Abstract
e15727 Background: Overexpression of transforming growth factor-beta 2 (TGF-b2) is associated with poor prognosis and plays a key role for malignant progression of various tumors by inducing proliferation, metastasis, angiogenesis and immunosuppression. Methods: A total of 37 patients with advance pancreatic cancer were treated with Trabedersen (OT-101) by intravenous infusion in escalating doses of 2 treatment schedules (initial schedule: 7-days on, 7-days off; modified schedule: 4-days on, 10-days off; two cycles as core study and up to 10 cycles for expanded study). Results: MTD for 7/7 regimen (N = 11) was 160 mg/m2/d; whereas MTD was not reached on 4/10 regimen (N = 27) even at highest dose of 330 mg/m2/d. There was 16 2nd line patients and 11 3rd line and beyond on 4/10 regimen. The PFS/OS of these 2nd line patients in months were: 1.87/5.60 (N = 6), 1.87/9.93 (N = 11) and 2.72/11.80 (N = 5) at increasing mean dose of 140, 167, and 196, respectively. The OS of 9.93 and 11.80 are higher than the highest reported in the 65 trials reported in the literature during 1997-2015 (range = 2.50-9.20/median = 5.50). The corresponding PFS values were in line with reported literarure (range = 0.00-7.65/median = 2.43). The OS of this 4/10 cohort treated with subsequent chemotherapies was 14.7 and 2.93 mos with and without subsequent chemotherapies, p = 0.0023. Chemotherapy on 2ndline followed with subsequent Trabedersen 4/10 regimen as third line was ineffective with OS of 2.80 mos (N = 9) versus 9.93 mos (N = 11), p = 0.046. Conclusions: Trabedersen (OT-101) treatment was characterized by outstanding OS which was not supported by PFS. The effect was seen primarily when chemotherapies were used as third line after Trabedersen treatment; OS benefit was not observed for the converse- chemotherapies used first followed by Trabedersen. The data support the enhancement of subsequent chemotherapies following Trabedersen treatment suggesting a combination trial of Trabedersen and chemotherapies with sequencing. Clinical trial information: NCT00844064.
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