A Randomized, Open-Label, Phase 2 Study of Nivolumab in Combination with Ipilimumab or Nivolumab Monotherapy in Participants with Advanced or Metastatic Solid Tumors of High Tumor Mutational Burden (TMB-H)
- Conditions
- Solid TumorsMetastatic10027476
- Registration Number
- NL-OMON52919
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 13
a) Participants with a refractory, metastatic, or unresectable
histologically or cytologically
confirmed solid malignant tumor with TMB-H who are refractory to standard local
therapies, or for which no standard treatment is available., b)Either a
formalin-fixed, paraffin-embedded (FFPE) tissue block or unstained tumor tissue
sections, obtained within 9 months and no additional intervening therapy
(excluding
palliative therapy) prior to enrollment, with an associated pathology report,
must be
submitted to the core laboratory for inclusion. Biopsy should be excisional,
incisional or
core needle. Fine needle aspiration is unacceptable for submission., c) The IRT
must be provided with the results of both tissue and blood TMB-H testing for
eligible participants prior to randomization. Both results are utilized for
stratification purposes.
d) Prior TMB-H results obtained with F1CDx assay (tissue) or assay from
Foundation Medicine (blood) are acceptable for eligibility purposes. When these
prior results are not available, tissue and / or blood samples must be provided
for central TMB-H testing, and results must be available prior to
randomization.
i) Participants must have either tTMB or bTMB >= 10 mut/Mb (tTMB >= 10 mut/Mb or
the
new cutoff value of bTMB determined by the 1st interim analysis). Should one of
the
two populations (tTMB-H or bTMB-H) reach the targeted sample size before the
other,
then enrollment will continue only with participants for the other TMB-H
population.
ii) TMB results obtained from any other methodologies are not acceptable for
eligibility.
d) Participants must have measurable disease for response assessment as per
RECIST 1.1 for solid tumors other than CNS, and RANO criteria for primary CNS
malignancies.
a) Active brain metastases or leptomeningeal metastases. Participants with
brain metastases are eligible if these have been treated and there is no MRI
evidence of progression for at least 8 weeks after treatment is complete and
within 28 days prior to first dose of study treatment administration.
b) There must also be no requirement for immunosuppressive doses of systemic
corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior
to study treatment administration. Stable dose of anticonvulsants is allowed.
c) Patient who received whole brain radiation therapy are not eligible.
d) Participants who received prior treatment with an anti-PD-1, anti-PD-L1,
anti-PD-L2, anti CD137, or anti-CTLA-4 antibody, or any other antibody or drug
specifically targeting T-cell co-stimulation or checkpoint pathways
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>BICR-assessed ORR using RECIST 1.1, and Response Assessment for Neuro-Oncology<br /><br>(RANO) criteria in primary CNS tumors </p><br>
- Secondary Outcome Measures
Name Time Method <p>Further efficacy endpoints will be assessed by BICR and the investigator and in<br /><br>correlation with biomarker analysis.<br /><br>Safety and tolerability will be assessed by review of Incidence of adverse<br /><br>events, serious adverse events, and select adverse events</p><br>