions

Abemaciclib plus (+) darolutamide. Participants who have not undergone bilateral orchiectomy are required to continue background androgen deprivation therapy (ADT) with a luteinizing hormone-releasing hormone (LHRH) agonist/antagonist throughout the study.

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?

Eli Lilly and Company

Lead 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

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Published Research Related to This Trial

Darolutamide (NUBEQA™) is a new non-steroidal androgen receptor antagonist approved for treating non-metastatic castration-resistant prostate cancer in men, based on positive results from the phase III ARAMIS trial.

The approval of darolutamide marks a significant milestone in prostate cancer treatment, highlighting its efficacy and safety profile as demonstrated in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide: First Approval. Markham, A., Duggan, S.[2020]

In the phase 3 ARAMIS trial, darolutamide significantly improved metastasis-free survival and overall survival in men with non-metastatic castration-resistant prostate cancer compared to placebo, indicating its efficacy when combined with ongoing androgen deprivation therapy.

Darolutamide was generally well tolerated, showing a low risk of central nervous system-related side effects, which is a common concern with other second-generation androgen receptor inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer. Scott, LJ.[2022]

In a phase 3 trial involving 1509 men with nonmetastatic, castration-resistant prostate cancer, darolutamide significantly improved metastasis-free survival, with a median of 40.4 months compared to 18.4 months for placebo (hazard ratio 0.41).

The safety profile of darolutamide was comparable to placebo, with similar rates of adverse events and no increased risk of serious side effects like seizures or cognitive disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. Fizazi, K., Shore, N., Tammela, TL., et al.[2022]

Darolutamide is an FDA-approved nonsteroidal androgen inhibitor specifically for treating castration-resistant non-metastatic prostate cancer, providing a new option for patients whose PSA levels are rising despite low testosterone.

When used alongside androgen deprivation therapy (ADT), darolutamide, like other newer agents in its class, has been shown to prolong metastasis-free survival and median survival, making it an effective treatment choice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using darolutamide in advanced prostate cancer: How I Do It. Hamilton, J.[2021]

In a study of 137 chemo-naïve patients with metastatic castration-resistant prostate cancer, Enzalutamide (EZ) showed a significantly higher PSA response rate compared to Abiraterone (AA) in the first line of treatment (95.9% vs 67%).

Both AA and EZ had comparable toxicity rates and progression-free survival (PFS) outcomes, indicating that both treatments are effective and well-tolerated options for managing mCRPC without chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. Ferriero, M., Mastroianni, R., De Nunzio, C., et al.[2021]

Darolutamide, a novel nonsteroidal androgen receptor antagonist, has shown a favorable safety profile and significant antitumor activity in early trials for patients with metastatic castration-resistant prostate cancer (CRPC).

Ongoing phase III trials, such as ARAMIS and ARASENS, are evaluating darolutamide's effectiveness in improving metastasis-free survival and overall survival when combined with standard androgen deprivation therapy and docetaxel in men with high-risk nonmetastatic and metastatic hormone-sensitive prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Development of Darolutamide: A Novel Androgen Receptor Antagonist for the Treatment of Prostate Cancer. Fizazi, K., Smith, MR., Tombal, B.[2019]

In a study involving 249 men with metastatic castrate-resistant prostate cancer, patient preference between darolutamide and enzalutamide was balanced, with no significant preference for either treatment (p = 0.92).

Darolutamide was associated with less fatigue and a moderate improvement in episodic memory compared to enzalutamide, suggesting it may offer a better quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Open-label, Cross-over Phase 2 Trial of Darolutamide and Enzalutamide in Men with Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer: Patient Preference and Cognitive Function in ODENZA. Colomba, E., Jonas, SF., Eymard, JC., et al.[2023]

In a phase 2 study involving 60 patients with metastatic castration-resistant prostate cancer (mCRPC), enzalutamide treatment led to a significant decline in prostate-specific antigen (PSA) levels in 45% of patients, indicating its efficacy in managing this advanced cancer.

The study found that the presence of the androgen receptor variant ARV7 was linked to primary resistance to enzalutamide, suggesting that certain androgen signaling characteristics before treatment can predict patient response to the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer. Efstathiou, E., Titus, M., Wen, S., et al.[2022]

In a study of 68 patients with metastatic prostate cancer, both leuprolide and triptorelin effectively reduced plasma testosterone levels, with leuprolide showing a faster decrease at 1 month.

While both treatments were effective in lowering testosterone, there were no significant differences in clinical efficacy or overall safety between the two LHRH analogues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tolerance and clinical and biological responses during the first 6 months of treatment with 1-month sustained release LHRH agonists leuprolerin and triptolerin in patients with metastatic prostate cancer]. Abbou, CC., Lucas, C., Leblanc, V.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05617885

Neo-DAB: Darolutamide and Abemaciclib in Prostate Cancer This research study is trying to determine the safety and efficacy of the combination of two oral drugs, abemaciclib and darolutamide, with androgen ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04408924

Study Details | NCT04408924 | Abemaciclib (LY2835219) ... The study will evaluate how safe and effective abemaciclib is when given to participants whose metastatic prostate cancer progresses after they had received ...

3. withpower.com withpower.com/trial/phase-1-prostatic-neoplasms-2024-1da93

Abemaciclib + Darolutamide for Advanced Prostate Cancer Darolutamide has shown effectiveness in delaying metastasis and death in men with nonmetastatic, castration-resistant prostate cancer, and has demonstrated ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1470204525004759

Abemaciclib plus abiraterone in patients with metastatic ... Abemaciclib, a potent CDK4 and CDK6 inhibitor, has shown antitumour activity in prostate cancer models and in patients with metastatic castration-resistant ...

5. bayer2019tf.q4web.com bayer2019tf.q4web.com/news/news-details/2025/New-Data-for-NUBEQA-Build-on-Safety-and-Efficacy-Results-Across-Subgroups-of-Patients-with-Metastatic-Hormone-Sensitive-Prostate-Cancer/default.aspx

New Data for NUBEQA® Build on Safety and Efficacy Results ... New subgroup data from the investigational Phase III ARANOTE trial show NUBEQA (darolutamide) plus androgen-deprivation therapy (ADT) improved radiological ...