Avelumab + AVB-S6-500 for Bladder Cancer

(COAXIN Trial)

Overseen By Ingrid Block

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Oklahoma

Must not be taking: Anti-PD-1, PD-L1, Corticosteroids, Immunosuppressants

Disqualifiers: Active infection, Autoimmune disease, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effects of a combination treatment using avelumab (an immunotherapy drug) and AVB-S6-500 (an experimental treatment) for individuals with advanced bladder cancer, specifically urothelial carcinoma. Researchers seek to understand how this treatment affects those who have not responded to other cancer therapies. It may suit individuals whose bladder cancer has progressed after previous treatment and who have measurable tumors. As a Phase 1 trial, the research focuses on understanding how the treatment works in participants, offering them the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on certain treatments like other anticancer drugs or high-dose corticosteroids within 28 days before starting the trial.

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

Research has shown that using avelumab with AVB-S6-500 is generally safe. In one study, patients tolerated this combination well, even at varying doses. Another study found avelumab safe for people with bladder cancer, as the FDA has already approved it for treating certain types of this cancer. These results suggest the treatment is manageable, though some side effects might occur. Discussing potential risks and benefits with a doctor is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Avelumab and AVB-S6-500 for bladder cancer because it offers a novel approach compared to standard treatments like chemotherapy and immune checkpoint inhibitors alone. Avelumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. What makes this treatment unique is the addition of AVB-S6-500, which targets a specific protein involved in cancer cell growth and survival. This dual approach could potentially enhance the immune response and directly inhibit tumor growth, offering new hope for improved outcomes in bladder cancer patients.

What evidence suggests that this treatment might be an effective treatment for bladder cancer?

Research has shown that avelumab, when used as a maintenance treatment for advanced bladder cancer, can extend patient survival. In one study, patients taking avelumab lived an average of 21.4 months, compared to 14.3 months for those not taking it. Avelumab also effectively delays cancer progression.

In this trial, participants will receive a combination of avelumab and AVB-S6-500. AVB-S6-500 is a new treatment designed to block a protein called AXL, which aids cancer cell growth. Early research indicates that AVB-S6-500 successfully neutralizes another protein, Gas6, which interacts with AXL. Although the studies involved a small number of participants, initial findings suggest the combination of avelumab and AVB-S6-500 is promising and safe. ^{2 3 6 7 8}

Who Is on the Research Team?

Abhishek Tripathi, MD

Principal Investigator

Stephenson Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with advanced urothelial cancer that's inoperable or has spread, and who have already had platinum-based chemo but the cancer got worse. They must be able to perform daily activities with some limitations (ECOG ≤2), provide a tumor sample, and agree to contraception. Excluded are those on recent anticancer drugs, steroids, or with certain other health issues like untreated brain metastases or active infections.

Inclusion Criteria

My cancer progressed after platinum-based treatment.

Patients who are able to understand and sign the informed consent form.

Ability to comply with protocol

Exclusion Criteria

I haven't taken high-dose steroids or immunosuppressants in the last 28 days.

Pregnant or lactating, or intending to become pregnant during the study

I have not received a live vaccine recently and do not plan to during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive avelumab and AVB-S6-500 by vein every two weeks. Dose adjustments are made based on the dose level enrolled.

up to 2 years

Bi-weekly visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion for up to one year

up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• AVB-S6-500
• Avelumab

Trial Overview The trial is testing the safety and effects of combining two treatments: Avelumab (an immunotherapy drug) and AVB-S6-500 (a new therapy) for patients whose bladder cancer has worsened after chemotherapy. The goal is to see if this combination helps more than current treatments.

How Is the Trial Designed?

Group I: Avelumab + AVB-S6-500 Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

University of Oklahoma

Lead Sponsor

Trials

484

Recruited

95,900+

Aravive, Inc.

Industry Sponsor

Trials

9

Recruited

590+

EMD Serono

Industry Sponsor

Trials

147

Recruited

27,800+

Dr. Shepard

EMD Serono

Chief Medical Officer since 2021

MD from University of Cincinnati Medical School, Fellowships in Hematology and Oncology at University of Chicago Hospitals and Clinics

Miguel Fernández Alcalde

EMD Serono

Chief Executive Officer

Bachelor's Degree in Pharmacy from the University Complutense in Madrid, MBA from the University of Alcalá de Henares, Master's Degree in Management from IESE Business School

Citations

1. bcan.org bcan.org/clinicaltrials/avelumab-in-combination-with-avb-s6-500-in-patients-with-advanced-urothelial-carcinoma/

Avelumab in Combination With AVB-S6-500 in Patients ... The purpose of this research study is to test the safety of avelumab and AVB-S6-500 and see what effects (good and bad) this combination treatment has on ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.4579

Phase Ib study of avelumab and novel AXL inhibitor avb- ... Conclusions: Concurrent avelumab and AVB was safe and AVB effectively neutralized circulating Gas6 across DLs. Albeit small sample size, the ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11988210/

Real-world avelumab first-line maintenance in advanced ... In the meta-analysis, 12-month OS and PFS rates (95% CI) from avelumab 1LM start were 69% (65–73%) and 39% (35–44%), respectively. Conclusion.

4. urotoday.com urotoday.com/clinical-trials/from-the-editor/132430-maintenance-therapy-and-beyond-with-avelumab.html

Maintenance therapy and beyond with avelumab… The primary endpoint was overall survival and this was met with medians of 21.4 (95% CI 18.9-26.1) vs. 14.3 (12.9-17.9) months (HR 0.69; 95% CI ...

5. bavencio.com bavencio.com/en_US/hcp/uc-home/efficacy.html

JAVELIN Bladder Trial Efficacy | BAVENCIO® (avelumab) ... LONG-TERM ANALYSIS (3+ years): Consistent OS results were observed · Long-term OS results in PD-L1–positive patients1,b (n=358, 51% of patients): HR 0.69 (95% CI ...

6. clinicaltrial.be clinicaltrial.be/en/details/5112?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Avelumab in Combination With AVB-S6-500 in Patients ... If the patient is enrolled on the second dose level, the patient will be receive AVB-S6-500 only once a week at a lower dose.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03747419

Avelumab and Radiation in Muscle-Invasive Bladder Cancer Avelumab is currently approved by the FDA for the treatment of metastatic Merckel cell carcinoma (mMCC) and platinum-refractory metastatic urothelial carcinoma.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8882657/

Clinical Evaluation of Avelumab in the Treatment ... Avelumab in recent studies has been found to improve outcomes in patients with locally advanced and metastatic urothelial carcinoma. Patients ...