A Phase 3, Randomized, Study of Neoadjuvant Chemotherapy alone versus Neoadjuvant Chemotherapy plus Nivolumab or Nivolumab and BMS-986205, Followed by Continued Post- Surgery Therapy with Nivolumab or Nivolumab and BMS-986205 in Participants with Muscle- Invasive Bladder Cancer
- Conditions
- Muscle invastive bladder cancer10038364
- Registration Number
- NL-OMON52608
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 24
- Participants with MIBC, clinical stage T2-T4a, N0 (<10 mm on CT or MRI), M0,
diagnosed at
TURBT and confirmed by radiographic imaging. Variant histology is acceptable
if there is a
predominant urothelial component
- Participant must be deemed eligible for RC by his/her urologist and/or
oncologist, and must agree
to undergo RC after completion of neo-adjuvant therapy
- Prior BCG or other intravesical treatment of non-muscle invasive bladder
cancer (NMIBC) is
permitted if completed at least 6 weeks prior to initiating study treatment
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
- Life expectancy >= 6 months
- Documentation of PD-L1 status by immunohistochemistry (IHC) performed by the
central lab
during the screening period from the TURBT or biopsy that made the diagnosis
of MIBC. No
systemic therapy (eg, adjuvant or neoadjuvant chemotherapy) should be given
after the sample
was obtained. PD-L1 results are not required prior to beginning treatment on
the safety lead-in.
- Clinical evidence of positive LN (>= 10 mm in short axis) or metastatic
bladder cancer
- Prior systemic therapy, radiation therapy, or surgery for bladder cancer
other than TURBT or
biopsies is also not permitted
- Ineligible to receive cisplatin due to Grade 2 or higher peripheral
neuropathy or audiometric
hearing loss, or calculated (Cockcroft-Gault formula) GFR or measured
(24-hour urine) creatinine
clearance (CrCl) < 50 mL/min
- Participants with an active, known or suspected autoimmune disease.
Exceptions per protocol
- Participants with conditions known to interfere significantly with the
absorption of oral medication,
as per investigator judgement
- Participants with a condition requiring systemic treatment with either
corticosteroids (> 10 mg daily
prednisone equivalent) or other immunosuppressive medications within 14 days
of randomization.
Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg
daily prednisone
equivalent, are permitted in the absence of active autoimmune disease
- Participants with uncontrolled adrenal insufficiency
- Participants with a personal or family (i.e., in a first-degree relative)
history or presence of
cytochrome b5 reductase deficiency (previously called methemoglobin
reductase deficiency) or
other diseases that puts them at risk of methemoglobinemia. All participants
will be screened for
methemoglobin levels prior to randomization.
- Participants with a history of G6PD deficiency or other congenital or
autoimmune hemolytic
disorders. All participants will be screened for G6PD deficiency prior to
randomization.
- Major surgical procedure within 14 days prior to initiating study treatment
or anticipation of the
need for a major surgical procedure (other than RC) during the course of the
study.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p> - pCR rate, defined by the proportion of randomized participants with absence<br /><br>of any cancer (T0, N0, M0) in pathology specimens after RC, based on<br /><br>blinded pathology review.<br /><br><br /><br>- EFS, defined as the time from randomization to any of the following events:<br /><br>progression of disease that precludes RC surgery, local or distant<br /><br>recurrence, based on BIRC assessments, or death due to any cause.<br /><br><br /><br>- pCR rate, defined by the proportion of randomized participants with absence<br /><br>of any cancer (T0, N0,M0) in pathology specimens after RC, based on<br /><br>blinded pathology review.<br /><br><br /><br>- EFS, defined as the time from randomization to any of the following events:<br /><br>progression of disease that precludes RC surgery, local or distant<br /><br>recurrence based on BIRC assessments, or death due to any cause.</p><br>
- Secondary Outcome Measures
Name Time Method <p> - OS, defined as the time between the date of randomization and the date of<br /><br>death from any cause.<br /><br><br /><br>- Incidence of adverse events (AEs), serious AEs, deaths and laboratory<br /><br>abnormalities in participants who received at least one dose of study<br /><br>treatment.</p><br>