CG0070 + Nivolumab for Bladder Cancer

Overseen By Austin Lannon

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Immune checkpoint inhibitors, Immunosuppressants

Disqualifiers: Pregnancy, Autoimmune disease, Cardiac diseases, 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)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

21 Participants Needed

Trial Summary

What is the purpose of this trial?

Investigators will evaluate the safety and efficacy of combination neoadjuvant therapy using intravesical CG0070 and IV Nivolumab in cisplatin ineligible patients with Muscle Invasive Bladder Cancer (MIBC).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take immunosuppressive agents within 14 days of starting the study treatment, and certain antiviral medications must be stopped 14 days before and after CG0070 treatment.

What data supports the effectiveness of the drug CG0070 + Nivolumab for bladder cancer?

Nivolumab, a part of the treatment, is an immune-checkpoint inhibitor that has shown significant anti-tumor activity and is approved for use in bladder cancer, especially for patients who have not responded to platinum-based chemotherapy. This suggests that combining it with other treatments like CG0070 could potentially enhance its effectiveness. ^{1 2 3 4 5}

Is the combination of CG0070 and Nivolumab safe for humans?

Nivolumab, an immune checkpoint inhibitor, has been used in various clinical trials for bladder cancer and is generally well-tolerated, with common side effects including fatigue, low blood cell counts, and nausea. While specific safety data for the combination of CG0070 and Nivolumab is not provided, Nivolumab alone has a manageable safety profile in clinical settings. ^{1 6 7 8 9}

What makes the CG0070 + Nivolumab treatment unique for bladder cancer?

The CG0070 + Nivolumab treatment is unique because it combines a viral-based therapy (CG0070) with an immune checkpoint inhibitor (Nivolumab), potentially enhancing the immune system's ability to target and destroy cancer cells. This combination may offer a novel approach compared to traditional chemotherapy or single-agent immunotherapies. ^{1 7 10 11 12}

Research Team

Roger Li, MD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

This trial is for adults with Muscle Invasive Bladder Cancer (MIBC) who can't have cisplatin chemotherapy due to poor kidney function, hearing loss, neuropathy, heart failure or personal choice. They must be fit for certain bladder surgeries and willing to provide tissue samples. Pregnant women, those with serious medical conditions or allergies to the drugs, prior immune therapy use or other active cancers are excluded.

Inclusion Criteria

My bladder cancer is confirmed and falls within specific stages without distant spread.

Criterion: You are unable to receive cisplatin-based chemotherapy due to reasons such as kidney function, hearing or nerve problems, heart failure, or other medical conditions. You must also be eligible for certain surgical procedures, be at least 18 years old, able to understand and sign consent, willing to provide tissue and blood samples, and have certain levels of organ function.

My bladder cancer surgery was within the last 3 months, and there's enough tissue for testing.

Exclusion Criteria

I have bladder cancer symptoms that may prevent me from completing the treatment.

I have been diagnosed with HIV.

Participants with any serious and/or uncontrolled concurrent medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) or psychiatric illness that could, in the investigator's opinion, cause unacceptable safety risks or potentially interfere with the completion of the treatment according to the protocol.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravesical CG0070 (6 instillations) and IV Nivolumab (2 doses) as neoadjuvant therapy

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• CG0070
• Nivolumab

Trial Overview The study tests a combination of CG0070 (a drug put directly into the bladder) and Nivolumab (an IV drug), in patients not eligible for standard chemotherapy. It aims to assess how safe this combo is and how well it works before removing the bladder.

Participant Groups

Group I: Participants Receiving CG0070 & Nivolumab Experimental Treatment 2 Interventions

Both CG0070 (x 6 instillations) and nivolumab (x 2 doses) will be administered at their single-agent dose and schedule.

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

CG Oncology, Inc.

Industry Sponsor

Trials

9

Recruited

900+

Richard M. Shulze Family Foundation

Collaborator

Trials

1

Recruited

20+

Findings from Research

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]

Intravesical immunotherapy with Bacillus Calmette-Guérin remains the standard treatment for non-muscle invasive urothelial bladder cancer (UBC), but recent advances in checkpoint blockade immunotherapy targeting PD-1 and PD-L1 have shown promise for patients with advanced UBC, leading to the FDA approval of five checkpoint inhibitors in the last two years.

The effectiveness of these immunotherapies highlights the importance of understanding the complex interactions between cancer cells and the immune system, as well as the potential for genomic markers to predict patient responses to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unwrapping the genomic characteristics of urothelial bladder cancer and successes with immune checkpoint blockade therapy. Cheng, W., Fu, D., Xu, F., et al.[2020]

In a study of 39 patients with muscle-invasive bladder cancer, the combination of gemcitabine, cisplatin, and the immune checkpoint inhibitor pembrolizumab was effective, achieving pathologic downstaging in 56% of patients and complete pathologic response in 36%.

The treatment was generally safe, with common side effects including thrombocytopenia, anemia, and neutropenia, but no severe immune-related adverse events were reported, indicating a manageable safety profile for this neoadjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Gemcitabine and Split-Dose Cisplatin Plus Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer. Rose, TL., Harrison, MR., Deal, AM., et al.[2022]

Immunotherapy, particularly immune checkpoint inhibitors like atezolizumab and nivolumab, has received accelerated FDA approval for treating metastatic urothelial carcinoma, showing promise in improving patient outcomes.

The use of immunotherapy can lead to unique immune-related adverse events and response patterns, such as pseudoprogression, highlighting the need for careful management and the potential for predictive biomarkers to identify patients who will benefit most from these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy in metastatic urothelial carcinoma: focus on immune checkpoint inhibition. Siefker-Radtke, A., Curti, B.[2021]

In a phase II trial involving 51 patients with muscle-invasive bladder cancer, the combination of nivolumab and gemcitabine/cisplatin (N+GC) was well tolerated and resulted in a clinical complete response in 59% of patients, indicating its potential effectiveness as a neoadjuvant treatment.

The treatment led to a pathologic complete response in 24% of patients overall and 35% among those who underwent radical cystectomy, suggesting that N+GC can achieve significant tumor reduction before surgery, regardless of the patients' PD-L1 expression levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Nivolumab Plus Gemcitabine/Cisplatin Chemotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder. Kim, H., Jeong, BC., Hong, J., et al.[2023]

Avelumab, an antibody targeting PD-L1, showed significant antitumor effects in a bladder cancer model, indicating its potential as an effective treatment for non-muscle invasive urothelial carcinoma.

The study found that the antitumor effects of avelumab were more reliant on CD4 T cells rather than CD8 T cells, suggesting that enhancing the adaptive immune response could improve treatment outcomes for bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Immunotherapy of Non-Muscle Invasive Mouse Bladder Cancer with Avelumab, an Anti-PD-L1 Immune Checkpoint Inhibitor. Vandeveer, AJ., Fallon, JK., Tighe, R., et al.[2021]

Nivolumab, a monoclonal antibody that blocks PD-1, shows a 20% overall response rate in patients with metastatic urothelial carcinoma after failing first-line platinum-based chemotherapy, indicating its potential as a treatment option.

While nivolumab is associated with manageable toxicity, serious immune-related adverse events can occur, and current biomarkers like PD-1/PD-L1 expression are not reliable for predicting patient response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and its use in the second-line treatment of metastatic urothelial cancer. Raggi, D., Necchi, A., Giannatempo, P.[2019]

Nivolumab has received accelerated approval from the FDA for treating patients with locally advanced or metastatic urothelial carcinoma who have experienced disease progression after platinum chemotherapy.

This approval marks the second PD-1-targeting therapy approved for bladder cancer within a year, highlighting the growing options for patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Gets FDA Nod for Bladder Cancer. [2018]

References

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

[Immunotherapy for Bladder Cancer]. [2019]

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

Immunotherapy in Urothelial Cancer: Recent Results and Future Perspectives. [2022]

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

Unwrapping the genomic characteristics of urothelial bladder cancer and successes with immune checkpoint blockade therapy. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Precision Medicine in the Treatment of Locally Advanced or Metastatic Urothelial Cancer: New Molecular Targets and Pharmacological Therapies. [2022]

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

Phase II Study of Gemcitabine and Split-Dose Cisplatin Plus Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Immunotherapy in metastatic urothelial carcinoma: focus on immune checkpoint inhibition. [2021]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors for urothelial carcinoma. [2022]

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

Immune Checkpoint Inhibitors in the Management of Urothelial Carcinoma. [2021]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Neoadjuvant Nivolumab Plus Gemcitabine/Cisplatin Chemotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder. [2023]

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

Systemic Immunotherapy of Non-Muscle Invasive Mouse Bladder Cancer with Avelumab, an Anti-PD-L1 Immune Checkpoint Inhibitor. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Nivolumab and its use in the second-line treatment of metastatic urothelial cancer. [2019]

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

Nivolumab Gets FDA Nod for Bladder Cancer. [2018]