EG-70 for Bladder Cancer

Recruiting at 60 trial locations

Overseen By enGene clinical trials

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: enGene, Inc.

Must not be taking: Chemotherapy, Pembrolizumab

Disqualifiers: Recent malignancy, Renal failure, Metastatic disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

350 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will evaluate the safety and efficacy of intravesical administration of EG-70 in the bladder and its effect on bladder tumors in patients with NMIBC. This study study consists of two phases; a Phase 1 dose-escalation to establish safety and recommended the phase 2 dose, followed by a Phase 2 study to establish how effective the treatment is. The Study will include patients with NMIBC with Cis for whom BCG therapy is unresponsive and patients with NMIBC with Cis who are BCG-naïve or inadequately treated.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on any concurrent chemotherapeutic agents or have had certain treatments like pembrolizumab within a specified time before screening.

What makes the drug EG-70 unique for treating bladder cancer?

EG-70, also known as Detalimogene Voraplasmid, is unique because it is a gene therapy that uses a plasmid to deliver therapeutic genes directly into bladder cancer cells, potentially offering a novel approach for patients who do not respond to traditional treatments like Bacillus Calmette-Guerin (BCG). This method allows for targeted treatment of cancer cells while minimizing effects on healthy cells. ^{1 2 3 4 5}

Research Team

Christine Tosone, Ms, RAC

Principal Investigator

enGene, Inc.

Eligibility Criteria

This trial is for adults with non-muscle invasive bladder cancer (NMIBC) who haven't responded to BCG therapy or haven't completed it, or are BCG-naïve. They should be able to hold the treatment in their bladder for at least an hour and meet certain health criteria like good liver and kidney function, stable blood counts, no severe infections, and not pregnant. People with a history of certain other medical conditions or treatments are excluded.

Inclusion Criteria

I was treated with a checkpoint inhibitor and it didn't work, but it's been 30 days (Phase 1) or 3 months (Phase 2) since then.

Hepatic inclusion within 2 weeks of Day 1: Total bilirubin must be ≤1.5 x the upper limit of normal (ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN for the institution, alkaline phosphatase ≤2.5 x ULN for the institution, unless bone metastasis is present in the absence of liver metastasis, Adequate renal function with creatinine clearance >30 mL/min, Prothrombin time and partial thromboplastin time within the normal limits at Screening, Must have satisfactory bladder function with ability to retain study drug for a minimum of 60 minutes, Patient or legally authorized representative (LAR) must be willing and able to comply with all protocol requirements, Patient or LAR must be willing and able to give informed consent and any authorizations required by local law for participation in the study

My biopsy for a small tumor was thorough and included the muscle layer.

Exclusion Criteria

I have had issues with urine flowing backward or needed a tube in my urinary tract that hasn't been resolved.

I haven't had cancer treatment or experimental drugs in the last 30 days (or 3 months for certain drugs).

I have ongoing kidney swelling due to a blockage in my urinary tract.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Dose Escalation

Dose escalation to establish safety and recommended Phase 2 dose

12 weeks

Multiple visits for dose escalation and safety monitoring

Phase 2 Treatment

Up to 4 cycles of treatment with EG-70 for eligible patients

48 weeks

Regular visits for treatment and assessments

Maintenance Treatment

Up to 4 maintenance treatment cycles for patients with complete response

48 weeks

Regular visits for maintenance treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 3 years

Periodic follow-up visits

Treatment Details

Interventions

• EG-70

Trial Overview The LEGEND study is testing EG-70 given directly into the bladder to see if it's safe and effective against NMIBC tumors. The trial has two parts: first finding the right dose (Phase 1), then checking how well it works (Phase 2). Participants will either have been unresponsive to prior BCG therapy or never had it.

Participant Groups

Group I: Phase 2 Experimental Treatment 1 Intervention

Cohort 1: Recommended Phase 2 dose (RP2D) with eligible BCG-unresponsive NMIBC patients with CIS, up to 4 cycles of treatment with EG-70 Cohorts 2A, 2B and 3: RP2D with eligible high-risk NMIBC patients with CIS who are BCG-naïve, BCG-exposed (incompletely treated with BCG) or BCG-unresponsive HG Ta/T1 papillary disease without CIS

Group II: Phase 1 Experimental Treatment 1 Intervention

Dose escalation phase

Who Is Running the Clinical Trial?

enGene, Inc.

Lead Sponsor

Trials

1

Recruited

350+

Findings from Research

In a study involving 18 patients with superficial bladder cancer, BC-819 was administered intravesically without any dose-limiting toxicity, indicating it is safe for use in this population.

BC-819 led to a 22% complete response rate in tumor ablation, with 44% of patients achieving either complete ablation or significant reduction of the tumor, suggesting promising preliminary efficacy for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II marker lesion study of intravesical BC-819 DNA plasmid in H19 over expressing superficial bladder cancer refractory to bacillus Calmette-Guerin. Sidi, AA., Ohana, P., Benjamin, S., et al.[2013]

The study successfully constructed a urothelium-specific recombinant adenovirus (Ad-UPII-E1A) that effectively inhibits the growth of bladder cancer cells (BIU-87), demonstrating its potential as a targeted therapy.

The hUPII promoter showed high tissue specificity in bladder cancer cells, which was confirmed through various assays, indicating that this approach could minimize side effects by targeting only cancerous tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Construction of urothelium-specific recombinant adenovirus and its inhibition in bladder cancer cell. He, XD., Wang, ZP., Wei, HY., et al.[2021]

CG0070 is an oncolytic adenovirus that specifically targets and kills cancer cells lacking the retinoblastoma (Rb) protein, making it a promising treatment for certain types of bladder cancer.

The study outlines standardized protocols for administering CG0070 intravesically, providing guidance for its use in patients with bladder cancer that does not respond to traditional BCG therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesical Infusion of Oncolytic Virus CG0070 in the Treatment of Bladder Cancer. Grandi, P., Darilek, A., Moscu, A., et al.[2023]

The EGF-conjugated anthrax toxin effectively targets and induces apoptosis in bladder cancer cells by exploiting their overexpression of EGFR, achieving significant cell death with a low concentration (LC50 < 1 nM) and rapid action (as little as 3 minutes).

In animal studies, this treatment showed no toxicity in tumor-free mice and dogs, and it resulted in an average tumor reduction of ~30% in dogs with spontaneous bladder cancer after just one treatment cycle, highlighting its potential as a safe and effective therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel, safe, fast and efficient treatment for Her2-positive and negative bladder cancer utilizing an EGF-anthrax toxin chimera. Jack, S., Madhivanan, K., Ramadesikan, S., et al.[2023]

Nadofaragene firadenovec (Adstiladrin®) is the first gene therapy approved for bladder cancer, offering a new treatment option for patients who do not respond to Bacillus Calmette-Guérin (BCG) therapy.

Clinical trials have demonstrated high response rates and manageable side effects for nadofaragene firadenovec, indicating its potential as an effective alternative in treating bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interferon gene therapy with nadofaragene firadenovec for bladder cancer: from bench to approval. Martini, A., Tholomier, C., Mokkapati, S., et al.[2023]

References

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

Phase I/II marker lesion study of intravesical BC-819 DNA plasmid in H19 over expressing superficial bladder cancer refractory to bacillus Calmette-Guerin. [2013]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Construction of urothelium-specific recombinant adenovirus and its inhibition in bladder cancer cell. [2021]

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

Intravesical Infusion of Oncolytic Virus CG0070 in the Treatment of Bladder Cancer. [2023]

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

A novel, safe, fast and efficient treatment for Her2-positive and negative bladder cancer utilizing an EGF-anthrax toxin chimera. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Interferon gene therapy with nadofaragene firadenovec for bladder cancer: from bench to approval. [2023]