EG-70 for Bladder Cancer

Recruiting at 128 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called EG-70 (Detalimogene Voraplasmid) for bladder cancer. The goal is to determine its safety and effectiveness for individuals with non-muscle invasive bladder cancer (NMIBC) that hasn't responded well to the common treatment, BCG. Participants include those whose bladder cancer BCG couldn't treat successfully or who haven't fully tried BCG yet. For those dealing with bladder cancer unresponsive to usual treatments and not considering surgery, this trial might be suitable. As a Phase 1, Phase 2 trial, it focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that EG-70 is likely to be safe for humans?

Research shows that EG-70, a new gene therapy for bladder cancer, is being tested for safety and patient tolerance. In earlier studies, researchers administered EG-70 directly into the bladder to help the immune system fight cancer cells. These studies found that many patients tolerated the treatment well. Some side effects, such as mild bladder irritation and urinary symptoms, were reported but generally remained manageable.

The treatment is still in early testing stages, so researchers are collecting more safety information. However, reaching this stage suggests it has shown promise in terms of safety so far. While these results are encouraging, more data will provide a fuller understanding of EG-70's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bladder cancer?

Most treatments for bladder cancer involve immunotherapy with Bacillus Calmette-Guérin (BCG), which is a type of bacteria used to stimulate the immune system. However, EG-70 stands out because it is a non-viral gene therapy designed to stimulate the body's immune response differently. Unlike traditional BCG treatment, EG-70 directly targets and enhances the immune system's ability to fight cancer cells by introducing new genetic material. Researchers are excited about EG-70 because it could offer a new avenue for patients who are unresponsive to BCG, potentially providing a more effective option for those with high-risk non-muscle invasive bladder cancer.

What evidence suggests that EG-70 might be an effective treatment for bladder cancer?

Research has shown that EG-70, a new gene therapy, could be promising for treating bladder cancer. In earlier studies, EG-70 helped 71% of patients with a type of bladder cancer that didn't respond to BCG therapy achieve a complete response. This trial will evaluate EG-70 in different phases: Phase 1 involves dose escalation, while Phase 2 includes various cohorts of patients with BCG-unresponsive or high-risk non-muscle invasive bladder cancer (NMIBC). EG-70 delivers genes directly into bladder cells, potentially enhancing the body's ability to fight cancer. Early results are encouraging and suggest it might help shrink or eliminate bladder tumors. ^{2 3 5 6 7}

Who Is on the Research Team?

Christine Tosone, Ms, RAC

Principal Investigator

enGene, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.802

A phase 2 study of detalimogene voraplasmid (EG-70) ... A phase 2 study of detalimogene voraplasmid (EG-70), a novel, non-viral intravesical gene therapy for patients with BCG-unresponsive non-muscle invasive ...

2. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-bladder-cancer/158229-asco-gu-2025-preliminary-results-from-legend-a-phase-2-study-of-detalimogene-voraplasmid-eg-70-a-novel-non-viral-intravesical-gene-therapy-for-patients-with-bcg-unresponsive-nmibc-with-cis.html

A Phase 2 Study of Detalimogene Voraplasmid (EG-70) ... A phase 2 study of detalimogene voraplasmid (EG-70) for patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with CIS.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1078143924009001

117 mechanism of action and translation to the clinic of ... Detalimogene voraplasmid (formerly known as EG-70) is a novel, investigational, non-integrating, non-viral gene therapy that was specifically designed to elicit ...

4. auajournals.org auajournals.org/doi/10.1097/01.JU.0001015816.87470.c9.08

P2-08 LEGEND: A PHASE 1/2 STUDY OF EG-70 ... A first-in-human, phase 1/2, open-label, multicenter study of EG-70 in patients with high-risk BCG-unresponsive NMIBC with carcinoma in situ (CIS).

5. onclive.com onclive.com/view/preliminary-data-demonstrate-high-cr-rate-with-detalimogene-in-bcg-unresponsive-nmibc-with-cis

Preliminary Data Demonstrate High CR Rate With ... Detalimogene voraplasmid generated a 71% complete response rate in patients with BCG-unresponsive non–muscle invasive bladder cancer and CIS.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS4631

LEGEND: A phase 1/2 study of detalimogene voraplasmid ... A phase 1/2 study of detalimogene voraplasmid (EG-70), an intravesical monotherapy for patients with high-risk non–muscle-invasive bladder cancer (NMIBC).

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03628-7/fulltext

2023TiP A phase I/II study of EG-70 (detalimogene ... EG-70 is an investigational, intravesically administered therapy designed to elicit local stimulation of anti-tumor immune responses in the bladder and drive ...