Checkpoint inhibition as monotherapy has limited success in advanced metastatic epithelial ovarian cancer (epOC) and strategies to increase immunogenicity are needed. 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 expression of MHC, which enables tumor antigen presentation in neoplasias of low mutational burden (eg, epOC) and promotes immunosurveillance by expanding effector memory T cells (Mumm et al 2010, 2011). Pegilodecakin reduces tumor inflammatory processes such as angiogenesis and metastatic dissemination (Oft 2017), the off-target auto-immune side effects of immunotherapy and the inflammatory-related side effects of some chemotherapies. Preclinical data suggest synergy of pegilodecakin in reducing tumor volume when combined with platinum/taxane based chemotherapy.
In a 353 pt phase 1/1b dose escalation and expansion study conducted in the US (2013-2017), 12 platinum-refractory, heavily pretreated epOC pts received daily pegilodecakin alone (N = 9) or in combination with platinum/taxane-based chemotherapy (N = 3). Responses were assessed by irRC.
In monotherapy 4 (44%) had a PFS of more than 3.5 months and a survival of more than 14.7 months. No IRAEs were seen. G3/4 TrAEs in monotherapy: anemia (33%), fatigue (33%), thrombocytopenia (22%); in platinum/taxane combo: anemia (33%), diarrhea (33%), neutropenia (33%), thrombocytopenia (33%).Table: 1146P
|Regimen||E (ITT)3||Median (Range)||%||%||mos||mos|
|Monotherapy1||9 (9)||5 (4-11)||-||66.7||2.4||13.8|
|Plus Chemotherapy2||3 (3)||2 (1-7)||-||66.7||5.2||10.7|
1.0 or 20 µg/kg;2
Pegilodecakin 10 µg/kg + Carboplatin + Paclitaxel or Pegilodecakin 10 µg/kg + Cisplatin + Paclitaxel or Pegilodecakin 2.5 µg/kg + Carboplatin + Docetaxel;3
E (evaluable - baseline tumor assessment + >1 post-baseline assessments, and no major protocol deviations); ITT (intent to treat); Data cut on 05.01.18.
Pegilodecakin alone demonstrated durable disease control with manageable toxicity in a proportion of treatment refractory epOC pts. Preliminary findings in a small subset of epOC pts who received pegilodecakin in combination with platinum plus taxane-based chemotherapy yielded promising results.
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.