Axitinib + Anti-OX40 Antibody for Kidney Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for kidney cancer that has spread to other parts of the body. It examines whether axitinib, alone or combined with an anti-OX40 antibody (a biological therapy that aids the immune system in fighting cancer), can halt tumor growth. The aim is to determine if these treatments are more effective together or separately. Suitable participants have kidney cancer that has spread, have undergone kidney removal, and have tried at least one prior cancer treatment. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that axitinib is usually well-tolerated by patients. In one study, about 20% of patients lowered their dose due to side effects, and 8% stopped the treatment completely. This indicates that while some side effects occur, many patients can continue the treatment.

Studies have examined the anti-OX40 antibody PF-04518600 in combination with axitinib for treating kidney cancer. The research included 59 patients and focused on safety. Although specific side effects are not detailed, reaching this trial stage suggests a reasonable safety profile so far.

Overall, both treatments have been studied and deemed safe enough for testing in this trial. Potential participants should consult their doctors to understand all risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for kidney cancer because they offer a fresh approach compared to the standard care options like sunitinib or pazopanib. The combination of axitinib, a tyrosine kinase inhibitor, with an anti-OX40 antibody is particularly promising. The anti-OX40 antibody PF-04518600 targets the OX40 protein on T-cells, enhancing the immune system's ability to attack cancer cells. This dual approach not only inhibits tumor growth through axitinib but also boosts the immune response, potentially leading to more effective and lasting results.

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

This trial will compare two treatment approaches for kidney cancer. In one arm, participants will receive axitinib combined with the anti-OX40 antibody PF-04518600. Research has shown that axitinib, when used with an anti-OX40 antibody, might help treat kidney cancer that has spread. Axitinib blocks certain proteins that aid cancer cell growth, and studies suggest that combining it with the anti-OX40 antibody PF-04518600 may enhance the immune system's ability to fight cancer. In the other arm, participants will receive axitinib with a placebo. Although more research is needed, these findings offer hope that the combination of axitinib and the anti-OX40 antibody could be an effective treatment option. ^{1 2 3 4 5}

Who Is on the Research Team?

Sarmad Sadeghi

Principal Investigator

University of Southern California

Are You a Good Fit for This Trial?

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.

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

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03092856

Axitinib With or Without Anti-OX40 Antibody PF-04518600 ... Giving axitinib with or without anti-OX40 antibody PF-04518600 may work better in treating patients with kidney cancer. Detailed Description. PRIMARY ...

2. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03092856/

Clinical Trial: NCT03092856 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 ...

3. urotoday.com urotoday.com/conference-highlights/esmo-2024/esmo-2024-kidney-cancer/154783-esmo-2024-phase-ii-randomized-double-blind-trial-of-axitinib-pf-04518600-an-ox40-antibody-after-pd1-pdl1-antibody-therapy-in-metastatic-renal-cell-carcinoma-final-analysis.html

Phase II Randomized Double-Blind Trial of Axitinib +/- PF ... Dr. Sarmad Sadeghi presented the final results of a phase II double-blind, randomized trial of axitinib +/- PF 04518600, an OX40 antibody for ...

4. withpower.com withpower.com/trial/phase-3-carcinoma-renal-cell-6-2017-ab07a

Axitinib + Anti-OX40 Antibody for Kidney Cancer The combination of avelumab and axitinib showed promising antitumor activity in treatment-naive patients with advanced renal-cell carcinoma, with 58% of ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9599552/

Treatment of Refractory Metastatic Renal Cell Carcinoma ... cell RCC. The recently published data on axitinib with and without anti-OX40 antibody (pF-04518600) investigated 59 patients in the ...