Abstract
54 Background: Escalating Intratumoral heterogeneity resulting in xenogenization which is countered by overexpression of TGF-β. Here we report on the use of OT-101/Chemo to break immune tolerance to cure pancreatic cancer (PC). OT-101 is an antisense against TGF-β2. Methods: Total of 37 pts 2nd line and beyond received OT-101 with option to go on subsequent Chemo (OT-101/Chemo) or Best Supportive Care (BSC) (OT-101/BSC). Stratification by treatment line, schedule, metastasis location, disease control (DC), and baseline CA19-9, was performed. Plasma levels of 31 cyto-/chemokine were measured in a subset of 12 pts. Results: mOS of the 18 pts receiving OT-101/Chemo was 9.4 mos vs. OT-101/BSC (2.8 mos, p=0.0004). No significance was observed on stratification. However, pts with only liver metastasis had a mOS of 9.5 mos while those with liver metastasis and others only had a mOS of 4.7 mos (p=0.0077). Among the former, 1006 has Complete Response beyond 77.3 mos and 1022 had Stable Disease with OS of 40.3 mos; and OS was higher with OT-101/Chemo – 12.4 mos versus 1.9 mos, p=0.0006. There were 16 of 37 pts with DC, with mOS of 9.7 mos vs. 3.0 mos (p<0.0001); and OS was higher with OT-101/Chemo – 11.8 mos vs. 5.0 mos, p=0.0021. Pts exhibited spike in IL-8 level which returned to basal level at treatment stop. R squares relating the IL-8 spike and OS were 0.8522 and 0.9895 and p values were 0.0011 and 0.0053 for OT-101/Chemo and OT-101/BSC, respectively. Preclinically, OT-101 enhanced PBMC activity in cell kill assay and in vivo xenograft. Conclusions: The MOA for OT-101/Chemotherapy is consistent with the reactivation of immunity during TGF-β suppression and subsequent boosting/expansion of immunity during Chemo. Contrary to traditional tumor vaccine- this is universally applicable to all patients.
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