Phase 3, Open-Label, Multi-Center, Randomized Study Evaluating the Efficacy and Safety of TAR-200 in Combination with Cetrelimab or TAR-200 Alone Versus Intravesical Bacillus Calmette-Guérin (BCG) in Participants with BCG-naïve High-Risk Non-Muscle Invasive Bladder Cancer (HRNMIBC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Janssen - Cilag International

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

23 Mar 2023 → ongoing

Decision date (initial)

2024-04-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-507187-39-00

EudraCT number

2020-004506-64

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Pharmacodynamic, Therapy, Safety

To compare event-free survival (EFS) in participants with BCG-naïve HRNMIBC (high-grade papillary Ta, any T1, or CIS), receiving TAR-200 + IV cetrelimab (Group A) versus intravesical BCG (Group B) and TAR-200 alone (Group C) versus intravesical BCG (Group B).

Conditions and MedDRA coding

High-Risk Non-muscle-invasive Bladder Cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparecy. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age 1. Age ≥18 years (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent.
2. Disease Characteristic 2. Criterion modified per Global Amendment 1 2.1 Criterion modified per Global Amendment 2 2.2 Histologically confirmed initial diagnosis by local pathology (within 90 days of the most recent signed informed consent) of HR-NMIBC (high-grade Ta,any T1 or CIS), [AJCC 2017], in participants who are BCG-naïve. Mixed histology tumors are allowed if urothelial differentiation (transitional cell histology) is predominant. However, the presence of neuroendocrine, micropapillary, signet ring cell, plasmacytoid, or sarcomatoid features will make a participant ineligible. Participants may have had a history of HR-NMIBC (defined as high-gradeTa, any T1, or CIS) as long as it has been >3 years from current/novel diagnosis of HR-NMIBC (high-grade Ta, any T1 or CIS).
3. 3. BCG-naïve (participants who have not received prior intravesical BCG or who previously received but stopped BCG more than 3 years before date of randomization are eligible) (Kamat 2016).
4. 4. Participants must be willing to undergo all study procedures (eg, multiple cystoscopies from Screening through the end of study and TURBT/bladder biopsy for assessment of recurrence/progression).
5. 5. Criterion modified per Global Amendment 2 5.1 All visible papillary disease must be fully resected (absent) prior to date of randomization and documented at baseline cystoscopy. Local urine cytology at screening must be negative or atypical (for HGUC) for patients with papillary only disease (without CIS).
6. 6. All AEs associated with any prior surgery and/or intravesical therapy must have resolved to CTCAE version 5.0 Grade <2 prior to date of randomization.
7. Type of Participant 7. Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2.
8. 8. Thyroid function tests within normal range or stable per Investigator assessment. Investigators may consult an endocrinologist for participant eligibility assessment in the case of equivocal or marginal tests results.

Exclusion criteria 8

1. Disease Characteristics 1.Criterion modified per Global Amendment 1 1.1 Presence or history of histologically confirmed, muscle invasive, locally advanced, nonresectable, or metastatic urothelial carcinoma (ie, ≥T2).
2. 2. Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder (ie, urethra, ureter, or renal pelvis). Ta/any T1/CIS of the upper urinary tract (including renal pelvis and ureter) is allowable if treated with complete nephroureterectomy more than 24 months prior to randomization.
3. 3. Criterion modified per Global Amendment 2 3.1 N+ and/or M+ per blinded independent central review (BICR) of computed tomography/magnetic resonance (CT/MR) Urography and chest CT. Any history of HR-NMIBC (high-grade Ta, any T1 or CIS) <3 years from current diagnosis.
4. Medical Conditions 4.1 Active malignancies (ie, progressing or requiring treatment change in the last 24 months prior to randomization) other than the disease being treated under study. Potential allowed exceptions include the following (others may be allowed with Sponsor approval). a. skin cancer (non-melanoma or melanoma) that is considered completely cured. b. non-invasive cervical cancer treated that is considered completely cured. c. adequately treated lobular carcinoma in situ (LCIS) and ductal CIS d. history of localized breast cancer and receiving antihormonal agents e. history of localized prostate cancer (N0M0) and receiving androgen deprivation therapy f. Locerion modified per Global Amendment 2alized prostate cancer (N0M0): i. with a Gleason score of 6, treated within the last 24 months or untreated and under surveillance, ii. 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, iii. or history of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence.
5. 5. Presence of any bladder or urethral anatomic feature (eg, urethral stricture) that, in the opinion of the Investigator, may prevent the safe insertion, indwelling use, removal of TAR-200, or administration of intravesical BCG. Participants with tumors involving the prostatic urethra in men will be excluded.
6. 6. A history of clinically significant polyuria with recorded 24-hour urine volumes greater than 4000 mL.
7. 7.1 Received a live virus vaccine within 30 days prior to the initiation of study treatment. Inactivated (non-live, or non-replicating) vaccines approved or authorized for emergency use (eg,COVID-19) by local health authorities are allowed.
8. 8.1. Participants should not have a history of acute ischemic heart disease within 42 days of randomization, or history of uncontrolled cardiovascular disease including any of the following in the 3 months prior to randomization: a. unstable angina, b. myocardial infarction, c. ventricular fibrillation, d. Torsades de Pointes, e. cardiac arrest, or known congestive New York Heart Association Class III-IV heart failure, f. cerebrovascular accident, g. transient ischemic attack, or h. pulmonary embolism or other venous thromboembolism in the 3 months prior to randomization.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. EFS will be measured as the time from randomization to either the time of the first recurrence of high-risk disease, progression, or death due to any cause, whichever occurs first. For participants with CIS, persistent disease at 6 months (Week 24) is also considered an EFS event. Progression is defined as: 1) an increase of stage from Ta to T1 or from CIS to T1, or 2) progression to MIBC (T≥2) or to lymph node (N+) or to distant disease (M+), whichever occurs first.

Investigational products

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

Test 3

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Janssen - Cilag International

Sponsor organisation

Janssen - Cilag International

Address

Turnhoutseweg 30

City

Beerse

Postcode

2340

Country

Belgium

Scientific contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Public contact point

Organisation

Janssen - Cilag International

Contact name

CTIS Point of Contact

Third parties 12

Locations

9 EU/EEA countries · 69 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 110 files

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

Application history

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