A 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 (HR-NMIBC)
- Conditions
- 'non-muscle invasive bladder cancer' and 'urothelial carcinoma'10004994
- Registration Number
- NL-OMON56283
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 14
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. 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-nai*ve. 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-grade Ta, 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. BCG-nai*ve (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. 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. 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. 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. Type of Participant 7. Eastern Cooperative Oncology
Group (ECOG) performance status Grade 0, 1, or 2. 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. 9.1 Criterion modified per Global
Amendment 1 9.2 Criterion modified per Global Amendment 2 Adequate bone marrow,
liver, and renal function: A. Bone marrow function (without the support of
cytokines or erythropoiesis stimulating agent in the preceding 2 weeks): i.
Absolute neutrophil count (ANC) >=1,000/mm3 ii. Platelet count >=75,000/mm3 iii.
Hemoglobin >=8.0 g/dL B. Liver function: i. Total bilirubin <=1.5 x ULN or direct
bilirubin < ULN for participants with total bilirubin levels >1.5xULN (except
participants with Gilbert*s Syndrome, who must have a total bilirubin <3.0
mg/dL), ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
<=2.5x institutional ULN C. Renal function: i. Creatinine clearance >30 mL/min
using the Cockcroft-Gault formula. (See Section 10.15: Appendix 15). Sex and
Contraceptive/Barrier Requirements For inclusion criteria 10-11 Please see the
protocol. Informed Consent 12. Criterion modified per Global Amendment 1 12.1
Participants must sign an informed consent form (ICF) (or their legally
acceptable representative must sign) indicating that he or she understands the
purpose of, and procedures required for, the study and is willing to
participate in the study
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. 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. 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. 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. 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. A history of
clinically significant polyuria with recorded 24-hour urine volumes greater
than 4000 mL. 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. 8.1. 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. 9. Indwelling catheters are not permitted; however, intermittent
catheterization is acceptable. 10. Participants must not have
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method