LBA19A MULTI-INSTITUTIONAL RANDOMIZED PHASE 2 TRIAL OF THE ONCOLYTIC VIRUS REOLYSIN IN THE FIRST LINE TREATMENT METASTATIC ADENOCARCINOMA OF THE PANCREAS (MAP)

ABSTRACT Aim: Reovirus is a naturally occurring virus that causes oncolysis in tumor cells with a Ras-activated pathway. It acts synergistically with taxanes. Since most pancreas cancer cells have downstream activated Ras we hypothesized that pts with MAP are susceptible to reovirus. Methods: We conducted an NCI-sponsored phase II study with a goal of 70 evaluable MAP pts randomized in a 1:1 allocation to paclitaxel [P (175 mg/m2)], carboplatin [C (AUC 5)] on day 1 with reovirus [R (3 x 1010 TCID50) iv] on days 1-5 {Arm A} vs P/C alone {Arm B} on day 1 of a 21-day cycle. The primary endpoint is progression-free survival (PFS). Secondary endpoints include safety, objective response rate (ORR), and overall survival (OS). Pts progressing on B were allowed to crossover to A. Eligible pts had no prior chemotherapy. Pre-treatment tissue was required for KRAS mutation status from DNA analysis. Analyses of immunomodulatory effects of therapy were performed. Results: Refer to Table 1 for key characteristics. Most common grade 3-4 toxicities include neutropenia (53%) and leucopenia (36%) with no overall difference between arms. In evaluable pts, ORR/SD was 22%/59% (A) and 21%/47% (B). To date, 81% have progressed, and median follow-up of 3.75 mo in event-free pts. PFS was similar in both arms (A: median 4.63 vs B: 5.1 mos; HR = 1.07, p = 0.81). The results held after sensitivity analyses and adjusting for factors such as KRAS. In 60 patients with KRAS analysis, a trend toward improved overall PFS in KRAS WT (6.0 mo) vs MT (4.3 mo); p = 0.20. In the KRAS MT group, an early limited differential in PFS between arm A (4.63 mo) vs B (4.34 mo); p = 0.73. 16 pts crossed over from B to A with 1 PR, 6 SD, 7 PD and 2 NA. Characteristic Arm A Arm B p-value Total N = 73 36 37 Age (Median, yrs) 61.5 66 0.055 ECOG PS (0/1), N 20/16 17/20 0.49 Baseline Ca 19-9 of > 59x ULN, % 53% 75% 0.14 KRAS Status ( MT), % 70% 77% 0.99 Pancreas Tumor Location, % Head Body Tail NS 22 36 22 22 27 38 19 14 Number of Metastatic Sites, % 1 2 >2 19 30 51 22 14 66 0.51 Conclusions: Reovirus can be administered safely in combination with P/C in pts with MAP. Both arms performed better than historical control, but R did not seem to improve outcome when added to P/C in MAP. This is the first report of P/C in MAP, which proved to have higher activity than anticipated, suggesting that similar to other disease settings, a relatively inexpensive taxane is an acceptable choice in MAP. A pharmaco-economic analysis is underway. Disclosure: T. Bekaii-Saab: Research Funding: Oncolytics Biotech; M.A. Villalona-Calero: Research Grant : Oncolytics Biotech. All other authors have declared no conflicts of interest.