The ongoing nonrandomized, open-label, single-arm phase 2 NICE-NEC trial is evaluating the safety and efficacy of adding the immune checkpoint inhibitor nivolumab to standard platinum-doublet chemotherapy as first-line therapy in patients with metastatic or unresectable grade 3 neuroendocrine neoplasms (NENs) of gastroenteroenpathic (GEP) or unknown origin.
Grade 3 NENs are aggressive cancers, with median overall survival (OS) of approximately 12 months associated with standard-of-care platinum-based chemotherapy, underscoring the need for novel treatment approaches. Programmed cell death-ligand 1 expression is elevated in grade 3 NENs, suggesting potential sensitivity to immune checkpoint inhibitors. Subgroup analysis of the CA209-538 study showed an overall response rate of 43% in patients with pancreatic NENs treated with nivolumab and ipilimumab, indicating potential antitumor activity.1 To assess the clinical benefit of immune therapy, the nonrandomized, open-label, single-arm phase 2 NICE-NEC trial is recruiting patients with metastatic or unresectable grade 3 NENs of GEP or unknown origin across 12 Spanish centers from the Spanish Taskforce of Neuroendocrine Tumors to assess the safety and efficacy of adding immune checkpoint inhibitors to standard chemotherapy as first-line therapy. Study details were presented at the European Society for Medical Oncology Virtual Congress 2020.
Eligibility criteria include histologically confirmed grade 3 NENs in the GEP tract, as well as grade 3 NENs of unknown primary; metastatic or locally advanced unresectable disease; no prior systemic treatment for advanced disease or adjuvant therapy; Ki67 >20% or mitotic rate >20 per 10 high-power field; and Eastern Cooperative Oncology Group performance status 0 to 2. The overall study design is comprised of an initial induction phase, followed by maintenance treatment and a follow-up phase. Treatment in the induction phase consists of 6 cycles of nivolumab 360 mg every 3 weeks in combination with carboplatin area under the curve 5 on day 1, plus etoposide 100 mg/m2 on days 1 to 3 every 3 weeks administered intravenously; maintenance treatment is nivolumab 480 mg administered intravenously every 4 weeks, for up to 2 years or until disease progression.
The primary end point is 1-year OS rate; secondary end points include objective response rate, progression-free survival, duration of response according to Response Evaluation Criteria in Solid Tumors version 1.1, and safety (incidence of adverse events [AEs], serious AEs, and selected AEs). Serial blood samples (serum and plasma at baseline and at disease progression or end of treatment) will be collected for biomarker analysis to identify prognostic and/or predictive factors of response to nivolumab and carboplatin-etoposide chemotherapy, including chromogranin A and enolase. Mutational burden, gene-expression signature, soluble factors, and other molecular markers in peripheral blood will also be tested to characterize the genetic and molecular landscape of the tumors.
To test the primary objective, the sample size was estimated to be 38 patients, calculated with 80% power and yielding a 2-sided type I error rate of 5% when the true 1-year OS rate is 0.72. Accrual for the NICE-NEC trial was initiated in October 2019. The trial is currently recruiting patients, with 16 patients enrolled to date; the last patient of the last visit is expected for the second quarter of 2022.
Source: Riesco Martínez MC, et al. Ann Oncol. 2020;31(suppl 4). Abstract 1188TiP.
1. Klein O, Kee D, Markman B, et al. Immunotherapy of ipilimumab and nivolumab in patients with advanced neuroendocrine tumors: a subgroup analysis of the CA209-538 clinical trial for rare cancers. Clin Cancer Res. 2020;26:4454-4459.