Abstract 5015
Background
Late line, triple negative breast cancer (TNBC) is an unmet need. 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.
Methods
In a 353 patient phase 1/1b dose escalation and expansion study conducted in the US from 2013 to 2017, 18 heavily pretreated TNBC subjects received pegilodecakin alone (N = 8) or in combination with platinum and taxane-based chemotherapy (N = 8) or platinum and gemcitabine chemotherapy (N = 10). Responses were assessed by irRC.
Results
G3/4 TrAEs in monotherapy are anemia (38%), thrombocytopenia (38%) and fatigue (25%); and in the platinum/taxane combo: anemia (75%), neutropenia (75%), thrombocytopenia (75%), leukopenia (50%), and febrile neutropenia (25%); in carbo/gem combo: thrombocytopenia (60%), fatigue (30%) and anemia (20%).Table: 1145P
| Pegilodecakin | N | Prior Therapies | ORR | DCR | mPFS | mOS |
|---|---|---|---|---|---|---|
| Regimen | E (ITT)5 | Median (Range) | % | % | mos | mos |
| Monotherapy1 | 4 (8) | 5 (3-8) | - | 25.0 | 2.0 | 5.3 |
| Plus Chemotherapy 12 | 7 (8) | 4 (2-5) | 28.6 | 71.4 | 3.9 | 11.2 |
| Plus Chemotherapy 23 | 9 (10) | 3 (1-5) | - | 55.6 | 3.3 | 6.8 |
| Pooled Plus Chemotherapy4 | 16 (18) | 4 (1-5) | 12.5 | 62.5 | 3.7 | 8.0 |
20µg/kg QD SC;
2Pegilodecakin 10 µg/kg + Carboplatin + Paclitaxel or Pegilodecakin 2.5 or 10 µg/kg + Carboplatin + Docetaxel or Pegilodecakin 10 µg/kg + Cisplatin + Paclitaxel or Cisplatin + Docetaxel;
3Pegilodecakin 5.0 or 10 µg/kg + Carboplatin + Gemcitabine;
4Chemotherapy cohorts 1 & 2 combined;
5E (evaluable - baseline tumor assessment + >1 post-baseline assessments, and no major protocol deviations); ITT (intent to treat); Data cut on 05.01.18.
Conclusions
Pegilodecakin in combination with platinum and taxane-based chemotherapy in advanced TNBC was associated with objective responses and durable clinical benefit as measured by disease control and overall survival. These preliminary findings support further studies of pegilodecakin in combination with standard of care chemotherapy in both later and earlier stages patients with TNBC.
Clinical trial identification
NCT02009449.
Legal entity responsible for the study
ARMO BioSciences.
Funding
ARMO BioSciences.
Editorial Acknowledgement
Disclosure
A. Hung, M. Oft, J. Leveque: Employee: ARMO BioSciences. All other authors have declared no conflicts of interest.