Pegilodecakin (AM0010) is a pegylated recombinant human interleukin-10 that stimulates activation, survival and clonal expansion of intra-tumoral, tumor antigen specific CD8+ T cells. Pegilodecakin also up-regulates IFNγ and the expression of MHC, which enables tumor antigen presentation in neoplasias of low mutational burden and promotes immunosurveillance by expanding effector memory T cells (Mumm et al. 2010, 2011). Finally, pegilodecakin reduces tumor inflammatory processes such as angiogenesis and and metastatic dissemination (Oft 2017), the off-target auto-immune side effects of immunotherapy and the inflammatory-related side effects of some chemotherapies.
In a 353 patient phase 1/1b dose escalation and expansion study conducted in the US from 2013 to 2017, 37 pretreated RCC subjects received pegilodecakin with pembrolizumab or nivolumab. Responses were assessed by irRC.
TrAE were reversible and transient. G 3/4 TrAE in pts who received pegilodecakin (20 ug/kg) + nivo or pembro included anemia (10), thrombocytopenia (7) and hypertriglyceridemia (6). Pts on 10 ug/kg pegilodecakin + nivo or pembro did not have G3/4 anemia or thrombocytopenia.Table: 1130O
|Regimen||E (ITT)5||Median (Range)||%||%||mos||mos||OS (%)||All Grades (%)||Grades 3 & 4 (%)|
|Monotherapy1||16 (19)||3 (0-7)||25.0||56.0||1.9||9.8||-||5.3||0.0|
|Plus Pembrolizumab2||8 (8)||2 (0-5)||50.0||100||16.7||NR||88.0||-||-|
|Plus Nivolumab3||26 (29)||1 (0-5)||39.0||81.0||10.1||NR||89.0||-||-|
|Pooled Plus Anti-PD-14||34 (37)||2 (0-5)||41.0||85.0||12.5||NR||89.0||16.2||5.4|
20µg/kg QD, SC;2
2mg/kg, q3wk IV;3
3mg/kg, q2wk IV;4
pembrolizumab and nivolumab cohorts combined;5
E (evaluable - baseline tumor assessment + >1 post-baseline assessments, and no major protocol deviations); ITT (intent to treat);6
irAE - Immune-Related Adverse Events (e.g. pneumonitis, adrenal insufficiency, thyroiditis, hypothyroiditis, hypophysitis, mucositis/stomatis, colitis, hepatitis, cholangitis, polyarthritis, myasthenia gravis, optic neuritis); Data cut on 05.01.18; Median follow-up for pembrolizumab cohort 34.6 months (12.3-36.2 months); Median follow-up for nivolumab cohort 18.9 months (0.5-25.9 months)
Pegilodecakin when combined with anti-PD-1 therapy in advanced RCC patients was associated with response rates and durability of benefit greater than has been seen with anti-PD-1 alone. These preliminary findings support further studies of pegilodecakin with anti-PD-1 therapies.
Clinical trial identification
Legal entity responsible for the study
A. Hung, M. Oft, J. Leveque: Employee: ARMO BioSciences. All other authors have declared no conflicts of interest.