Tivozanib + Pembrolizumab for Kidney Cancer

(STRIKE Trial)

Recruiting at 61 trial locations

Overseen By Aishwarya Vijendran

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alliance for Clinical Trials in Oncology

Must not be taking: Corticosteroids, Immunosuppressive drugs

Disqualifiers: Uncontrolled hypertension, Cardiac disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 4

Duration: 48 weeks

1040 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase III trial compares the effect of adding tivozanib to standard therapy pembrolizumab versus pembrolizumab alone for the treatment of patients with high-risk renal cell carcinoma (RCC). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Tivozanib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals tumor cells to multiply. This helps stop the spread of tumor cells. Giving pembrolizumab and tivozanib together may work better than pembrolizumab alone in treating patients with RCC.

Will I have to stop taking my current medications?

The trial requires that you stop taking any strong CYP3A4 inducers (a type of medication that affects how drugs are processed in the body) at least 14 days before starting the study treatment. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination Tivozanib and Pembrolizumab for kidney cancer?

Pembrolizumab has shown strong effectiveness in treating kidney cancer, especially in patients with metastatic disease, by improving disease-free survival after surgery. Tivozanib, a targeted drug for kidney cancer, has been approved for use in patients with advanced disease and has shown promising results in clinical trials, with a median progression-free survival of 11.7 months. ^{1 2 3 4 5}

Is the combination of Tivozanib and Pembrolizumab safe for treating kidney cancer?

Pembrolizumab, used in combination with other drugs, has been associated with some kidney-related side effects, such as acute kidney injury and tubulointerstitial nephritis (a type of kidney inflammation). However, these side effects are not common and can often be managed with treatment adjustments. ^{6 7 8 9 10}

How is the drug Tivozanib + Pembrolizumab unique for kidney cancer?

Tivozanib is a unique drug for kidney cancer because it specifically targets and inhibits all vascular endothelial growth factor receptors (VEGFRs), which are involved in the growth of blood vessels that feed tumors. This makes it different from other treatments that may not be as selective or potent in targeting these receptors. When combined with Pembrolizumab, an immunotherapy drug that helps the immune system attack cancer cells, this combination offers a novel approach to treating advanced kidney cancer. ^{3 4 11 12 13}

Eligibility Criteria

This trial is for patients with high-risk renal cell carcinoma who've had surgery to remove the cancer within the last 4-16 weeks without complications. It's open to those with certain stages and grades of kidney cancer, including cases where it has not spread (M0) or there's no evidence of disease after metastasis treatment.

Inclusion Criteria

My cancer is in stage T3 but hasn't spread to lymph nodes or other parts.

My kidney cancer was confirmed by a lab test and I've had surgery to remove it.

My cancer is large but hasn't spread to lymph nodes or other parts.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive pembrolizumab and tivozanib or pembrolizumab alone in cycles repeating every 12 weeks for up to 4 cycles

48 weeks

Multiple visits for IV administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

Every 4 months for 2 years, then every 6 months for 3 years, then annually

Treatment Details

Interventions

• Pembrolizumab
• Tivozanib

Trial Overview The study is testing if adding Tivozanib, a drug that blocks tumor growth signals, to Pembrolizumab, an immunotherapy drug helping the immune system fight cancer, provides better outcomes than using Pembrolizumab alone after kidney cancer surgery.

Participant Groups

Group I: Arm 2 (pembrolizumab + tivozanib) Experimental Treatment 7 Interventions

Patients receive pembrolizumab IV on days 1 and 43 of each cycle and tivozanib PO QD on days 1-21, days 29-49, and days 57-77 of each cycle for up to 6 months. Cycles repeat every 12 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and MRI or CT throughout the trial and may undergo tissue biopsy on study.

Group II: Arm 1 (Pembrolizumab) Active Control 6 Interventions

Patients receive pembrolizumab IV on days 1 and 43 of each cycle, or on days 1, 22, 43 and 64 of each cycle. Cycles repeat every 12 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and MRI or CT throughout the trial and may undergo tissue biopsy on study.

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

Findings from Research

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]

Adjuvant pembrolizumab significantly improves disease-free survival in patients with high-risk renal cell carcinoma (RCC) after surgery, as shown in the KEYNOTE 564 trial.

Pembrolizumab is an effective and well-tolerated treatment option for patients with surgically resected RCC, paving the way for future research on patient selection and biomarkers for therapy response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant therapy for patients with renal cell carcinoma following surgery: a focus on pembrolizumab. Serzan, M., Atkins, MB.[2022]

Tivozanib is a newly approved treatment for advanced renal cell carcinoma (RCC) that targets multiple vascular endothelial growth factor receptors (VEGFR-1, -2, and -3), showing a promising safety profile and clinical benefits for patients who have already undergone multiple therapies.

The ongoing TINIVO-2 study is exploring the combination of tivozanib with nivolumab, which could potentially enhance treatment options for patients who have not responded to immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tivozanib for the treatment of advanced renal cell carcinoma. Chatzkel, J., Ramnaraign, B., Sonpavde, G.[2022]

In the KEYNOTE-B61 trial involving 158 patients with advanced non-clear-cell renal cell carcinoma, the combination of pembrolizumab and lenvatinib demonstrated a 49% objective response rate, indicating significant antitumor activity as a first-line treatment.

The safety profile was consistent with previous studies, with 51% of patients experiencing grade 3-4 treatment-related adverse events, primarily hypertension, but no deaths were attributed to the treatment itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus lenvatinib as first-line therapy for advanced non-clear-cell renal cell carcinoma (KEYNOTE-B61): a single-arm, multicentre, phase 2 trial. Albiges, L., Gurney, H., Atduev, V., et al.[2023]

In the CLEAR study involving 352 patients, the combination of lenvatinib and pembrolizumab showed a manageable safety profile, with common adverse reactions including fatigue (63.1%), diarrhea (61.9%), and hypertension (56.3%).

Most adverse reactions occurred within approximately 5 months of starting treatment, and effective management strategies such as monitoring and dose modifications were identified to ensure patient safety and support ongoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization and Management of Adverse Reactions From the CLEAR Study in Advanced Renal Cell Carcinoma Treated With Lenvatinib Plus Pembrolizumab. Motzer, R., George, S., Merchan, JR., et al.[2023]

Pembrolizumab, an immune checkpoint inhibitor for non-small cell lung carcinoma, has been linked to adverse renal outcomes, including acute kidney injury.

In a reported case, a patient developed acute tubulointerstitial nephritis after starting pembrolizumab, and while renal function improved with long-term corticosteroid treatment after discontinuation of the drug, it only improved partially.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Tubulointerstitial Nephritis: A Case Report on Rare Adverse Effect of Pembrolizumab. Basnet, S., Dhital, R., Tharu, B.[2020]

In a phase II study involving 110 patients with advanced clear cell renal cell carcinoma (ccRCC), pembrolizumab demonstrated a 36.4% objective response rate, indicating significant antitumor activity as a first-line treatment.

The treatment was generally well-tolerated, with 30% of patients experiencing grade 3-5 adverse events, primarily colitis and diarrhea, which aligns with safety profiles observed in other cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Label, Single-Arm Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Clear Cell Renal Cell Carcinoma. McDermott, DF., Lee, JL., Bjarnason, GA., et al.[2022]

References

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

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

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

Adjuvant therapy for patients with renal cell carcinoma following surgery: a focus on pembrolizumab. [2022]

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

Tivozanib for the treatment of advanced renal cell carcinoma. [2022]

4. China pubmed.ncbi.nlm.nih.gov

Tivozanib: a novel VGFR inhibitor for kidney cancer. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Tumor control with PD-1 inhibition in a patient with concurrent metastatic melanoma and renal cell carcinoma. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus lenvatinib as first-line therapy for advanced non-clear-cell renal cell carcinoma (KEYNOTE-B61): a single-arm, multicentre, phase 2 trial. [2023]

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

Characterization and Management of Adverse Reactions From the CLEAR Study in Advanced Renal Cell Carcinoma Treated With Lenvatinib Plus Pembrolizumab. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Acute Tubulointerstitial Nephritis: A Case Report on Rare Adverse Effect of Pembrolizumab. [2020]

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

Open-Label, Single-Arm Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Clear Cell Renal Cell Carcinoma. [2022]

10. Italy pubmed.ncbi.nlm.nih.gov

[Immunotherapy in kidney cancer: how it has changed and what are the challenges for the nephrologist - focus on pembrolizumab]. [2021]

11. Spain pubmed.ncbi.nlm.nih.gov

Tivozanib: a new treatment option for renal cell carcinoma. [2018]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Tivozanib in First-Line mRCC: A Multicenter Compassionate-Use Study (Meet-Uro 16). [2021]

13. Spain pubmed.ncbi.nlm.nih.gov

Tivozanib: practical implications for renal cell carcinoma and other solid tumors. [2017]