Tivozanib + Pembrolizumab for Kidney Cancer

(STRIKE Trial)

Recruiting at 344 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding tivozanib to pembrolizumab is more effective than using pembrolizumab alone for treating kidney cancer. Pembrolizumab helps the immune system fight cancer cells, while tivozanib, a targeted therapy, blocks signals that prompt tumor cells to grow. The trial aims to determine if the combination more effectively prevents kidney cancer from spreading. It seeks participants with high-risk kidney cancer who have undergone surgery to remove the tumor and currently show no evidence of disease. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have safely used pembrolizumab to treat various cancers, including kidney cancer (renal cell carcinoma or RCC). This treatment, known as immunotherapy, helps the immune system fight cancer cells. Most patients tolerate it well, though some have experienced side effects like tiredness and nausea.

Research has shown that tivozanib is generally well-tolerated in advanced kidney cancer. However, when combined with nivolumab, about 32% of patients experienced serious side effects, such as high blood pressure and diarrhea.

The combination of pembrolizumab and tivozanib remains under study, but both drugs have demonstrated relative safety individually. It is important to consult a healthcare professional about potential risks and benefits before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for kidney cancer?

Researchers are excited about the combination of tivozanib and pembrolizumab for kidney cancer because it offers a novel approach to treatment. Unlike standard therapies that typically involve either surgery or single-agent immunotherapy, this combination targets cancer cells in two different ways. Pembrolizumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells, while tivozanib is a tyrosine kinase inhibitor that blocks signals needed for tumors to grow. This dual-action strategy has the potential to enhance treatment effectiveness and improve patient outcomes by attacking the cancer from multiple angles.

What evidence suggests that this trial's treatments could be effective for kidney cancer?

In this trial, participants will receive either pembrolizumab alone or a combination of pembrolizumab and tivozanib. Studies have shown that pembrolizumab, a type of immunotherapy, helps the body's immune system fight kidney cancer by finding and attacking cancer cells. Research suggests that combining tivozanib with pembrolizumab might enhance this effect. Tivozanib blocks certain proteins that aid cancer cell growth. Early results indicate that this combination could be more effective than pembrolizumab alone. In past studies, similar drug combinations demonstrated high success rates in treating advanced kidney cancer. The goal of this combination is to better stop the cancer from growing and spreading. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06661720

NCT06661720 | Testing the Addition of the Anti-Cancer ... This phase III trial compares the effect of adding tivozanib to standard therapy pembrolizumab versus pembrolizumab alone for the treatment of patients with ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11224966/

Efficacy, Safety, and Tolerability of Tivozanib in Heavily ... Tivozanib has modest efficacy in heavily pretreated patients with advanced renal cell carcinoma. Patients with relatively indolent disease and prior prolonged ...

3. withpower.com withpower.com/trial/phase-3-stage-iii-renal-pelvis-cancer-ajcc-v8-10-2024-419cd

Tivozanib + Pembrolizumab for Kidney Cancer The combination of axitinib and pembrolizumab shows a high response rate of 73% in patients with previously untreated advanced renal cell carcinoma, indicating ...

4. targetedonc.com targetedonc.com/view/assessing-tivozanib-efficacy-in-metastatic-rcc-treatment

Assessing Tivozanib Efficacy in Metastatic RCC Treatment During a live event, Sumanta K. Pal, MD, discussed lenvatinib dosing and tivozanib efficacy for patients with metastatic renal cell carcinoma.

5. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/549235

Testing the Addition of the Anti-Cancer Drug Tivozanib to ... This phase III trial compares the effect of adding tivozanib to standard therapy pembrolizumab versus pembrolizumab alone for the treatment of patients with ...

6. kcrs.kidneycan.org kcrs.kidneycan.org/wp-content/uploads/2025/07/KCRS25-Abstract-Book-7.14.25.pdf

KCRS25 Methods. Adults with previously untreated, advanced nccRCC and measurable disease per RECIST v1.1 received pembrolizumab.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0140673624017586

Articles Tivozanib plus nivolumab versus ... Serious adverse events occurred in 54 (32%) of 168 patients receiving tivozanib–nivolumab and 64 (37%) of 171 patients receiving tivozanib ...