Melanoma
Conditions
Interventions
Subjects received open-label treatment with nivolumab (flat dose 360 mg every 3
weeks) in combination with NKTR-214 (0.006 mg/kg every 3 weeks) or Nivolumab
monotherpy (flat dose 360 mg every 3 week
Sponsors
Bristol-Myers Squibb
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: a) Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of = 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 (
Exclusion criteria
Exclusion criteria: 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The efficacy endpoints of ORR, PFS and OS were assessed by a BICR. The addition of bempegaldesleukin to nivolumab did not result in a statistically significant improvement in PFS (HR 1.09, 97% CI, 0.88-1.35) or ORR compared to nivolumab monotherapy as assessed by Blinded Independent Central Review (BICR), and the significance threshold for OS was also not crossed at the combined first and second OS analyses. Furthermore, there was added toxicity with bempegaldesleukin plus nivolumab compared to nivolumab monotherapy including NK a higher incidence of drug-related adverse events (AEs), drug-related serious adverse events (SAEs) and drug-related AEs leading to study treatment discontinuation. | — |
Secondary
| Measure | Time frame |
|---|---|
| Further efficacy endpoints will be assessed by BICR and the investigator and in correlation with biomarker analysis. Safety and tolerability will be assessed by review of Incidence of adverse events, serious adverse events, and select adverse events. Per Protocol Amendment 03, the secondary and exploratory objectives except biomarker parameters are no longer applicable. Biomarker sample collection will not be applicable per Protocol Amendment 03. However, exploratory analysis of biomarkers on previously collected specimens may be conducted. | — |
Countries
Netherlands
Outcome results
None listed