A Phase 1/2 Study of EG-70 as an Intravesical Administration to Patients With BCG Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC) and High-Risk NMIBC Patients Who Are BCG Naïve or Received Incomplete BCG Treatment

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Engene Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Jan 2025 → ongoing

Decision date (initial)

2024-12-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

enGene Inc.

External identifiers

EU CT number

2024-512900-20-00

ClinicalTrials.gov

NCT04752722

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate efficacy of EG 70 (determined by complete response [CR]) at any time in each cohort separately (for NMIBC with CIS cohorts).

Secondary objectives 4

1. To evaluate the safety of the RP2D of EG 70 administered by intravesical instillation in patients with BCG-unresponsive NMIBC and patients with high-risk NMIBC who are BCG- naïve or have received incomplete BCG treatment.
2. To evaluate efficacy of EG 70 determined by CR at the efficacy analysis following each cycle and the duration of CR in each cohort separately (for NMIBC cohorts with CIS).
3. To evaluate efficacy of EG 70 determined by disease-free survival in the NMIBC papillary-only cohort (Cohort 3).
4. To evaluate Quality of Life Assessment in each cohort separately.

Conditions and MedDRA coding

Non-muscle invasive bladder cancer (NMIBC)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. 1.BCG-unresponsive NMIBC with CIS of the bladder, with or without coexisting papillary Ta/T1 tumor(s) who are ineligible for or have elected not to undergo cystectomy at the time of enrollment, and have experienced CIS disease within 12 months of treatment, where: • Adequate BCG regimen consists of at least 2 courses of BCG where the first course (induction) must have included at least 5 of 6 doses and the second course may have included a reinduction (at least 2 of 6 treatments) or maintenance (at least 2 of 3 doses). In addition, the qualifying course of BCG must have consisted of full dose BCG (i.e., 50 mg per dose): at least 5 of the 6 doses of the first course (induction) must be full dose BCG and at least 2 doses of the second course (maintenance or reinduction) must be full dose BCG. Adequacy of the BCG regimen to be reviewed determined by the Investigator in conjunction with the Sponsor. Notes: -In patients receiving a second induction course of BCG, this second induction course should ideally follow the first induction course within 6 months of completion of the first course of BCG. Additionally, there should ideally be no disease free interval between the first induction BCG course and the second BCG, and patients should not have received non-BCG therapies (e.g., intravesical gemcitabine). -In patients receiving a maintenance course of BCG, the maintenance course should ideally follow the induction course within 6 months and can have a disease-free interval. However, patients should NOT have received any intervening intravesical therapies (e.g., intravesical gemcitabine). -Completion of qualifying BCG treatment (e.g., “5+2” minimum exposure) within 12 months of the initial qualifying dose of BCG (e.g., induction and initial maintenance or reinduction cycle must be completed within approximately 12 months, with Sponsor review). • Patients with BCG-unresponsive NMIBC may have received subsequent approved treatment for NMIBC (i.e., other than BCG) for NMIBC that was discontinued prior to the Screening biopsy. • CIS must be documented or indicated by pathology at Screening or within 4 months of Screening (provided no therapy for CIS disease was given after the most recent biopsy). • Prior to enrollment, all patients should have TURBT of all visible papillary tumors.
2. 2.Phase 2, Other than Cohort 1: Inclusion for Cohorts 2A, 2B, OR 3: Patient is to meet inclusion of Cohort 2A (BCG-naïve NMIBC with CIS),Cohort 2B (BCG exposed NMIBC with CIS),or Cohort 3 (BCG-unresponsive, HG Ta/T1 papillary disease without CIS), where:Patients are ineligible for or have elected not to undergo cystectomy at the time of enrollment. Cohort 2A (BCG-naïve NMIBC with CIS) OR Cohort 2B (BCG-exposed NMIBC with CIS): NMIBC with current CIS of the bladder, with or without coexisting papillary Ta/T1 NMIBC tumor(s),who are ineligible for or have elected not to undergo cystectomy where: • Either: 2A) BCG-naïve: no previous treatment with BCG or treatment with intravesical BCG > 5 years prior to enrollment but may be allowed to have received a single dose of intravesical chemotherapy at the time of TURBT (perioperative) or who may have received a course of prior intravesical chemotherapy after TURBT. Where: -patients are in countries/ regions impacted by BCG shortages or unavailability, or - patients may have exhausted Standard of Care (SoC) options, may be intolerant to, or have been offered and refused, SoC, or the patient’s treating physician considers that the lack of SoC treatment is not detrimental for the patient (and where patient consents to investigational medicinal product study). • Or 2B) BCG-exposed: includes incomplete BCG treatment (at least 1 dose and less than 5+2 doses required for adequate dosing per Cohort 1, and/or timing of relapse > 12 months and ≤ 5 years. For example, this includes delayed relapse after adequate or inadequate BCG treatment where > 12 months and ≤ 5 years have elapsed. This cohort also includes patients who received ≥ 1 partial dose of BCG (i.e., < 50 mg) as part of their qualifying course of BCG. •Approved treatment for NMIBC must have been discontinued prior to the Screening biopsy. •CIS must be documented or indicated by pathology within 4 months of or at Screening (without subsequent CIS treatment). •Prior to enrollment, all patients should have TURBT of all visible papillary tumors. OR Cohort 3: BCG-unresponsive HG Ta/T1 papillary disease without CIS, where: • Ta/T1 tumor(s) who are ineligible for or have elected not to undergo cystectomy at the time of enrollment and have experienced disease within 12 months of BCG treatment. • Adequate BCG regimen consists of at least 2 courses of BCG where the first course (induction) must have included at least 5 of 6 doses and the second course may have included a reinduction (at least 2 of 6 treatments) or maintenance (at least 2 of 3 doses). •Patients with BCG-unresponsive NMIBC may have received subsequent approved treatment for NMIBC that discontinued prior to the Screening biopsy. • Absence of CIS must be documented or indicated by pathology at Screening or within 4 months of Screening (provided no therapy for HG disease was given after the most recent biopsy). • Prior to enrollment, all patients should have TURBT of all visible papillary tumors.
3. 3. Patients who have previously been treated with an investigational or approved checkpoint inhibitor (e.g., pembrolizumab) are eligible for inclusion 30 days post-treatment (Phase 1) or 43 months post-treatment (Phase 2).
4. 4. Male or non-pregnant, non-lactating female, 18 years or older.
5. 5.Women of child-bearing potential must have a negative pregnancy test at Screening.
6. 6. Female patients of child-bearing potential must be willing to consent to using highly effective birth control methods while on treatment and for 3 months (6 months in France) after their participation in the study ends; male patients are required to utilize a condom for the duration of the study treatment through 3 months post-dose.
7. 7. In Phase 2, for patients with T1 lesions for Cohort 1 or Cohort 2 (CIS + T1) or Cohort 3 (T1), patients with HG T1 may be eligible after repeat-TURBT (ideally within 4 weeks of first TURBT) if the repeat pathology shows non-invasive (Ta or less) or no disease. Repeat TURBT must confirm that muscularis propria is present and uninvolved in the specimen. TURBT to occur within 4 months of Screening
8. 8. Performance Status: Eastern Cooperative Oncology Group 0, 1, and 2.
9. 9. Hematologic inclusion at Screening: • Absolute neutrophil count >1,500/mm3. • Hemoglobin >9.0 g/dL. • Platelet count >100,000/mm3.
10. 10. Hepatic inclusion at Screening: • Total bilirubin must be ≤1.5 x the upper limit of normal (ULN). • Aspartate aminotransferase and alanine aminotransferase ≤2.5 x ULN, and alkaline phosphatase ≤2.5 x ULN.
11. 11. Adequate renal function with creatinine clearance >30 mL/min.
12. 12. Prothrombin time and partial thromboplastin time 1.25 x ULN at Screening or within the therapeutic range if on anticoagulation therapy.
13. 13. Must have satisfactory bladder function with ability to retain study drug for a minimum of 60 minutes.
14. 14. Patient or legally authorized representative (LAR) must be willing and able to comply with all protocol requirements.
15. 15. Patient or LAR must be willing and able to give informed consent and any authorizations required by local law for participation in the study.
16. 16. All specimens must be predominantly urothelial (transitional cell) and have less than 10% variant (e.g., sarcomatoid, squamous component) histology.

Exclusion criteria 23

1. 1. Active malignancies (i.e., progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. Potential allowed exceptions include indolent or definitively treated disease not expected to require treatment during the study. Others may be allowed under Sponsor approval. Examples of potential allowed exceptions include: • Skin cancer (non-melanoma or melanoma) that is considered to be cured. • Non-invasive cervical cancer that is considered to be cured. • Adequately treated lobular CIS and ductal CIS. • History of localized breast cancer and receiving antihormonal agents. • Localized prostate cancer (N0M0): - With a Gleason score of 6, treated within the last 24 months or untreated and under surveillance, - With a Gleason score of 3+4 that has been treated more than 6 months prior to full study Screening and considered to have a very low risk of recurrence, or - With a history of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence.
2. 18. Active interstitial cystitis on cystoscopy or biopsy.
3. 19. Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
4. 2. Has had urothelial carcinoma outside of the urinary bladder (i.e., urethra, ureter, or renal pelvis), that is stage T2 or higher, Ta/any T1, CIS of the upper urinary tract is allowable if treated with complete nephroureterectomy more than 24 months prior to study enrollment. • Excluded: Participant has tumor(s) involving the prostatic urethra (ductal or stromal) on the screening biopsy. • Excluded: N+ and/or M+ per CT/MR urography.
5. 3. History of prior T2/T3 urothelial carcinoma of the bladder.
6. 4. Concurrent treatment with any chemotherapeutic agent.
7. 5. History of partial cystectomy for urothelial carcinoma.
8. 6. Treatment with last therapeutic agent (including BCG or intravesical chemotherapy post-TURBT) within 30 days of Screening for Phase 1, and for Phase 2, within at least 30 days of Screening and prior to the Screening biopsy, with the exception of cytotoxic agents (e.g., Mitomycin C, gemcitabine) when administered as a single instillation immediately following a TURBT procedure which is permitted 14 days or more prior to beginning study treatment.
9. 7. Patients who have received systemic immunosuppressive medication including high-dose corticosteroids (e.g., systemic corticosteroids 20 oral mg prednisone or equivalent) within 4 weeks prior to Day 1. Exception: intermittent or sporadic use of inhaled, topical or intra-articular steroids is allowed when given 14 days or more prior to enrollment. Notes: • Patients must not be receiving doses of 20 mg/day of oral prednisone or equivalent at the time of study entry or during the study. • Intravesical therapy within 8 weeks prior to beginning study treatment, with the exception of cytotoxic agents (e.g., Mitomycin C, gemcitabine, doxorubicin, and epirubicin) when administered as a single instillation immediately following a TURBT procedure, which is permitted 14 days or more prior to beginning study treatment. • Patients with contrast dye allergies may be given a single dose of a systemic steroid in order to complete a contrast-enhanced computerized tomography (CT) urogram (CT urogram) for trial purposes. A 14-day minimum separation of the steroid dose and detalimogene dose must occur.
10. 8. History of severe asthma or other respiratory diseases (bronchiectasis, tuberculosis, interstitial pneumonia, occupational lung disease, sarcoidosis, etc.); patients with objective evidence of radiation pneumonitis, drug-associated pneumonitis, or severe impairment of pulmonary function (e.g., requiring supplemental oxygen, chronic oral or inhaled steroids, or hospitalization within the past 6 months [prior to Day 1] for treatment of dyspnea or associated symptoms).
11. 9. History of lung lobectomy resulting in severe impairment of pulmonary function (e.g., requiring supplemental oxygen, chronic oral or inhaled steroids, or hospitalization within the past 6 months [prior to Day 1] for treatment of dyspnea or associated symptoms).
12. 10. History of unresolved vesicoureteral reflux or current indwelling indwelling urinary stent. (Note: any indwelling urinary stent[s] must be removed prior to detalimogene instillation).
13. 20. Known active human immunodeficiency virus, Hepatitis B (HBV), or Hepatitis C (HCV) infection. Exception for active HIV: patients who are currently stable on antiretroviral therapy (ART) for at least 4 weeks and agree to adhere to ART during study therapy, have HIV viral load of < 400 copies per milliliter (/mL) at screening (or undetectable per local criteria), and have CD4 T cell counts ≥ 200/microliter will be eligible for enrollment. Exception for active Hepatitis: For patients with evidence of HBV infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. For patients with HCV, infection must have been treated and cured or patients are currently on treatment and have an undetectable HCV viral load NOTE: HBV and HBC antibody or antigen positivity alone, in the absence of an active infection, does not exclude a patient.
14. 21. Significant cardiovascular risk (e.g., coronary stenting within 8 weeks, myocardial infarction within 6 months).
15. 22. Hypersensitivity to any of the excipients of the study drug.
16. 23. Consideration by the Investigator that the patient is an unsuitable candidate for the study; due to a personal issue (e.g., inability to comply with protocol or relationship to study staff or Sponsor), mental health considerations, or other reason, that may impede successful study participation. In the event of any unstable or clinically significant concurrent medical condition that would, in the opinion of the Medical Monitor, jeopardize the safety of a subject and/or their ability to comply with the protocol, enrollment will not be authorized by the Sponsor Medical Monitor.
17. 11. History of unresolved hydronephrosis due to ureteral obstruction.
18. 12. Participation in any other research protocol involving administration of an investigational agent (not approved) within 30 days prior to Screening, OR any prior treatment of NMIBC with any investigational gene or investigational immunotherapy agent.
19. 13. History of external beam radiation to the pelvis or prostate brachytherapy within the last 2 months of Screening.
20. 14. History of interstitial lung disease and/or pneumonitis in patients who have previously received a PD-1 or PD-L1 inhibitor therapy.
21. 15. Evidence of metastatic disease.
22. 16. History of difficult catheterization that in the opinion of the Investigator will prevent administration of EG-70.
23. 17. Current indwelling urinary catheter (including Foley catheters or suprapubic tubes); however, intermittent catheterization is acceptable.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percentage of patients with cystoscopic CR at any time, based on cystoscopic exam, urine cytology, and biopsies. Investigator assessment of response will be reviewed by central pathology laboratory adjudication (for NMIBC cohorts with CIS) when corresponding specimen is available for review.

Secondary endpoints 8

1. Progression-free survival
2. Recurrence-free survival for the NMIBC papillary-only cohort (Cohort 3).
3. Duration of response of the responding patients and percentage of patients with duration of response ≥ 1 year.
4. Cystectomy-free survival.
5. CR rate at landmark timepoints.
6. Health-related Quality of Life (EORTC Quality of Life Questionnaire Core 30 [QLQ-C30] and NMIBC-24)
7. Other endpoints: Anti-drug antibodies, EG-70 plasmid DNA in urine and blood, levels of IL-12 gene expression and RIG-I activators and/or biomarkers in specimens
8. Nature, incidence, relatedness, and severity of treatment-emergent AEs (as assessed by CTCAE v5.0).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Engene Inc.

Sponsor organisation

Engene Inc.

Address

4868 Levy Street Suite 220

City

Saint-Laurent

Postcode

H4R 2P1

Country

Canada

Scientific contact point

Organisation

Engene Inc.

Contact name

CMO

Public contact point

Organisation

Engene Inc.

Contact name

Medical Monitor

Third parties 7

Locations

4 EU/EEA countries · 35 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 60 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications