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

No longer recruiting at 28 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with advanced bladder cancer that cannot be surgically removed or has recurred or spread. The study tests the safety and early effectiveness of two experimental treatments, INO-5401 and INO-9012, administered with atezolizumab (Tecentriq), a medication that aids the immune system in fighting cancer. Participants are divided into two groups: one for those whose cancer progressed after specific immune therapy and another for those who haven't undergone chemotherapy and cannot receive cisplatin. Suitable candidates have bladder cancer that has worsened despite previous treatment or cannot receive certain standard therapies. As a Phase 1, Phase 2 trial, this study aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that INO-5401 and INO-9012, combined with atezolizumab, are under study for treating bladder cancer. Early studies suggest these treatments might work well together to help the immune system fight cancer. Patients have generally tolerated these treatments well, with common side effects including fatigue and injection site reactions. Serious side effects are rare.

This combination is in early to mid-stage trials, providing some safety information, but more is needed. Atezolizumab is already approved for other uses, offering more known safety data. However, INO-5401 and INO-9012 remain under investigation. Prospective participants should consider that while the combination appears promising, its full safety profile is still being explored. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about INO-5401, INO-9012, and atezolizumab for bladder cancer because they offer a novel approach compared to traditional treatments like cisplatin-based chemotherapy and existing PD-1/PD-L1 inhibitors. Unlike standard treatments, this combination therapy harnesses the power of immunotherapy to boost the body's immune system to better recognize and target cancer cells. INO-5401 and INO-9012 work as DNA-based vaccines that stimulate the immune response, while atezolizumab is an anti-PD-L1 antibody that prevents cancer cells from evading immune detection. This combination could potentially offer a more effective treatment for patients who are ineligible for standard chemotherapy or have shown disease progression despite other immunotherapies.

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

Research has shown that using INO-5401 and INO-9012 with atezolizumab may be very effective against bladder cancer. In this trial, participants in Cohort A and Cohort B will receive this combination treatment. Studies suggest these treatments work together to enhance the immune system's ability to fight cancer cells. Atezolizumab already treats bladder cancer by blocking proteins that prevent the immune system from attacking cancer. INO-5401 and INO-9012 help train the immune system to better identify and combat cancer cells. Early results indicate that this combination could lead to a stronger immune response against cancer. ^{2 3 4 5 6}

Who Is on the Research Team?

Jeffrey Skolnik, MD

Principal Investigator

Inovio Pharmaceuticals

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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, 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, 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03502785

Study Details | NCT03502785 | INO-5401 + INO-9012 in ... 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

2. research-studies.allinforhealth.info research-studies.allinforhealth.info/us/en/listing/1374/an-open-label-multi-center-trial/

An Open-Label Multi-Center Trial of INO-5401 + INO-9012 The purpose of this study is to evaluate safety of the trial treatment, its effects on the immune system and on urothelial cancer.

3. ir.inovio.com ir.inovio.com/news-releases/news-releases-details/2017/Inovio-Pharmaceuticals-Begins-Phase-1b2-Cancer-Efficacy-Trial-Combining-Its-T-cell-Immunotherapy-with-a-PD-L1-Checkpoint-Inhibitor-in-Advanced-Bladder-Cancer/default.aspx

Inovio Pharmaceuticals Begins Phase 1b/2 Cancer Efficacy ... Combining INO-5401/INO-9012 with atezolizumab may provide a synergistic therapeutic effect as a result of generating higher levels of activated ...

4. clinicaltrialsarena.com clinicaltrialsarena.com/news/inovio-studies-ino-5401-ino-9012-phase-ibii-trial-bladder-cancer/

Inovio studies INO-5401 and INO-9012 in Phase Ib/II trial ... The primary aim of the trial is to investigate the benefit of combining a checkpoint inhibitor with a DNA-based immunotherapeutic and T cell ...

5. withpower.com withpower.com/trial/phase-2-carcinoma-transitional-cell-4-2018-c9d73

INO-5401 + INO-9012 + Atezolizumab for Bladder Cancer Atezolizumab, also known as Tecentriq, has been shown to have a favorable safety profile in patients with advanced bladder cancer, with manageable side effects ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03502785

INO-5401 + INO-9012 in Combination With Atezolizumab ... 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 ...