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

Trial Summary

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.

What data supports the effectiveness of the drug combination Abemaciclib and Cabozantinib for kidney cancer?

Cabozantinib has been shown to be effective in treating advanced kidney cancer, improving survival and response rates in patients, as seen in the METEOR trial. It is approved for use in advanced kidney cancer, which suggests it could be beneficial when combined with other treatments like Abemaciclib. ^{1 2 3 4 5}

What safety information is available for cabozantinib in combination treatments?

Cabozantinib, when used in combination with other drugs like nivolumab, has a safety profile that is generally manageable with proper care. Common side effects include diarrhea, fatigue, and skin reactions, and they can often be managed with dose adjustments and supportive care. ^{4 6 7 8 9}

What makes the drug combination of Abemaciclib and Cabozantinib unique for kidney cancer?

The combination of Abemaciclib and Cabozantinib is unique for kidney cancer because it combines two different mechanisms: Abemaciclib, a CDK4/6 inhibitor that blocks cancer cell division, and Cabozantinib, a tyrosine kinase inhibitor that targets multiple pathways involved in cancer growth and resistance. This dual approach may offer a novel way to tackle kidney cancer compared to existing treatments that typically focus on single pathways. ^{1 4 8 10 11}

What is the purpose of this trial?

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 metastatic clear cell renal cell carcinoma (ccRCC). The researchers will test different doses of the study drugs to find the highest doses that cause few or mild side effects in participants.

Research Team

Martin Voss, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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 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

Findings from Research

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]

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]

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 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]

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]

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 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 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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical use of cabozantinib in the treatment of advanced kidney cancer: efficacy, safety, and patient selection. [2022]

2. England pubmed.ncbi.nlm.nih.gov

A phase I study of cabozantinib (XL184) in patients with renal cell cancer. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non-Clear-Cell Renal Cell Carcinoma and Genomic Correlates. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. [2023]

5. England 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. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Management of adverse events associated with cabozantinib plus nivolumab in renal cell carcinoma: A review. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

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

11. Japan pubmed.ncbi.nlm.nih.gov

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