Nivolumab + Axitinib for Kidney Cancer

Recruiting at 3 trial locations

Overseen By Matthew Zibelman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Fox Chase Cancer Center

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Brain metastases, Autoimmune disease, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

98 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a Phase I/II, open-label, multi-center study of axitinib in combination with nivolumab in patients with previously treated and untreated advanced RCC. This clinical study will be composed of a dose finding phase (Phase I) and two parallel dose expansion phases (Phase II). The dose finding phase will assess the safety of the combination and establish a recommended phase II dose (RP2D, the highest tested dose that is declared safe and tolerable by the Investigators and the Sponsor Investigator) in patients with advanced RCC who have received prior systemic therapy for metastatic disease. Phase II will evaluate the efficacy of the combination at the RP2D in two parallel expansion cohorts in both previously treated and treatment naïve patients.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that you cannot use certain drugs that strongly affect liver enzymes (CYP3A4/5 inhibitors and inducers) and should be cautious with drugs that may harm the liver. It's best to discuss your current medications with the trial team.

Is the combination of Nivolumab and Axitinib safe for humans?

Axitinib, when used in combination with immune checkpoint inhibitors like pembrolizumab or avelumab, has shown a tolerable safety profile in treating advanced kidney cancer. Common side effects include diarrhea, high blood pressure, fatigue, nausea, and vomiting, which require monitoring and management to minimize treatment interruptions. ^{1 2 3 4 5}

How is the drug combination of Nivolumab and Axitinib unique for treating kidney cancer?

The combination of Nivolumab and Axitinib is unique because it combines an immune checkpoint inhibitor (Nivolumab) with a targeted therapy (Axitinib), offering a novel approach by enhancing the immune system's ability to fight cancer while also inhibiting blood vessel growth that tumors need to grow. This dual mechanism may provide a more effective treatment option compared to using either drug alone. ^{6 7 8 9 10}

What data supports the effectiveness of the drug combination Nivolumab and Axitinib for kidney cancer?

Research shows that similar drug combinations, like axitinib with pembrolizumab, have been effective in treating advanced kidney cancer, with a high response rate and improved survival compared to other treatments. This suggests that combining axitinib with immune checkpoint inhibitors, like nivolumab, could also be beneficial. ^{10 11 12 13 14}

Are You a Good Fit for This Trial?

Adults over 18 with advanced kidney cancer, specifically clear cell renal cell carcinoma. Participants can be new to treatment or have had previous therapy but must have measurable cancer lesions and good organ function. They should not have uncontrolled high blood pressure, autoimmune diseases, recent major surgery or radiation, active infections like HIV/HBV/HCV, or be pregnant.

Inclusion Criteria

My bone marrow, kidney, and liver are functioning well.

I am older than 18 years.

I have received specific treatments for my metastatic disease or was treated with high dose interleukin-2.

Exclusion Criteria

I have active brain or spinal cord cancer symptoms.

I haven't taken steroids or immunosuppressants in the last 14 days.

I have no major issues with my digestive system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Finding (Phase I)

Assess the safety of the combination and establish a recommended phase II dose (RP2D) in patients with advanced RCC who have received prior systemic therapy for metastatic disease

Up to 15 months

Dose Expansion (Phase II)

Evaluate the efficacy of the combination at the RP2D in two parallel expansion cohorts in both previously treated and treatment naïve patients

Up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 25 months

What Are the Treatments Tested in This Trial?

Interventions

• Axitinib
• Nivolumab

Trial Overview The study is testing the combination of Nivolumab (an immunotherapy drug) and Axitinib (a medication that inhibits blood vessel growth in tumors) in patients with advanced kidney cancer. It includes a Phase I part to find safe doses and a Phase II part to test effectiveness in both new and previously treated patients.

How Is the Trial Designed?

Group I: Phase II patients: cohort 2 Experimental Treatment 2 Interventions

Phase II cohort 2 patients must not have received prior systemic therapy for advanced RCC.

Group II: Phase II patients: cohort 1 Experimental Treatment 2 Interventions

Phase II cohort 1 patients must have received at least 1 prior tyrosine kinase inhibitor for RCC.

Group III: Phase I patients Experimental Treatment 2 Interventions

Phase I patients must have received at least 1 prior tyrosine kinase inhibitor for RCC.

Axitinib is already approved in European Union, United States, United Kingdom for the following indications:

Approved in European Union as Inlyta for:

• Renal cell carcinoma

Approved in United States as Inlyta for:

• Advanced renal cell carcinoma

Approved in United Kingdom as Inlyta for:

• Advanced renal cell carcinoma

Who Is Running the Clinical Trial?

Fox Chase Cancer Center

Lead Sponsor

Trials

236

Recruited

39,300+

Published Research Related to This Trial

In the phase III JAVELIN Renal 101 trial, avelumab plus axitinib demonstrated significantly improved progression-free survival (PFS) of 13.9 months compared to 8.5 months for sunitinib, indicating better efficacy in treating advanced renal cell carcinoma.

The overall survival (OS) trend also favored avelumab plus axitinib, with a hazard ratio of 0.79 compared to sunitinib, although the data is still immature and requires further follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended follow-up from JAVELIN Renal 101: subgroup analysis of avelumab plus axitinib versus sunitinib by the International Metastatic Renal Cell Carcinoma Database Consortium risk group in patients with advanced renal cell carcinoma. Haanen, JBAG., Larkin, J., Choueiri, TK., et al.[2023]

The combination of axitinib and pembrolizumab shows a high response rate of 73% in patients with previously untreated advanced renal cell carcinoma, indicating strong efficacy for this treatment regimen.

This finding suggests that the dual approach of targeting both tumor growth and immune response may be effective in managing advanced kidney cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib plus Pembrolizumab Is Effective in Renal Cell Carcinoma. [2019]

Combination therapies using immune checkpoint inhibitors, such as axitinib plus pembrolizumab, have shown improved outcomes compared to traditional sequential monotherapy in patients with metastatic renal cell carcinoma.

Phase III trials indicate that these combination regimens significantly enhance both progression-free survival and overall survival, addressing the issue of drug resistance seen with single-agent treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus axitinib combination and the paradigm change in the treatment of advanced renal cell carcinoma. Spisarová, M., Melichar, B., Vitásková, D., et al.[2021]

The combination of avelumab and axitinib showed promising antitumor activity in treatment-naive patients with advanced renal-cell carcinoma, with 58% of patients achieving confirmed objective responses in the study involving 55 participants.

The safety profile of the combination treatment was manageable, with adverse events similar to those seen with each drug alone, and the maximum tolerated dose was established as avelumab 10 mg/kg every 2 weeks and axitinib 5 mg twice daily.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial. Choueiri, TK., Larkin, J., Oya, M., et al.[2022]

The combination of avelumab and axitinib has shown superior response rates and progression-free survival in treatment-naïve patients with metastatic renal cell carcinoma compared to sunitinib, based on the Javelin 101 phase III trial.

Despite the improved response rates, there was no significant difference in overall survival after 11.6 months of follow-up, and the safety profile of avelumab/axitinib was found to be tolerable with manageable adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab and axitinib in the treatment of renal cell carcinoma: safety and efficacy. Leslie, I., Boos, LA., Larkin, J., et al.[2021]

Axitinib combined with immune checkpoint inhibitors (ICI) like pembrolizumab or avelumab is now approved for treating advanced renal cell carcinoma, but distinguishing between adverse events (AEs) caused by each treatment is crucial for optimizing therapy.

Experts identified specific AEs such as diarrhea, hepatic toxicity, fatigue, and cardiovascular issues that require unique management strategies when using axitinib-ICI combinations, emphasizing the need for careful clinical monitoring and tailored treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib plus immune checkpoint inhibitor: evidence- and expert-based consensus recommendation for treatment optimisation and management of related adverse events. Grünwald, V., Voss, MH., Rini, BI., et al.[2021]

In a long-term study of 52 patients with advanced renal-cell carcinoma, the combination of axitinib and pembrolizumab showed promising efficacy, with a median progression-free survival of 23.5 months and an overall response rate of 73.1%.

After nearly 4 years of follow-up, the treatment was associated with significant clinical benefits and no new safety concerns, although 73.1% of patients experienced grade III/IV adverse events, leading to treatment discontinuation in 38.5% of cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib plus pembrolizumab in patients with advanced renal-cell carcinoma: Long-term efficacy and safety from a phase Ib trial. Atkins, MB., Plimack, ER., Puzanov, I., et al.[2021]

Axitinib is an effective second-line treatment for advanced renal cell carcinoma (RCC), showing significantly prolonged median progression-free survival compared to sorafenib in the phase III AXIS trial.

The tolerability profile of axitinib is manageable, with common side effects including diarrhea, hypertension, and fatigue, making it a viable option for patients who have already received other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib: a review in advanced renal cell carcinoma. Keating, GM.[2018]

Recent randomized trials have shown that the combination of pembrolizumab and axitinib significantly improves survival in patients with metastatic clear-cell renal cell carcinoma, establishing it as a new standard of care.

This treatment is recommended for all treatment-naïve patients, regardless of their risk group, according to updated guidelines from the European Association of Urology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint Inhibition Is the New Backbone in First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma. Albiges, L., Powles, T., Staehler, M., et al.[2020]

The combination of ipilimumab and nivolumab is considered a feasible first-line treatment for metastatic renal cell carcinoma, showing an acceptable safety profile compared to sunitinib monotherapy, based on a systematic review and meta-analysis of four randomized controlled trials.

Different immune-based combinations, including nivolumab plus ipilimumab and pembrolizumab plus axitinib, exhibit varying toxicity profiles, highlighting the importance of personalized treatment choices and the need for improved management of immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of immune-based combinations in patients with advanced renal cell carcinoma: a systematic review and meta-analysis. Massari, F., Mollica, V., Rizzo, A., et al.[2022]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Extended follow-up from JAVELIN Renal 101: subgroup analysis of avelumab plus axitinib versus sunitinib by the International Metastatic Renal Cell Carcinoma Database Consortium risk group in patients with advanced renal cell carcinoma. [2023]

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

Axitinib plus Pembrolizumab Is Effective in Renal Cell Carcinoma. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus axitinib combination and the paradigm change in the treatment of advanced renal cell carcinoma. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

Clinical outcomes of second-line treatment following prior targeted therapy in patients with metastatic renal cell carcinoma: a comparison of axitinib and nivolumab. [2020]

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

Axitinib for the treatment of metastatic renal cell carcinoma: recommendations for therapy management to optimize outcomes. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Avelumab and axitinib in the treatment of renal cell carcinoma: safety and efficacy. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Axitinib plus immune checkpoint inhibitor: evidence- and expert-based consensus recommendation for treatment optimisation and management of related adverse events. [2021]

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

Efficacy and safety of axitinib for metastatic renal cell carcinoma: Real-world data on patients with renal impairment. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Axitinib plus pembrolizumab in patients with advanced renal-cell carcinoma: Long-term efficacy and safety from a phase Ib trial. [2021]

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

Axitinib: a review in advanced renal cell carcinoma. [2018]

12. Australia pubmed.ncbi.nlm.nih.gov

A comparative study on nivolumab and axitinib as secondary treatment in patients with metastatic renal cell carcinoma: A multi-institutional retrospective study in Japan. [2023]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Updated European Association of Urology Guidelines on Renal Cell Carcinoma: Immune Checkpoint Inhibition Is the New Backbone in First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma. [2020]

14. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of immune-based combinations in patients with advanced renal cell carcinoma: a systematic review and meta-analysis. [2022]