Copanlisib + Avelumab for Advanced Bladder Cancer

Overseen By Hizra Farrukh, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: VA Office of Research and Development

Must be taking: Avelumab

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: CNS metastases, Autoimmune disease, Cardiovascular disease, others

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

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

Compensation: Varies

Number of Visits: 2

Duration: 104 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for individuals with advanced bladder cancer that has spread to other parts of the body. Researchers aim to determine if combining a standard immunotherapy drug, avelumab, with a study drug, copanlisib (a type of targeted therapy), can prevent cancer progression after initial chemotherapy. Participants should have bladder cancer that hasn't progressed after completing chemotherapy and should be suitable for ongoing immunotherapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you should not be on immunosuppressive medication within 7 days prior to the trial, except for certain types like inhaled or topical steroids. 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?

In a previous study, researchers examined the safety of using copanlisib with avelumab to treat advanced bladder cancer. Both treatments are administered through an IV, delivering the medicine directly into the bloodstream.

Avelumab has FDA approval for certain cancers, and research shows it is generally well-tolerated. Common side effects include fatigue and infusion reactions, which are usually mild and manageable.

Copanlisib is still under safety evaluation. Previous patients experienced side effects like high blood sugar and high blood pressure, but these can often be controlled with medication.

Overall, studies suggest that while both drugs have side effects, they are generally manageable. It is important to consult a doctor to understand how these might affect an individual. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of copanlisib and avelumab for advanced bladder cancer because it brings a novel approach to treatment. Unlike traditional therapies that often revolve around chemotherapy, avelumab is an immunotherapy that helps the immune system recognize and attack cancer cells. Copanlisib adds a unique angle by inhibiting specific enzymes (PI3K inhibitors) that help cancer cells grow. Combining these two could potentially offer a more effective way to control the cancer by both boosting the body's immune response and directly targeting cancer cell growth pathways.

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

Research shows that combining copanlisib and avelumab may offer a promising maintenance treatment for advanced bladder cancer. In this trial, participants will receive both drugs. The JAVELIN Bladder 100 study demonstrated that avelumab helps patients with advanced bladder cancer live longer after chemotherapy. Researchers are testing copanlisib to see if it can enhance this effect. This combination uses avelumab to boost the immune system and copanlisib to inhibit cancer cell growth. The goal is to prevent cancer from worsening after initial chemotherapy. ^{1 2 4 6 7}

Who Is on the Research Team?

Chong-Xian Pan, MD PhD

Principal Investigator

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Are You a Good Fit for This Trial?

Adults over 18 with advanced bladder cancer who've finished first-line platinum-based chemo without disease progression are eligible. They must have a life expectancy of at least 3 months, controlled diabetes (A1c < 8.5%), and be able to perform daily activities with some limitations (ECOG PS ≤2 or Karnofsky ≥60%). Exclusions include recent major surgery, other cancer treatments within the last month, certain prior therapies for bladder cancer, active infections like HIV/HBV/HCV, severe allergies to monoclonal antibodies, and uncontrolled medical conditions.

Inclusion Criteria

Patients must have had X-rays, CT/ MRI scans, PET or physical examinations completed within 28 days prior to initial administration of study medications

Estimated life expectancy of at least 3 months

I finished my first round of platinum-based chemotherapy between 4 and 10 weeks ago.

Exclusion Criteria

I have an autoimmune disease that could worsen with immune-boosting treatments.

I am HIV positive or have AIDS.

You have serious ongoing health problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Patients with advanced urothelial cancer are treated with platinum-based chemotherapy to assess cancer response

8-12 weeks

Treatment

Participants receive avelumab and copanlisib as maintenance therapy through intravenous infusion

104 weeks

Avelumab every 2 weeks, Copanlisib on Day 1, 8, and 15 of each 4-week cycle

Follow-up

Participants are monitored for disease progression and adverse events

up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Avelumab
• Copanlisib

Trial Overview This trial tests copanlisib in combination with standard immunotherapy drug avelumab as maintenance therapy for patients whose metastatic bladder cancer hasn't progressed after chemotherapy. The goal is to see if this combo can help keep the cancer from advancing further.

How Is the Trial Designed?

Group I: Therapeutic arm Experimental Treatment 2 Interventions

Copanlisib will be administered through intravenous infusion (IV) at 60 mg on Day 1, 8 and 15, and avelumab will be administered 800 mg IV on Day 1 and 15 of each 4-week treatment cycle for up to 26 cycles

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Published Research Related to This Trial

Avelumab maintenance therapy after platinum-based chemotherapy in advanced urothelial carcinoma significantly improves overall response rate (ORR), progression-free survival (PFS), and overall survival (OS), especially in patients with PD-L1 positive tumors, compared to those receiving best supportive care.

While avelumab is effective, it is associated with a high rate of treatment-related adverse events (TRAEs) in 86.7% of patients, with 32.4% experiencing severe adverse events, indicating the need for careful patient monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Evaluation of Avelumab in the Treatment of Advanced Urothelial Carcinoma: Focus on Patient Selection and Outcomes. Ten Eyck, JE., Kahlon, N., Masih, S., et al.[2022]

Avelumab, an anti-PD-L1 antibody, has received FDA accelerated approval for treating recurrent or metastatic urothelial carcinoma after first-line chemotherapy failure, highlighting its role in improving survival for patients with this aggressive cancer.

This approval marks a significant advancement in immunotherapy for urothelial carcinoma, as it is the fifth immune checkpoint inhibitor approved for this condition, indicating a growing recognition of the efficacy of immune checkpoint blockade in managing advanced bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of avelumab in locally advanced and metastatic bladder cancer. Rao, A., Patel, MR.[2020]

Atezolizumab, a PD-L1 inhibitor, has shown effectiveness as a first-line treatment for advanced bladder cancer in patients who cannot receive standard cisplatin chemotherapy, according to a phase II study.

Nearly 25% of the patients in the study experienced durable responses to atezolizumab, highlighting its potential as a viable treatment option for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Atezolizumab Effective in Bladder Cancer. [2019]

Urothelial carcinoma, the most common urological cancer, is primarily treated with Bacillus Calmette-Guerin (BCG) immunotherapy for superficial cases and cisplatin-based chemotherapy for metastatic disease, with vinflunine as the standard second-line option in Europe.

Novel PD-1/PD-L1 inhibitors like atezolizumab, nivolumab, and pembrolizumab have shown promise in treating bladder cancer, particularly for patients who cannot tolerate cisplatin, and are generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. Büchler, T.[2019]

Recent advancements in immunotherapy, particularly immune-checkpoint inhibitors like atezolizumab and pembrolizumab, have shown significant anti-tumor activity and improved survival rates in patients with advanced urothelial carcinoma who have previously failed platinum-based chemotherapy.

These immune-checkpoint inhibitors have tolerable safety profiles and have been FDA-approved for use in bladder cancer, marking a shift in treatment standards and offering hope for better long-term outcomes compared to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy in Urothelial Cancer: Recent Results and Future Perspectives. Farina, MS., Lundgren, KT., Bellmunt, J.[2022]

Pembrolizumab significantly improves survival and quality of life for patients with advanced urothelial cancer who cannot tolerate cisplatin-based chemotherapy, offering an increase of approximately 2.11 to 2.16 years in overall survival and 1.71 to 1.75 quality-adjusted life years (QALYs) compared to standard treatments like carboplatin plus gemcitabine and gemcitabine monotherapy.

Despite being associated with higher costs (an increase of €90,520 compared to carboplatin plus gemcitabine), pembrolizumab is considered cost-effective at a threshold of €100,000/QALY, making it a viable first-line treatment option for this patient population in Sweden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of Pembrolizumab for Patients with Advanced, Unresectable, or Metastatic Urothelial Cancer Ineligible for Cisplatin-based Therapy. Patterson, K., Prabhu, V., Xu, R., et al.[2022]

Avelumab, a PD-L1 inhibitor, has been established as a new standard of care for patients with advanced or metastatic urothelial carcinoma (UC) following platinum-based chemotherapy, based on results from the JAVELIN bladder 100 trial.

The use of maintenance avelumab after initial chemotherapy has shown promise in restoring T cell responses against tumors, indicating a potential improvement in treatment outcomes for UC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab in locally advanced or metastatic urothelial carcinoma. Jackson-Spence, F., Szabados, B., Toms, C., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05687721

Study Details | NCT05687721 | Copanlisib and Avelumab ... A Phase II Trial With Copanlisib Plus Avelumab as a Maintenance Therapy for Metastatic Bladder Cancer After Platinum-based Chemotherapy

2. asco.org asco.org/abstracts-presentations/ABSTRACT416206

A phase II trial with copanlisib plus avelumab as ... A phase II trial with copanlisib plus avelumab as maintenance therapy for metastatic bladder cancer after platinum-based chemotherapy. · Similar Abstracts.

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

Clinical Evaluation of Avelumab in the Treatment ... Avelumab as a maintenance therapy after platinum-based chemotherapy failure or in platinum-ineligible patients with advanced or metastatic urothelial carcinoma ...

4. emdserono.com emdserono.com/us-en/company/news/press-releases/new-analyses-reinforce-survival-benefit-of-bavencio-first-line-maintenance-treatment-in-patients-with-advanced-urothelial-carcinoma-13-02-2023.html

New Analyses Reinforce Survival Benefit of BAVENCIO “Based on the significant improvement in overall survival demonstrated in the Phase III JAVELIN Bladder 100 study, platinum-based chemotherapy ...

5. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT05687721?keyword=%22Urinary%20Bladder%20Neoplasms%22

San Mateo Clinical Trial Copanlisib and Avelumab as a ... Both medications are administrated through intravenous infusion. Avelumab wil be given once every two weeks while copanlisib will be administrated on Day 1, 8 ...

6. dana-farber.org dana-farber.org/clinical-trials/18-464

A Phase 2 Study of Avelumab in Combination with Bladder ... This research study is studying the effects of adding a certain type of immunotherapy to standard bladder-directed radiation as a treatment for muscle-invasive ...

7. bavencio.com bavencio.com/en_US/patients-and-caregivers/uc-home/clinical-study-results.html

Clinical Study Results See how BAVENCIO (avelumab) was studied as a maintenance treatment in certain patients with advanced urothelial carcinoma (UC).