Axitinib + Anti-OX40 Antibody for Kidney Cancer

Recruiting at 9 trial locations

Overseen By Cheryl Kefauver, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Southern California

Must not be taking: mTOR inhibitors, Corticosteroids

Disqualifiers: Brain metastases, Autoimmune disorders, Infections, others

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: 3

Duration: Up to 180 days

62 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you should avoid using strong CYP3A4/5 inhibitors (a type of enzyme blocker) and certain steroids, as they may interfere with the study drugs. It's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug Axitinib + Anti-OX40 Antibody for kidney cancer?

Axitinib has been shown to be effective in treating advanced kidney cancer, especially in patients who have already tried other treatments. It works by blocking certain proteins that help cancer cells grow, and has been used successfully in combination with other drugs to improve patient outcomes. ^{1 2 3 4 5}

Is the combination of Axitinib and Anti-OX40 Antibody safe for humans?

Axitinib, also known as Inlyta, has been studied for safety in patients with advanced kidney cancer. Common side effects include diarrhea, high blood pressure, fatigue, decreased appetite, nausea, voice changes, hand-foot syndrome, and low thyroid function. The safety of the Anti-OX40 Antibody in combination with Axitinib specifically is not detailed in the provided research. ^{1 3 4 5 6}

What makes the drug Axitinib + Anti-OX40 Antibody unique for kidney cancer?

This treatment combines Axitinib, a drug that blocks specific proteins (VEGF receptors) to stop cancer growth, with an Anti-OX40 Antibody, which may enhance the immune system's ability to fight cancer. This combination is unique because it targets both the cancer cells directly and boosts the body's immune response, offering a potentially more effective approach than using either component alone. ^{1 3 5 7 8}

What is the purpose of this trial?

This randomized phase II trial studies how well axitinib with or without anti-OX40 antibody PF-04518600 work in treating patients with kidney cancer that has spread to other parts of the body. Biological therapies, such as anti-OX40 antibody PF-04518600, use substances made from living organisms that may may stimulate the immune system in different ways and stop tumor cells from growing. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving axitinib with or without anti-OX40 antibody PF-04518600 may work better in treating patients with kidney cancer.

Research Team

Sarmad Sadeghi

Principal Investigator

University of Southern California

Eligibility Criteria

This trial is for adults with metastatic kidney cancer who've had a nephrectomy, have measurable disease, and proper organ function. They must not be pregnant or breastfeeding, use effective contraception, and can't have brain metastases requiring steroids, active autoimmune diseases, recent major surgeries or certain medical conditions.

Inclusion Criteria

Criterion: You have a measurable disease according to specific guidelines for evaluating tumors.

I can take care of myself but might not be able to do heavy physical work.

Women of childbearing potential must have a negative serum pregnancy test within 24 hours prior to the administration of the investigational product

Exclusion Criteria

I am currently taking certain medications.

You have a history of or currently have autoimmune disorders.

I haven't had any cancer except for treatable ones in the last 3 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive axitinib orally twice daily and either anti-OX40 antibody PF-04518600 or placebo intravenously, with courses repeating every 14 days

Up to 180 days

Bi-weekly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

180 days

3 visits (in-person) at 30, 90, and 180 days

Treatment Details

Interventions

• Anti-OX40 Antibody PF-04518600
• Axitinib

Trial Overview The study tests axitinib alone versus in combination with anti-OX40 antibody PF-04518600 to see which is better at treating metastatic kidney cancer. Axitinib blocks enzymes needed for tumor growth; the antibody may stimulate the immune system to fight cancer cells.

Participant Groups

Group I: Arm I (axitinib, anti-OX40 antibody PF-04518600) Experimental Treatment 3 Interventions

Patients receive axitinib PO BID on days 1-14 and anti-OX40 antibody PF-04518600 IV over 60 minutes on day 1 beginning with course 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm II (axitinib, placebo) Active Control 3 Interventions

Patients receive axitinib as in Arm I and placebo IV on day 1 beginning with course 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

Axitinib is a newly approved targeted therapy for advanced renal cell cancer that shows greater potency in inhibiting VEGFR1-3 compared to earlier treatments, significantly improving patient outcomes based on phase II and III clinical trials.

The drug has a manageable toxicity profile and is unique in allowing for dose titration, making it a recommended standard treatment for patients who have previously undergone antiangiogenic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axitinib: a review of its safety and efficacy in the treatment of adults with advanced renal cell carcinoma. Gross-Goupil, M., François, L., Quivy, A., 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]

Axitinib demonstrated antitumor activity in patients with metastatic renal cell carcinoma (mRCC) who were refractory to prior therapies, achieving an objective response rate of 22.6% and a median duration of response of 17.5 months in a study of 62 patients.

The treatment was generally well-tolerated, with manageable mild to moderate adverse effects, including hand-foot syndrome and hypertension, indicating that axitinib could be a viable option for patients who have not responded to other VEGF-targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of axitinib in sorafenib-refractory metastatic renal cell carcinoma. Rini, BI., Wilding, G., Hudes, G., et al.[2018]

References

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

Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study. [2018]

2. 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]

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

Key predictive factors of axitinib (AG-013736)-induced proteinuria and efficacy: a phase II study in Japanese patients with cytokine-refractory metastatic renal cell Carcinoma. [2022]

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

Axitinib: a review of its safety and efficacy in the treatment of adults with advanced renal cell carcinoma. [2021]

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

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

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

Phase II study of axitinib in sorafenib-refractory metastatic renal cell carcinoma. [2018]

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

REVERSIBLE RETINAL TOXICITY IN A PATIENT TAKING AXITINIB. [2021]

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

Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. [2022]