Abemaciclib + Cabozantinib for Kidney Cancer

Recruiting at 7 trial locations

Overseen By Robert Motzer, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: CYP3A4 inducers/inhibitors, Anticoagulants

Disqualifiers: Brain metastasis, Cardiovascular events, 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

43 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a combination of the drugs abemaciclib and cabozantinib is safe and effective for treating two types of advanced kidney cancer: metastatic clear cell renal cell carcinoma (ccRCC) and translocation-associated renal cell cancer (tRCC). Researchers will test different doses to identify the highest ones that cause only mild or few side effects. This trial may suit individuals with advanced kidney cancer that has worsened after at least two other treatments, including one targeting specific proteins (PD-1 or PD-L1) and another aimed at blood vessel growth (VEGFR therapy). As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot take certain medications like moderate or strong CYP3A4 inducers or inhibitors, and some anticoagulants. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Research has shown that cabozantinib effectively treats advanced kidney cancer. The METEOR study demonstrated that it helps patients live longer and respond better to treatment, indicating it is generally well-tolerated. Conversely, abemaciclib, tested as a single treatment for kidney cancer, did not show any unexpected side effects.

This study is in an early phase, so researchers are closely monitoring its safety. They are testing different doses to find the safest one with the fewest side effects. The goal is to ensure the combination of abemaciclib and cabozantinib is safe before progressing to larger trials. For those considering joining a trial, this phase ensures the treatment undergoes careful safety evaluation. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for kidney cancer?

Researchers are excited about the combination of Abemaciclib and Cabozantinib for treating kidney cancer because these drugs target cancer in a unique way compared to standard treatments. Abemaciclib is a CDK4/6 inhibitor, which disrupts the cancer cell cycle, while Cabozantinib inhibits multiple pathways involved in tumor growth and spread, including MET, VEGFR, and AXL. This dual approach could potentially overcome resistance to current therapies like VEGF inhibitors or mTOR inhibitors, offering hope for patients whose cancers have progressed despite these treatments.

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

Studies have shown that cabozantinib holds promise in treating advanced kidney cancer, specifically clear cell renal cell carcinoma (ccRCC). In previous research, 28% of patients experienced tumor shrinkage, known as a partial response. Abemaciclib, another drug, stops cancer cells from growing and dividing. In this trial, participants will receive a combination of abemaciclib and cabozantinib, potentially enhancing effectiveness by attacking the cancer in different ways. This combination aims to improve the chances of slowing or stopping the cancer's growth. ^{1 2 3 5 6}

Who Is on the Research Team?

Martin Voss, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with metastatic clear cell renal cell carcinoma (ccRCC), a type of kidney cancer. Participants should not have had previous treatments that failed and must be in good physical condition to handle the study drugs.

Inclusion Criteria

Signed and dated IRB-approved Informed Consent Form

Patient must be able to provide informed consent, or a legal authorized representative (LAR) must be identified to provide consent in cases where the patient cannot

I have been diagnosed with stage IV clear cell kidney cancer.

Exclusion Criteria

I have been treated with abemaciclib or cabozantinib before.

My blood pressure is not controlled by medication.

Previously identified allergy or hypersensitivity to components of the study treatment formulations

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of abemaciclib and cabozantinib to determine the maximally tolerated dose

Up to 1 year

Dose Expansion

Participants receive the determined dose of abemaciclib and cabozantinib to evaluate safety and effectiveness

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib and Cabozantinib

Trial Overview The study is testing the combination of two drugs, Abemaciclib and Cabozantinib, to see if they're safe and effective for treating ccRCC. Researchers will try different doses to find the most effective one with the least side effects.

How Is the Trial Designed?

Group I: Abemaciclib and Cabozantinib Experimental Treatment 2 Interventions

This is a two-site single-arm open-label phase 1b/2 clinical trial evaluating abemaciclib plus cabozantinib in patients with metastatic ccRCC and tRCC that have progressed on therapy. The study comprises a dose escalation portion followed by a dose expansion phase 2 trial.

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

Exelixis

Industry Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

Published Research Related to This Trial

In a phase 3 trial involving 658 patients with metastatic renal-cell carcinoma, cabozantinib significantly improved progression-free survival (7.4 months) compared to everolimus (3.8 months), indicating its greater efficacy after VEGFR-targeted therapy.

Cabozantinib also showed a higher objective response rate (21% vs. 5% for everolimus) and a lower risk of progression or death (42% reduction), although both treatments had similar rates of treatment discontinuation due to adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. Choueiri, TK., Escudier, B., Powles, T., et al.[2022]

Cabozantinib was designated as a breakthrough drug by the FDA and approved in 2016 for treating advanced clear cell renal cell carcinoma (ccRCC), which is the most common kidney cancer type, accounting for about 90% of cases.

The METEOR trial demonstrated significant efficacy for cabozantinib in advanced RCC, and ongoing studies like the CABOSUN trial will further clarify its effectiveness compared to other treatments like sunitinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical use of cabozantinib in the treatment of advanced kidney cancer: efficacy, safety, and patient selection. Yu, SS., Quinn, DI., Dorff, TB.[2022]

In the phase 3 METEOR trial, cabozantinib significantly improved progression-free survival (PFS), objective response rate (ORR), and overall survival (OS) compared to everolimus in patients with advanced renal cell carcinoma (RCC) who had previously undergone antiangiogenic therapy.

Specifically, cabozantinib showed a median PFS of 9.1 months versus 3.7 months for everolimus in patients previously treated with sunitinib, and even better results were observed in those treated with anti-PD-1/PD-L1 therapy, indicating its efficacy across different treatment backgrounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes based on prior therapy in the phase 3 METEOR trial of cabozantinib versus everolimus in advanced renal cell carcinoma. Powles, T., Motzer, RJ., Escudier, B., et al.[2021]

Cabozantinib (CAB) has shown significant improvements in overall survival and progression-free survival in phase-III studies for patients with advanced renal cell carcinoma and hepatocellular carcinoma, leading to its approval in Japan for these conditions.

CAB may enhance antitumor immunity and, when combined with PD-1 checkpoint inhibitors like nivolumab, has demonstrated increased progression-free survival compared to standard treatments, indicating a potential synergistic effect in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological properties and clinical outcomes of the anti-cancer drug, cabozantinib (CABOMETYX®)]. Osaka, T., Yamaguchi, N., Hara, T.[2022]

The combination of cabozantinib (a tyrosine kinase inhibitor) and nivolumab (an immune checkpoint inhibitor) significantly improved progression-free survival, overall survival, and objective response rates in patients with untreated advanced renal cell carcinoma compared to sunitinib, supporting its approval as a first-line therapy.

While the safety profile of the combination treatment is generally manageable, it requires careful monitoring and management of overlapping adverse events, such as diarrhea and hepatotoxicity, to maintain patient tolerability and treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of adverse events associated with cabozantinib plus nivolumab in renal cell carcinoma: A review. McGregor, B., Mortazavi, A., Cordes, L., et al.[2023]

In a real-world analysis of adverse events from two combination therapies for advanced renal cell carcinoma, cabozantinib (CAB) plus nivolumab (NIVO) showed higher incidence rates of seven types of toxicities compared to ipilimumab (IPI) plus NIVO.

Conversely, IPI + NIVO was associated with higher rates of three types of toxicities and had a greater incidence of serious adverse events, suggesting that both therapies have distinct safety profiles that can guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. Blas, L., Shiota, M., Tsukahara, S., et al.[2023]

Cabozantinib has shown significant efficacy in treating advanced kidney cancer, with a 28% objective response rate and a median progression-free survival of 14.7 months based on a phase II trial involving patients with renal cancer.

The drug also demonstrated notable effectiveness in managing bone metastases, which is crucial for improving quality of life in patients, and further studies are planned to compare its effectiveness against standard VEGF inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib as a novel therapy for renal cell carcinoma. Vaishampayan, U.[2022]

In a phase II trial involving 47 patients with advanced non-clear-cell renal cell carcinoma, the combination of cabozantinib and nivolumab showed a promising objective response rate of 47.5% in patients with papillary, unclassified, or translocation-associated RCC, along with a median progression-free survival of 12.5 months.

The treatment was less effective in chromophobe RCC, with no objective responses observed, highlighting the need for further research into genomic predictors of response, particularly mutations like NF2 and FH that were associated with better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non-Clear-Cell Renal Cell Carcinoma and Genomic Correlates. Lee, CH., Voss, MH., Carlo, MI., et al.[2023]

In a phase 3 trial involving 651 patients with untreated advanced renal-cell carcinoma, the combination of nivolumab and cabozantinib significantly improved progression-free survival (16.6 months) compared to sunitinib (8.3 months), with a hazard ratio of 0.51, indicating a 49% reduction in the risk of disease progression or death.

Patients receiving nivolumab plus cabozantinib also had a higher overall survival rate at 12 months (85.7%) compared to those on sunitinib (75.6%), and a greater objective response rate (55.7% vs. 27.1%), although adverse events were common in both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. Choueiri, TK., Powles, T., Burotto, M., et al.[2022]

In a phase 3 trial involving 855 patients with untreated advanced renal-cell carcinoma, the combination of cabozantinib with nivolumab and ipilimumab significantly improved progression-free survival compared to nivolumab and ipilimumab alone, with a 12-month progression-free survival rate of 57% versus 49%.

However, the experimental group experienced a higher incidence of severe adverse events (grade 3 or 4) at 79%, compared to 56% in the control group, indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. Choueiri, TK., Powles, T., Albiges, L., et al.[2023]

Cabozantinib shows promising anti-tumor activity in patients with metastatic clear cell renal cell carcinoma (RCC), with a partial response observed in 28% of the 25 heavily pretreated participants.

The treatment demonstrated a median progression-free survival of 12.9 months and a median overall survival of 15.0 months, with a safety profile consistent with other similar therapies, indicating its potential as a viable option for advanced RCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of cabozantinib (XL184) in patients with renal cell cancer. Choueiri, TK., Pal, SK., McDermott, DF., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06835972

NCT06835972 | A Study of Abemaciclib and Cabozantinib ... The researchers are doing this study to find out whether the combination of abemaciclib and cabozantinib is a safe and effective treatment for people with ...

2. kidneycancer.org kidneycancer.org/trial/a-study-of-abemaciclib-and-cabozantinib-in-people-with-clear-cell-renal-cell-carcinoma-ccrcc/

A Study of Abemaciclib and Cabozantinib in People With ... The researchers are doing this study to find out whether the combination of abemaciclib and cabozantinib is a safe and effective treatment for people with ...

3. mskcc.org mskcc.org/cancer-care/clinical-trials/24-126

A Phase 1b/2 Study of Abemaciclib and Cabozantinib in ... Researchers want to find the best doses of abemaciclib and cabozantinib to use in people with advanced kidney cancer.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39263256/

Effectiveness of Second-Line Cabozantinib in Metastatic ... Conclusions: Cabozantinib remains effective as a 2 L therapy for mccRCC independent of the type of prior 1 L ICI-based combination. Further ...

5. withpower.com withpower.com/trial/phase-2-carcinoma-1-2025-ca853

Abemaciclib + Cabozantinib for Kidney Cancer Cabozantinib shows promising anti-tumor activity in patients with metastatic clear cell renal cell carcinoma (RCC), with a partial response observed in 28% of ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1558767325000199

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.