Pegilodecakin as monotherapy or in combination with anti‐PD ‐1 or tyrosine kinase inhibitor in heavily pretreated patients with advanced renal cell carcinoma: Final results of cohorts A, G, H and I of IVY Phase I study
Autor: | Kyriakos P. Papadopoulos, David Ferry, Manuel Afable, Nizar M. Tannir, Alexandra Drakaki, Annie Hung, Jong Seok Kim, Johanna C. Bendell, Raid Aljumaily, Deborah J. Wong, Aung Naing |
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Rok vydání: | 2021 |
Předmět: |
Cancer Research
medicine.medical_specialty medicine.drug_class business.industry Pembrolizumab medicine.disease Gastroenterology Tyrosine-kinase inhibitor Pazopanib 03 medical and health sciences 0302 clinical medicine Oncology Tolerability Renal cell carcinoma 030220 oncology & carcinogenesis Internal medicine Toxicity medicine Nivolumab business CD8 medicine.drug |
Zdroj: | International Journal of Cancer. 149:403-408 |
ISSN: | 1097-0215 0020-7136 |
Popis: | Interleukin (IL)-10 has anti-inflammatory and CD8+ T-cell-stimulating properties. Pegilodecakin (pegylated recombinant human IL-10) induces intratumoral antigen-specific CD8 + T-cells and upregulates IFNγ and major histocompatibility complexes (MHC) I and II. Pegilodecakin has single-agent activity with manageable toxicity in advanced renal cell carcinama (aRCC) (data cutoff 24 March 2016). Pegilodecakin with pembrolizumab or nivolumab revealed clinical activity in aRCC (data cutoff 1 July 2018). Here, we report for the first time the results of pegilodecakin+ pazopanib, and final results for monotherapy and long-term follow-up with pegilodecakin + anti-programmed cell death 1 (anti-PD-1) inhibitors (data cutoff 19 February 2019). Phase 1/1b multi-cohort dose escalation IVY study enrolled 353 patients. Sixty-six patients with aRCC were treated with pegilodecakin alone or with pazopanib or anti-PD-1 inhibitor in cohorts A, G, H and I (data cutoff 19 February 2019). Primary endpoints included safety and tolerability. Secondary endpoint was tumor response by immune-related response criteria (irRC). Pegilodecakin plus nivolumab or pembrolizumab yielded median progression-free survival (mPFS) of 13.9 months and 6-month PFS probability of 60%, 76% 1-year overall survival (OS) probability and 61% 2-year OS probability. Pegilodecakin monotherapy produced mPFS of 1.8 months, 6-month PFS probability 25%, 1-year OS 50%, and 2-year OS 17%. Median OS was not reached in both combinations. Objective response rates (ORRs) were 33% with pazopanib and 43% with anti-PD-1. Most common Grade 3/4 treatment-related adverse events included anemia, thrombocytopenia and hypertriglyceridemia. In these heavily pretreated renal cell carcinama cohorts of IVY, pegilodecakin+anti-PD-1 inhibitor showed promising clinical activity. Safety profile of pegilodecakin alone and with anti-PD-1 inhibitors was consistent as previously reported. |
Databáze: | OpenAIRE |
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