BT8009 for Bladder Cancer

Recruiting in Palo Alto (17 mi)

+166 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: BicycleTx Limited

Must not be taking: CYP3A inhibitors, P-gp inhibitors

Disqualifiers: Active keratitis, High dose corticosteroids, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This is a global, multicenter, randomized, open-label study, with an adaptive design. The main objective of the study is to measure the efficacy and safety of BT8009 (zelenectide pevedotin) as monotherapy and in combination with pembrolizumab in participants with locally advanced or metastatic urothelial cancer (UC). The study includes a dose selection phase followed by an adaptive design continuation. The study is comprised of 2 cohorts. Cohort 1 will include participants who have not received any prior systemic therapy for locally advanced or metastatic UC and are eligible to receive platinum-based chemotherapy, whereas Cohort 2 will include participants who have received ≥ 1 prior systemic therapy for locally advanced or metastatic UC.

Will I have to stop taking my current medications?

The trial requires that participants do not take strong inhibitors or inducers of CYP3A or inhibitors of P-gp while on the study. If you are on such medications, you may need to stop them. Please consult with the trial team for specific guidance.

What data supports the effectiveness of the drug BT8009 for bladder cancer?

Avelumab, a component of the treatment, has shown effectiveness in prolonging overall survival when used as a maintenance therapy after initial chemotherapy in advanced urothelial carcinoma. Additionally, pembrolizumab, another component, is a promising alternative for patients who cannot tolerate cisplatin-based chemotherapy, providing a new option for those with advanced or metastatic urothelial cancer. ^{1 2 3 4 5}

What safety data exists for BT8009 and related treatments in humans?

Avelumab, a treatment related to BT8009, has shown promising safety in patients with advanced bladder cancer, with common side effects including fatigue, low white blood cell count, anemia, muscle pain, decreased appetite, and nausea. These treatments are generally well tolerated, especially for patients who cannot use standard chemotherapy. ^{1 2 3 6 7}

What makes the drug BT8009 for bladder cancer unique?

The drug BT8009 for bladder cancer is unique because it combines multiple agents, including Avelumab, a PD-L1 inhibitor that enhances the immune system's ability to fight cancer, with traditional chemotherapy drugs like Gemcitabine and Cisplatin. This combination aims to improve treatment effectiveness by leveraging both immune system activation and direct cancer cell targeting. ^{1 2 3 4 8}

Research Team

Eligibility Criteria

This trial is for adults with advanced bladder cancer. Cohort 1 includes those who haven't had systemic therapy and can get platinum-based chemo, while Cohort 2 has had at least one systemic treatment. Key eligibility details are not provided.

Inclusion Criteria

Life expectancy ≥ 12 weeks

I am eligible for and have not received platinum-based chemotherapy.

Cohort 1: Participants must not have received prior systemic therapy for locally advanced or metastatic UC with the following exceptions: Prior local intravesical chemotherapy, local surgery when full resection is not achieved, local immunotherapy, and radiotherapy are permitted if completed at least 4 weeks prior to the initiation of study treatment and all acute toxicities have resolved. Prior neoadjuvant/adjuvant chemotherapy or monomethyl auristatin E (MMAE)-based therapy with recurrence >12 months from completion of therapy. Prior neoadjuvant/adjuvant immune checkpoint inhibitor therapy with recurrence >12 months from completion of therapy. Cohort 2: Previously Treated: Participants must have received ≥ 1 prior systemic treatment for locally advanced or metastatic UC. This includes neoadjuvant/adjuvant platinum-based chemotherapy if recurrence occurred within 12 months of completing therapy. Cohort 2: Progression or recurrence of UC during or following receipt of most recent therapy.

Exclusion Criteria

I have fully recovered from any major surgery I had recently.

I have not received a live vaccine in the last 30 days.

Cohort 2: Previously Treated: Received more than 1 prior platinum-based chemotherapy regimen for locally advanced or metastatic UC. This includes neoadjuvant/adjuvant platinum-based chemotherapy if recurrence occurred within 12 months of completing therapy. Cohort 2: Prior treatment with enfortumab vedotin or any other MMAE-based therapy

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Selection

Participants undergo a dose selection phase to determine the appropriate dosage of BT8009

8-12 weeks

Treatment

Participants receive BT8009 as monotherapy or in combination with pembrolizumab

Up to 6 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 7 years

Treatment Details

Interventions

• Avelumab (Monoclonal Antibodies)
• BT8009 (Monoclonal Antibodies)
• Gemcitabine + cisplatin Or carboplatin (Chemotherapy)
• Pembrolizumab (Monoclonal Antibodies)

Trial Overview The study tests BT8009 alone and combined with pembrolizumab against standard chemo (gemcitabine plus cisplatin or carboplatin) in two groups of patients based on prior treatments. It's a global study with an adaptive design to evaluate effectiveness and safety.

Participant Groups

Group I: Cohort 2: BT8009 Arm 2 Experimental Treatment 1 Intervention

Participants will receive BT8009.

Group II: Cohort 2: BT8009 Arm 1 Experimental Treatment 1 Intervention

Participants will receive BT8009.

Group III: Cohort 2: Arm 3: BT8009 (Not Recruiting) Experimental Treatment 2 Interventions

Participants will receive BT8009 and a standard dose of pembrolizumab.

Group IV: Cohort 1: BT8009 Arm 2 Experimental Treatment 2 Interventions

Participants will receive BT8009 and a standard dose of pembrolizumab.

Group V: Cohort 1: BT8009 Arm 1 Experimental Treatment 2 Interventions

Participants will receive BT8009 and a standard dose of pembrolizumab.

Group VI: Cohort 1: Arm 3 Active Control 2 Interventions

Participants will receive Platinum-based combination chemotherapy +/- avelumab maintenance

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Mount Sinai Medical Center of Florida, Inc. Miami Beach, FL

Nebraska Cancer Specialists Omaha, NE

Carolina Urologic Research Center Myrtle Beach, SC

Cancer Specialists of North Florida Jacksonville, FL

More Trial Locations

Who Is Running the Clinical Trial?

BicycleTx Limited

Lead Sponsor

Trials

5

Patients Recruited

1,800+

References

1. 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] The standard treatment in first line of advanced or metastatic urothelial bladder cancer (MBC) is the association of Gemcitabine and Cisplatin (GC). Avelumab, an anti-PD-L1 agent, has recently demonstrated efficacy. The objective is to evaluate the combination of these 3 agents.

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

[Immunotherapy for Bladder Cancer]. [2019] Urothelial carcinoma is the most common urological malignancy. Nonspecific immunotherapy using the Bacillus Calmette-Guerin vaccine has long been the mainstay for the treatment of high-risk superficial bladder carcinoma in an adjuvant setting after transurethral endoscopic resection. In metastatic disease, cisplatin-based chemotherapy remains the main therapeutic modality. In Europe, the standard second-line chemotherapy for patients with cisplatin-refractory tumours is vinflunine. Other systemic treatments with a lower level of evidence include paclitaxel and docetaxel. Studies of tumour microenvironment indicate a significant role for the immune system in the pathogenesis of urothelial tumours and the presence of a CD8 lymphocyte infiltrate is associated with better survival. In urothelial tumours, the correlation between PD-L1 expression in the tumour and the response to PD-1/PD-L1 inhibitors has been repeatedly demonstrated in clinical studies. Several inhibitors of PD-1/PD-L1 pathway are undergoing advanced-phase clinical trials and atezolizumab, nivolumab, pembrolizumab, durvalumab, and avelumab have already have received permanent or temporary registration status in the United States, mostly as second-line treatments for patients progressing on cisplatin-based chemotherapy. Three of these agents are currently registered in Europe: nivolumab for second line treatment and atezolizumab and pembrolizumab for first line treatment in patients not eligible for cisplatin as well as and for second line treatment. These novel immunotherapeutic agents for bladder cancer are relatively well tolerated and therefore potentially useful for patients with contraindications or intolerance to platinum regimens. The main toxicities include asthenia/fatigue, lymphopenia, anaemia, musculoskeletal pain, decreased appetite, and nausea.Key words: bladder cancer - imunotherapy - PD-1 receptor - antibodies - monoclonal This work was supported by the Czech Ministry of Health CR - RVO Thomayer Hospital - TN 0064190. The author declare he has no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 29. 8. 2017Accepted: 3. 10. 2017.

3. Netherlands pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of Pembrolizumab for Patients with Advanced, Unresectable, or Metastatic Urothelial Cancer Ineligible for Cisplatin-based Therapy. [2022] There is an unmet need for effective therapies for patients with advanced or metastatic urothelial cancer who cannot tolerate cisplatin-based chemotherapy. Cisplatin-ineligible patients experience a high frequency of adverse events from the most commonly used standard of care treatment, carboplatin plus gemcitabine, or alternative treatment with gemcitabine monotherapy. Pembrolizumab is a potent, highly selective humanised monoclonal antibody that releases checkpoint inhibition of the immune response system, and provides a new alternative for these patients.

4. 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] Label="BACKGROUND" NlmCategory="BACKGROUND">First-line therapy for treatment of advanced urothelial carcinoma includes combination platinum-based chemotherapies, though resistance and long-term toxicity concerns to these regimens cause limitations in progression-free survival and overall survival. Maintenance treatment with an alternative agent such as the PD-L1 inhibitor, avelumab (Bavencio®), after initial chemotherapy has been shown to prolong overall survival. The aim of this review is to provide a landscape clinical use of avelumab in the treatment of advanced urothelial carcinoma with a focus on patient selection and outcomes.

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

Avelumab as second-line therapy for metastatic, platinum-treated urothelial carcinoma in the phase Ib JAVELIN Solid Tumor study: 2-year updated efficacy and safety analysis. [2021] Anti-programmed cell death ligand 1 (PD-L1)/programmed cell death 1 antibodies have shown clinical activity in platinum-treated metastatic urothelial carcinoma, resulting in regulatory approval of several agents, including avelumab (anti-PD-L1). We report ≥2-year follow-up data for avelumab treatment and exploratory subgroup analyses in patients with urothelial carcinoma.

6. 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] The approval of anti-programmed death ligand 1 (PD-L1) and anti-programmed death 1 agents has expanded treatment options for patients with locally advanced or metastatic urothelial carcinoma. Avelumab, a human monoclonal anti-PD-L1 antibody, has shown promising antitumour activity and safety in this disease. We aimed to assess the safety profile in patients (both post-platinum therapy and cisplatin-naive) treated with avelumab and to assess antitumour activity of this drug in post-platinum patients.

7. England pubmed.ncbi.nlm.nih.gov

First-line avelumab for patients with PD-L1-positive metastatic or locally advanced urothelial cancer who are unfit for cisplatin. [2022] Cisplatin-based chemotherapy is the most recommended treatment for metastatic urothelial cancer (mUC). However, about 50% of patients are considered to be cisplatin ineligible. Anti-programmed cell death protein 1/programmed death-ligand 1 (PD-L1) therapies have, nevertheless, increased the options available to clinicians and are especially valuable for treating these patients. This study therefore tested the activity and safety of avelumab as first-line therapy for mUC.

8. 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] Avelumab (MSB0010718C) is a fully human anti-programmed cell death ligand 1(PD-L1) antibody against PD-L1 interactions and enhances immune activation against tumor cells in the meantime. Avelumab has been approved for locally advanced or metastatic urothelial cancer (mUC) after disease progression in several countries. We therefore conducted this study to evaluate the cost-effectiveness of avelumab maintenance therapy for advanced or mUC from the perspective of the United States (US) and China payer.