Pembrolizumab + Axitinib for Kidney Cancer

(NEOPAX Trial)

Recruiting at 2 trial locations

Overseen By Matthew Lee

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must not be taking: Steroids, Immunosuppressants, CYP3A4/5 inducers

Disqualifiers: Immunodeficiency, Autoimmune disease, CNS metastases, others

Stay on Your Current Meds You can continue your current medications while participating

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 34

Duration: 12 weeks

17 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining Pembrolizumab (an immunotherapy drug) and Axitinib (a targeted therapy) can shrink tumor clots in the main vein (Inferior Vena Cava) near the kidney in individuals with kidney cancer. By reducing these clots, the trial seeks to make surgeries safer and improve long-term health outcomes for participants. It is recruiting individuals with clear cell kidney cancer who are planning to undergo surgery. Those advised to have surgery for their kidney cancer might be suitable candidates for this trial. As a Phase 2 trial, it focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use certain drugs that strongly affect liver enzymes (CYP3A4/5 inhibitors or inducers) within 7 days before joining the study.

Is there any evidence suggesting that the combination of Pembrolizumab and Axitinib is likely to be safe for humans?

Research has shown that the combination of pembrolizumab and axitinib is generally well-tolerated by patients. Earlier studies found that side effects were similar to those seen when each drug is used alone, indicating no significant increase in side effects when used together.

Using pembrolizumab and axitinib together has improved outcomes in kidney cancer. In a large study, this combination lowered the risk of death compared to another treatment. Additionally, about 85% of patients experienced some control over their disease, with many showing a reduction in tumor size.

While side effects occur, they are expected and often manageable. Previous studies have provided researchers with a good understanding of its safety. For those considering joining a trial, this information suggests that the treatment is safe enough to continue testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Pembrolizumab and Axitinib for treating kidney cancer because it offers a new approach that targets cancer more aggressively. Pembrolizumab is an immunotherapy drug that boosts the body’s immune response to attack cancer cells, while Axitinib inhibits blood vessel growth that tumors need to grow. By combining these two, there's potential for a more comprehensive attack on the cancer than standard treatments, which often focus on just one of these pathways. This dual-action approach could lead to better outcomes and offer hope for patients with advanced kidney cancer.

What evidence suggests that the combination of Pembrolizumab and Axitinib could be effective for kidney cancer?

Research has shown that using pembrolizumab and axitinib together yields promising results for treating kidney cancer. In this trial, participants will receive the combination as neoadjuvant therapy. One study found that this combination helped patients live longer and slowed cancer growth more effectively than sunitinib. Specifically, it reduced the chance of cancer worsening by 31% and nearly halved the risk of death for patients with advanced kidney cancer. In some cases, patients even saw their cancer completely disappear. These findings suggest that using pembrolizumab and axitinib together might be a good option for shrinking tumors and potentially improving long-term health outcomes. ^{2 6 7 8 9}

Who Is on the Research Team?

Elizabeth R. Kessler

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

Adults with clear cell renal cell carcinoma and a tumor thrombus in the inferior vena cava who are candidates for surgery. They must have good performance status, controlled blood pressure, no major surgeries or radiation therapy within specific time frames before enrollment, and not be on certain medications that affect immune response or blood clotting.

Inclusion Criteria

Stated willingness to comply with all study procedures and be available for the duration of the study

My urologist considers me a good candidate for immediate surgery.

I am a candidate for and agree to have kidney surgery as advised by my urologist.

Exclusion Criteria

I haven't had major surgery or radiation therapy in the last month.

I have had heart problems in the last year.

Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study by subject self-report

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant therapy with Pembrolizumab and Axitinib for 12 weeks

12 weeks

4 cycles of therapy with visits every 21 days

Surgery

Participants undergo definitive surgery within 2 weeks after the end of treatment scan

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including surgical complications and adverse events

4 weeks

Post-operative monitoring up to 30 days

Long-term Follow-up

Participants are monitored for progression-free survival and overall survival up to 1 year

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Axitinib
• Pembrolizumab

Trial Overview

The trial is testing if Pembrolizumab combined with Axitinib can reduce the size of kidney cancer-related blood clots in the vein before surgery. The goal is to see if this pre-surgery treatment leads to fewer surgical complications and better long-term health outcomes like survival without cancer progression.

How Is the Trial Designed?

Group I: Combination Pembrolizumab and Axitinib Experimental Treatment 2 Interventions

Neoadjuvant therapy with the combination of Pembrolizumab and Axitinib will be given for eligible RCC patients with an IVC TT for a total of 12 weeks. Patients will then undergo imaging with a contrast enhanced, diffusion weighted imaging MRI of the abdomen to evaluate the IVC TT response. A CT chest will also be done to ensure there is no progression of disease. Patients can undergo definitive surgery per treating Urologist within 2 weeks (+/- 7 days) after end of treatment scan.

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Cancer League of Colorado

Collaborator

Trials

13

Recruited

450+

Published Research Related to This Trial

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 real-world study of 355 patients with advanced clear cell renal cell carcinoma, the combination of axitinib and pembrolizumab showed a best overall response rate of 47.9% and a one-year overall survival rate of 73.5%.

Treatment-related toxicity was the primary reason for dose adjustments, but over 80% of patients who experienced treatment management events were able to continue their therapy, suggesting that dose holds can be an effective strategy to manage side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Therapy Management and Outcomes of First-Line Axitinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma in the United States. Zakharia, Y., Thomaidou, D., Li, B., et al.[2022]

In a subgroup analysis of 94 Japanese patients with metastatic renal cell carcinoma, the combination of pembrolizumab and axitinib showed improved overall survival and progression-free survival compared to sunitinib, consistent with results from the larger global study.

The safety profile was also favorable, with fewer grade ≥3 treatment-related adverse events in the pembrolizumab-axitinib group (70%) compared to sunitinib (78%), and no deaths from treatment-related adverse events were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus axitinib versus sunitinib in metastatic renal cell carcinoma: outcomes of Japanese patients enrolled in the randomized, phase III, open-label KEYNOTE-426 study. Tamada, S., Kondoh, C., Matsubara, N., et al.[2022]

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]

In a phase 3 trial with 861 patients suffering from advanced clear-cell renal-cell carcinoma, the combination of pembrolizumab and axitinib significantly improved overall survival (89.9% vs. 78.3% at 12 months) compared to sunitinib, with a hazard ratio for death of 0.53.

Patients receiving pembrolizumab plus axitinib also experienced longer progression-free survival (15.1 months vs. 11.1 months) and a higher objective response rate (59.3% vs. 35.7%), indicating that this combination therapy is more effective than sunitinib for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. Rini, BI., Plimack, ER., Stus, V., et al.[2022]

Patients with advanced renal cell carcinoma treated with pembrolizumab plus axitinib experienced a higher incidence of grade 3/4 aminotransferase elevations (22%) compared to those treated with sunitinib (7%), indicating a need for careful monitoring of liver function during treatment.

Despite the higher rates of liver enzyme elevations, most patients (96%) with significant alanine aminotransferase (ALT) increases recovered after treatment interruption, suggesting that with proper management, the adverse effects can be effectively controlled.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization and Management of Treatment-emergent Hepatic Toxicity in Patients with Advanced Renal Cell Carcinoma Receiving First-line Pembrolizumab plus Axitinib. Results from the KEYNOTE-426 Trial. Rini, BI., Atkins, MB., Plimack, ER., et al.[2022]

In a study of 38 patients with metastatic renal cell carcinoma (mRCC) receiving pembrolizumab/axitinib as second-line or later therapy, the treatment showed a median progression-free survival (PFS) of 9.7 months and an objective response rate (ORR) of 25%, indicating its effectiveness even after prior treatments.

The safety profile of pembrolizumab/axitinib was consistent with earlier studies, with 86.8% of patients experiencing adverse events, but no grade 5 adverse events were reported, suggesting it is a relatively safe option for patients who have already undergone other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes With Combination Pembrolizumab and Axitinib in Second and Further Line Treatment of Metastatic Renal Cell Carcinoma. Dizman, N., Austin, M., Considine, B., et al.[2023]

The combination of axitinib and pembrolizumab is tolerable and shows promising antitumor activity in patients with treatment-naive advanced renal cell carcinoma, with 73% of patients achieving an objective response.

In a study involving 52 patients, no unexpected toxicities were observed, although 65% experienced grade 3 or worse treatment-related adverse events, indicating that while the treatment is effective, it does carry some risk of significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial. Atkins, MB., Plimack, ER., Puzanov, I., et al.[2023]

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]

In a study of 52 treatment-naïve patients with advanced renal cell carcinoma receiving axitinib and pembrolizumab, higher baseline levels of immune-related biomarkers like CD8 and CXCL10 were associated with longer progression-free survival and better response rates.

The presence of IL6 at baseline was linked to shorter progression-free survival, suggesting that certain biomarkers could help predict treatment outcomes and warrant further investigation in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Angiogenic and Immune-Related Biomarkers and Outcomes Following Axitinib/Pembrolizumab Treatment in Patients with Advanced Renal Cell Carcinoma. Martini, JF., Plimack, ER., Choueiri, TK., et al.[2023]

In a study involving 861 patients with advanced renal cell carcinoma, pembrolizumab plus axitinib demonstrated significantly better overall survival and progression-free survival compared to sunitinib monotherapy, with a median follow-up of 30.6 months.

The combination treatment was associated with manageable adverse events, with no new treatment-related deaths reported, reinforcing its safety profile as a first-line therapy for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial. Powles, T., Plimack, ER., Soulières, D., et al.[2021]

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