Abemaciclib + MK-6482 for Renal Cell Carcinoma

No longer recruiting at 1 trial location

Overseen By Toni K Choueiri, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: CDK4/6 inhibitors, HIF-2α inhibitors

Disqualifiers: Investigational agents, HIV, Hepatitis, 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: 8

Duration: 12-18 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether two drugs, abemaciclib (a cancer treatment) and MK-6482 (an experimental treatment), can safely and effectively slow the growth of clear cell renal cell carcinoma (ccRCC), a type of kidney cancer. Researchers aim to evaluate abemaciclib both alone and in combination with MK-6482. Suitable candidates for this trial have advanced kidney cancer that has not responded to previous treatments, including one anti-VEGFR therapy and one immune checkpoint inhibitor. Participants must have clear cell features in their cancer and be able to swallow pills. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking any investigational agents, CDK4/6 inhibitors, and certain small molecule therapeutics before starting the study drugs. You also need to stop biologic therapy at least 28 days before starting the trial. If you're taking herbal medications or certain fruits, you must stop them 7 days before starting the study drugs.

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

Research shows that abemaciclib, when used alone, is generally safe but can cause some side effects. In a previous study, most patients (91%) experienced treatment-related side effects, but none were very severe. Although abemaciclib did not effectively treat kidney cancer on its own, it did not introduce any new safety issues.

MK-6482 has shown promise in treating certain kidney tumors, particularly those associated with von Hippel-Lindau disease. This suggests potential effectiveness and safety for other types of kidney cancer, though specific safety details for MK-6482 alone in kidney cancer are not provided here.

The combination of abemaciclib and MK-6482 might be safe for slowing kidney cancer growth. However, detailed safety information for the combination is still being collected, and further research is needed to confirm these early findings. This trial is in its early stages, so safety data is still being gathered, but no major concerns have been reported so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Abemaciclib and MK-6482 for renal cell carcinoma because these treatments offer a fresh approach to tackling cancer. Unlike traditional therapies that mainly focus on inhibiting vascular endothelial growth factor (VEGF), Abemaciclib targets cyclin-dependent kinases 4 and 6 (CDK4/6), which are crucial for cell division and tumor growth. Meanwhile, MK-6482 acts on hypoxia-inducible factor 2-alpha (HIF-2α), a different pathway involved in cancer progression. This combination could potentially provide a more comprehensive attack on cancer cells by hitting them from multiple angles, offering hope for improved outcomes in renal cell carcinoma.

What evidence suggests that this trial's treatments could be effective for renal cell carcinoma?

In this trial, participants will join different treatment arms to evaluate the effectiveness of abemaciclib alone and in combination with MK-6482. Studies have shown that abemaciclib alone is not very effective for treating advanced kidney cancer, with patients' cancer not worsening for about 1.8 months and an average survival of about 9.1 months. In Arm 1, participants will receive abemaciclib alone. Arm 2 will explore the combination of abemaciclib with MK-6482, which has shown promise in treating kidney cancer. Specifically, 24% of patients experienced tumor shrinkage, and 56% had stable disease. This combination could potentially slow cancer growth more effectively than abemaciclib alone. ^{2 3 4 5 6}

Who Is on the Research Team?

Toni Choueiri, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic renal cell carcinoma that has a clear cell component. Participants must have previously tried and not responded well to at least one anti-VEGFR therapy and an immune checkpoint inhibitor. They should be in relatively good health, able to take oral medication, and willing to use contraception.

Inclusion Criteria

You need to have at least 100,000 platelets per microliter of blood.

You have a disease that can be measured using a specific medical guideline.

My organ and bone marrow functions are normal.

Exclusion Criteria

I have previously been treated with a HIF-2α inhibitor.

Participants who have taken herbal medications and certain fruits within 7 days prior to starting study drug

I am willing and able to follow the study rules.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abemaciclib alone or in combination with MK-6482 for 12 to 18 months

12-18 months

Imaging assessments every 8 weeks during the first six months, then every 12 weeks

Safety Follow-up

Participants undergo safety follow-up visits after completing treatment

3 months

Long-term Follow-up

Participants are monitored for overall survival and health status every 6 months

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• MK-6482

Trial Overview

The study is testing the safety and effectiveness of two drugs, Abemaciclib alone or combined with MK-6482, in slowing down the growth of clear cell renal cell carcinoma (ccRCC). It will involve patients who meet specific health criteria.

How Is the Trial Designed?

Group I: Abemaciclib-Arm 1 Experimental Treatment 1 Intervention

Arm 1 * Abemaciclib will be taken at a standard recommended starting dose 2X daily during 28 day study cycles and will be taken until radiographic progression, unacceptable toxicity or withdrawal. * Imaging assessments will be performed every 8 weeks during the first six months of the study, then every 12 weeks, in both Arm 1 and Arm 2.

Group II: Abemaciclib and MK-6482-Arm 2 Experimental Treatment 2 Interventions

Arm 2 * Arm 2 will start enrolling only after there is experience with Arm 1 to see what abemaciclib effects are when given alone, * Dose escalation will occur following a 3+3 design. * Abemaciclib will be taken 2X daily uring 28 day study cycle * MK-6482 will be taken 1x daily during 28 day study cycle * Imaging assessments will be performed every 8 weeks during the first six months of the study, then every 12 weeks, in both arms.

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?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9807446/

Real‐world data for the renal safety of abemaciclib ...

This study shows that abemaciclib combined with bisphosphonate would be safe for renal function in HR+/HER2− ABC patients with bone metastases.

2.

cancernetwork.com

cancernetwork.com/view/abemaciclib-may-show-synergistic-effect-in-kidney-cancer-combination-trials

Abemaciclib May Show Synergistic Effect in Kidney Cancer ...

The median progression-free survival (PFS) was 1.8 months (95% CI, 1.5-1.9), and the median overall survival (OS) was 9.1 months (95% CI, 2.1- ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04627064

NCT04627064 | ABEMA Alone or in COMBO With MK-6482

This research study will assess whether abemaciclib alone or in combination with MK-6482 are safe and effective in slowing down the growth of clear cell ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12011124/

Abemaciclib-associated kidney injuries: A retrospective ...

We selected 10,757 matched reports associated with abemaciclib, among which we found eight adverse reactions about kidney injuries correlated ...

5.

onclive.com

onclive.com/view/abemaciclib-monotherapy-does-not-elicit-responses-in-advanced-renal-cell-carcinoma

Abemaciclib Monotherapy Does Not Elicit Responses in ...

The median progression-free survival (PFS) was only 1.8 months (95% CI, 1.5-1.9) and the median overall survival (OS) was 9.1 months (95% CI, ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40081120/

CDK4/6 Inhibition With Abemaciclib in Patients ...

In patients with heavily pretreated metastatic RCC, abemaciclib monotherapy had no clinically meaningful activity without new toxicity signals. This data ...