INO-5401 + INO-9012 + Atezolizumab for Bladder Cancer

Recruiting at 27 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Inovio Pharmaceuticals

Must not be taking: Chemotherapy, Immunostimulatory, Immunosuppressive, others

Disqualifiers: CNS metastases, Autoimmune disease, HIV, 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: Unknown

Duration: 12 weeks

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase I/IIA, open-label, multi-center trial to evaluate the safety, immunogenicity and preliminary clinical efficacy of INO-5401 + INO-9012 delivered by intramuscular (IM) injection followed by electroporation (EP), in combination with atezolizumab in participants with locally advanced unresectable or metastatic/recurrent Urothelial Carcinoma (UCa). The trial population is divided into two cohorts: Cohort A: Participants with locally advanced unresectable or metastatic/recurrent UCa, who have confirmed disease progression during or following treatment with anti-Programmed Death receptor-1/Programmed Death receptor Ligand-1 (anti-PD-1/PD-L1) therapy; Cohort B: Participants with locally advanced unresectable or metastatic/recurrent UCa, who are treatment naïve and ineligible for cisplatin-based chemotherapy. A safety run-in will be performed with up to six participants (safety analysis participants) from cohort A.

Will I have to stop taking my current medications?

The trial requires that you stop any approved anti-cancer therapy, including chemotherapy, targeted therapy, or radiation therapy, at least 2 weeks before starting the trial. If you are on systemic immunostimulatory or immunosuppressive medications, you may also need to stop those.

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

Atezolizumab has been shown to be effective for advanced bladder cancer, with a 15% response rate in patients whose cancer progressed after first-line chemotherapy and a 24% response rate in those who were chemotherapy-naïve and ineligible for cisplatin. It has been approved by the FDA for use in these cases, demonstrating better response rates and survival compared to other treatments. ^{1 2 3 4 5}

Is the combination of INO-5401, INO-9012, and Atezolizumab safe for humans?

Atezolizumab, also known as Tecentriq, has been shown to have a favorable safety profile in patients with advanced bladder cancer, with manageable side effects and a lower rate of severe adverse events compared to traditional chemotherapy. ^{1 2 3 6 7}

How is the drug combination of INO-5401, INO-9012, and Atezolizumab unique for bladder cancer treatment?

This drug combination is unique because it includes Atezolizumab, a monoclonal antibody that blocks PD-L1 to enhance the immune system's ability to fight cancer, and is combined with INO-5401 and INO-9012, which are designed to stimulate the immune system further. This approach aims to improve immune response against bladder cancer, offering a novel strategy compared to traditional chemotherapy. ^{1 2 3 6 7}

Research Team

Jeffrey Skolnik, MD

Principal Investigator

Inovio Pharmaceuticals

Eligibility Criteria

This trial is for adults with advanced bladder cancer that's either come back or can't be removed by surgery. Cohort A must have worsened on anti-PD-1/PD-L1 therapy, while Cohort B are those who haven't had chemo and can't take cisplatin. Participants need to be fairly healthy, able to provide a tissue sample, and not planning to conceive.

Inclusion Criteria

Have a performance status of 0 or 1 on Eastern Cooperative Oncology Group (ECOG) Performance Scale

For Cohort A: Subjects who have radiographically confirmed disease progression during or following treatment with an anti-PD-1/PD-L1 based therapy

Be willing to provide a tissue sample for pre-treatment intra-tumoral assessment of proinflammatory and immunosuppressive factors

Exclusion Criteria

Active hepatitis B or active hepatitis C

You had other types of cancer within the past 3 years, except for certain types that have a low risk of spreading and were successfully treated.

Treatment with systemic immunosuppressive medication

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

A safety run-in will be performed with up to six participants from cohort A to evaluate safety and tolerability

4 weeks

Treatment

Participants receive INO-5401 and INO-9012 in combination with atezolizumab

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Treatment Details

Interventions

• Atezolizumab
• Electroporation
• INO-5401
• INO-9012

Trial Overview The study tests INO-5401 + INO-9012 (DNA plasmids) given via injection followed by electroporation, combined with the immunotherapy drug Atezolizumab. It aims to see if this mix boosts the immune system against bladder cancer cells in patients previously treated and new patients unfit for standard chemo.

Participant Groups

Group I: Cohort B Experimental Treatment 4 Interventions

Participants with locally advanced unresectable or metastatic/recurrent UCa who are treatment naïve and ineligible for cisplatin-based chemotherapy. Cohort B participants will be treated with INO-5401 and INO-9012 in combination with atezolizumab.

Group II: Cohort A Experimental Treatment 4 Interventions

Participants with locally advanced unresectable or metastatic/recurrent UCa, who have confirmed disease progression during or following treatment with an anti-PD-1/PD-L1 therapy. Cohort A participants will be treated with INO-5401 and INO-9012 in combination with atezolizumab.

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

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Inovio Pharmaceuticals

Lead Sponsor

Trials

54

Recruited

4,800+

Findings from Research

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

Atezolizumab, a monoclonal antibody targeting PD-L1, showed a 23% response rate and a median overall survival of 15.9 months in 119 patients with metastatic urothelial cancer who were unfit for cisplatin, indicating its efficacy as a front-line treatment.

In patients whose tumors progressed after first-line chemotherapy, atezolizumab had a 15% response rate and a median overall survival of 7.9 months, with better outcomes (26% response rate) in those with high PD-L1 expression, demonstrating its potential effectiveness based on biomarker status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. Bernard-Tessier, A., Bonnet, C., Lavaud, P., et al.[2019]

Atezolizumab, an anti-PD-L1 therapy, showed long-term safety and efficacy in patients with metastatic urothelial carcinoma, with a median follow-up of 37.8 months and a low incidence of severe treatment-related adverse events (9%).

The treatment resulted in a 26% objective response rate, with a median duration of response of 22.1 months, and median overall survival of 10.1 months, particularly benefiting patients with higher PD-L1 expression on immune cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab (MPDL3280A) Monotherapy for Patients With Metastatic Urothelial Cancer: Long-term Outcomes From a Phase 1 Study. Petrylak, DP., Powles, T., Bellmunt, J., et al.[2022]

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]

In a study of 115 patients with metastatic urothelial carcinoma treated with atezolizumab (ATZ) after failing first-line chemotherapy, the objective response rate was 28.7%, indicating that ATZ is effective in this patient population.

The treatment was well tolerated, with 98% of patients experiencing adverse events, but only 21.2% had severe (grade 3-4) treatment-related adverse events, suggesting a manageable safety profile similar to previous clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences. Tural, D., Ölmez, ÖF., Sümbül, AT., et al.[2022]

Atezolizumab, an anti-PD-L1 monoclonal antibody, has shown durable responses in treating locally advanced and metastatic urothelial cancer, especially in patients who have failed platinum-based chemotherapy or are ineligible for cisplatin.

The treatment with atezolizumab has a more favorable toxicity profile compared to traditional cytotoxic chemotherapy, making it a promising option for patients with advanced bladder cancer, although further research is needed to identify additional predictive markers for response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab in invasive and metastatic urothelial carcinoma. Crist, M., Balar, A.[2019]

References

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

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

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

Atezolizumab: First Global Approval. [2019]

3. France pubmed.ncbi.nlm.nih.gov

[Atezolizumab (Tecentriq®): Activity, indication and modality of use in advanced or metastatic urinary bladder carcinoma]. [2019]

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

Atezolizumab (MPDL3280A) Monotherapy for Patients With Metastatic Urothelial Cancer: Long-term Outcomes From a Phase 1 Study. [2022]

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

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

6. Netherlands pubmed.ncbi.nlm.nih.gov

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences. [2022]

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

Atezolizumab in invasive and metastatic urothelial carcinoma. [2019]