A Phase 3, Randomized, Open-label Study of NKTR-214 Combined with Nivolumab Versus Nivolumab in Participants with Previously Untreated Unresectable or Metastatic Melanoma
- Conditions
- Melanoma10040900
- Registration Number
- NL-OMON52577
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 35
a) Participants must have an Eastern Cooperative Oncology Group (ECOG)
performance status of <= 1 (adults 18 years or older) or/Lansky Performance
Score >= 80% (for minors (ages 12-17 only)
b) Histologically confirmed stage III (unresectable) or stage IV melanoma, as
per American Joint Committee on Cancer (AJCC) staging system, 8th edition
c) Treatment-naïve participants (ie, no prior systemic anticancer therapy for
unresectable or metastatic melanoma) with the exception of prior adjuvant
treatment for melanoma with approved agents (eg, BRAF/MEK inhibitors,
ipilimumab, nivolumab, pembrolizumab or interferon). Participants who have had
a recurrence within the 6 months of completing adjuvant treatment are not
eligible.
d) Measurable disease by computed tomography (CT) or magnetic resonance imaging
(MRI) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria
e) Either a formalin-fixed, paraffin-embedded (FFPE) tissue block or unstained
tumor tissue sections, obtained within 3 months prior to enrollment, with an
associated pathology report, must be submitted to the core laboratory for
inclusion. FFPE tissue block and unstained slides submitted should be from
biopsy obtained within 6 months prior to enrollment. Unstained slides should be
sectioned within 3 months prior to submission.
i) To be randomized, a participant must be classified as PD-L1 positive (>=
% tumor cell membrane staining) vs PD-L1 negative (< 1% tumor cell membrane
staining)/PD-L1 indeterminate (tumor cell membrane scoring hampered by high
cytoplasmic staining or melanin content). Not evaluable participants are not
eligible for randomization.
f) Participants must have known BRAF V600 mutation status or consent to BRAF
V600 mutation testing per local institutional standards by approved methodology
during the Screening period.
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) Uveal melanoma is excluded.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The efficacy endpoints of ORR, PFS and OS were assessed by a BICR.<br /><br>The addition of bempegaldesleukin to nivolumab did not result in a<br /><br>statistically significant improvement in PFS (HR 1.09, 97% CI, 0.88-1.35) or<br /><br>ORR compared to nivolumab monotherapy as assessed by Blinded Independent<br /><br>Central Review (BICR), and the significance threshold for OS<br /><br>was also not crossed at the combined first and second OS analyses.<br /><br>Furthermore, there was added toxicity with bempegaldesleukin plus nivolumab<br /><br>compared to nivolumab monotherapy including NK a higher incidence of<br /><br>drug-related adverse events (AEs), drug-related serious adverse events (SAEs)<br /><br>and drug-related AEs leading to study treatment discontinuation.</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.<br /><br><br /><br>Per Protocol Amendment 03, the secondary and exploratory objectives except<br /><br>biomarker parameters are no longer applicable. Biomarker sample collection will<br /><br>not be applicable per Protocol Amendment 03. However, exploratory analysis of<br /><br>biomarkers on previously collected specimens may be conducted.</p><br>