Avelumab + Taxane for Bladder Cancer

Overseen By Rohan Garje, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Yousef Zakharia

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: CNS metastases, Autoimmune disease, Cardiovascular, others

Stay on Your Current Meds You can continue your current medications while participating

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: 9

21 Participants Needed

Trial Summary

What is the purpose of this trial?

This study evaluates the safety and efficacy of the combination of Avelumab, (a fully human anti-programmed death ligand 1 (PD-L1) IgG1 antibody) in combination with a taxane chemotherapy (docetaxel) in patients with metastatic urothelial cancer who are either ineligible to receive cisplatin based chemotherapy, refractory to cisplatin in first line setting or have disease relapse after receiving cisplatin based chemotherapy within a year in the neoadjuvant or adjuvant setting.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on any other anticancer treatments or certain immunosuppressive drugs. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Avelumab + Taxane for bladder cancer?

Research shows that Avelumab, when used as a maintenance treatment after initial chemotherapy, can prolong overall survival in patients with advanced urothelial carcinoma. Additionally, Docetaxel, a type of taxane, has been studied for its effectiveness in treating advanced urothelial cancer, suggesting potential benefits when combined with Avelumab. ^{1 2 3 4 5}

Is the combination of Avelumab and Taxane safe for humans?

Avelumab, used for advanced bladder cancer, is generally well tolerated with side effects like fatigue, low white blood cell count, and nausea. Docetaxel, another component, has been used in various cancers and can cause side effects such as low blood cell counts and fatigue. Both drugs have been studied separately and show a manageable safety profile in humans. ^{2 4 6 7 8}

How is the drug Avelumab + Taxane unique for treating bladder cancer?

Avelumab, a PD-L1 inhibitor, is unique because it enhances the immune system's ability to fight cancer cells and is used as a maintenance therapy after initial chemotherapy to prolong survival in advanced bladder cancer. Combining it with a taxane like Docetaxel, which disrupts cancer cell division, offers a novel approach that targets cancer through both immune activation and direct cell interference. ^{1 5 9 10 11}

Research Team

Yousef Zakharia, MD

Principal Investigator

University of Iowa

Eligibility Criteria

This trial is for adults aged 18-85 with advanced or metastatic urothelial cancer, who can't have cisplatin-based chemo due to health issues or whose cancer has worsened after such treatment. Participants need a certain level of physical fitness and organ function, must not be pregnant, agree to use effective contraception, and cannot have immune conditions or recent major illnesses.

Inclusion Criteria

Biopsy material is required (archival tissue is acceptable if patient could not provide fresh or recent biopsy)

Estimated life expectancy ≥3 months

At least one measurable lesion by RECIST version 1.1

Exclusion Criteria

I am currently receiving treatment for cancer.

I have been treated with drugs that target immune system proteins.

I have not had major surgery in the last 4 weeks or am fully recovered if I did.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose De-escalation

Phase 1b dose de-escalation of Docetaxel in combination with Avelumab to establish the recommended phase 2 dose (RP2D)

9 weeks

3 visits (in-person)

Dose Expansion

Evaluation of the fixed dose of Docetaxel in combination with Avelumab to determine overall response rate (ORR)

18 weeks

6 visits (in-person)

Maintenance

Avelumab administered every 2 weeks until disease progression or toxicity

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Avelumab
• Docetaxel

Trial Overview The AVETAX study tests the combination of Avelumab (an antibody targeting PD-L1) with Docetaxel (a type of chemotherapy), in patients with urothelial cancer that's spread and isn't responding well to standard treatments. The goal is to see if this combo is safe and works better than current options.

Participant Groups

Group I: Avelumab and Docetaxel Experimental Treatment 2 Interventions

Induction phase: Avelumab (10 mg/kg) + Docetaxel (75 mg/m2) every 3 weeks for 6 cycles Maintenance phase: Avelumab (10 mg/kg) every 2 weeks until disease progression or toxicity

Avelumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in United States as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in Japan as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Yousef Zakharia

Lead Sponsor

Trials

5

Recruited

160+

Rohan Garje

Lead Sponsor

Trials

2

Recruited

20+

University of Iowa

Collaborator

Trials

486

Recruited

934,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Findings from Research

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]

In a phase 2 trial involving 22 patients with advanced urothelial cancer who had previously failed platinum-based chemotherapy, the combination of docetaxel and ifosfamide showed an objective response rate of 25%, with 20% achieving complete responses, particularly in those with lymph node-only recurrences.

The treatment was well tolerated, with mild to moderate side effects, and serious toxicities were relatively low, suggesting that this combination therapy could be a viable option for patients with specific recurrence patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel and ifosfamide as second line treatment for patients with advanced or metastatic urothelial cancer after failure of platinum chemotherapy: a phase 2 study. Krege, S., Rembrink, V., Börgermann, C., et al.[2019]

The phase III RANGE study suggests that combining ramucirumab with docetaxel can enhance progression-free survival in patients with advanced or metastatic urothelial carcinoma who have not responded to platinum chemotherapy.

This finding indicates a potential new treatment strategy for a challenging patient population, improving outcomes for those with refractory disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Angiogenesis in Bladder Cancer. [2019]

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]

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]

Avelumab demonstrated antitumor activity in patients with platinum-refractory metastatic urothelial carcinoma, achieving a complete or partial response in 17% of treated patients, including 6% with complete responses.

The safety profile of avelumab was manageable, with most treatment-related adverse events being mild (grade 1-2), although there were serious adverse events in 8% of patients, including one treatment-related death from pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. Patel, MR., Ellerton, J., Infante, JR., et al.[2022]

This phase II study is evaluating the combination of Gemcitabine, Cisplatin, and Avelumab in treating advanced or metastatic bladder cancer, with 90 participants randomized to either the standard treatment or the combination therapy.

The study aims to determine if the addition of Avelumab increases the response rate and duration of response without significantly increasing severe toxicities, with results potentially leading to a larger phase III trial focused on overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label randomized multi-center phase 2 study: gemcitabine cisplatin plus avelumab or gemcitabine cisplatin as first-line treatment of patients with locally advanced or metastatic urothelial bladder carcinoma: GCisAve. Gross-Goupil, M., Domblides, C., Lefort, F., et al.[2022]

Avelumab maintenance therapy is considered cost-effective for treating advanced or metastatic urothelial cancer (mUC) in the United States, with incremental cost-effectiveness ratios (ICERs) of $38,369.50 per QALY for the overall population and $16,150.29 per QALY for the PD-L1-positive population.

In contrast, avelumab was not deemed cost-effective in China, with ICERs of $241,610.25 and $100,528.29 per QALY for the overall and PD-L1-positive populations, respectively, exceeding the local willingness to pay threshold.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Avelumab Maintenance Therapy Plus Best Supportive Care vs. Best Supportive Care Alone for Advanced or Metastatic Urothelial Carcinoma. Xie, Q., Zheng, H., Chen, Y., et al.[2022]

References

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

Clinical Evaluation of Avelumab in the Treatment of Advanced Urothelial Carcinoma: Focus on Patient Selection and Outcomes. [2022]

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

Docetaxel and ifosfamide as second line treatment for patients with advanced or metastatic urothelial cancer after failure of platinum chemotherapy: a phase 2 study. [2019]

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

Targeting Angiogenesis in Bladder Cancer. [2019]

4. England pubmed.ncbi.nlm.nih.gov

The JAVELIN Bladder Medley trial: avelumab-based combinations as first-line maintenance in advanced urothelial carcinoma. [2023]

5. England pubmed.ncbi.nlm.nih.gov

A review of avelumab in locally advanced and metastatic bladder cancer. [2020]

6. Czech Republic pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. [2019]

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

Treatment of patients with metastatic urothelial carcinoma and impaired renal function with single-agent docetaxel. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. [2022]

9. France pubmed.ncbi.nlm.nih.gov

Open-label randomized multi-center phase 2 study: gemcitabine cisplatin plus avelumab or gemcitabine cisplatin as first-line treatment of patients with locally advanced or metastatic urothelial bladder carcinoma: GCisAve. [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

Avelumab first-line maintenance plus best supportive care (BSC) vs BSC alone for advanced urothelial carcinoma: JAVELIN Bladder 100 Japanese subgroup analysis. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Avelumab Maintenance Therapy Plus Best Supportive Care vs. Best Supportive Care Alone for Advanced or Metastatic Urothelial Carcinoma. [2022]