A Randomized Phase II study of Reolysin in Patients with Previously Treated Advanced or Metatstatic Non Small Cell Lung Cancer (NSCLC) receiving Standard Salvage Chemotherapy – Canadian Cancer Trials Group IND 211.

e20512 Background: Despite advances associated with the use of targeted therapy, cytotoxic chemotherapy and immunotherapy the treatment of advanced NSCLC remains challenging. In this study we evaluated the effect of the oncolytic type 3 Dearing virus, Reolysin, in combination with standard salvage chemotherapy. Methods: This multicenter non-blinded phase II clinical trial randomized advanced stage refractory platinum doublet NSCLC patients to either docetaxel (squamous histology or pemetrexed pretreated) or to pemetrexed (non-squamous) plus or minus Reolysin. Results: No dose related toxicities were seen in a safety lead in group of patients in Arm A (N = 8) and Arm C (N = 6) allowing a total of 152 patients to be randomized as follows: Arm A: Pem (500mg/m2) IV plus Reo 4.5x1010 Day1-3 every 3 weeks; Arm B: Pem alone every 3 weeks; Arm C Doc (75mg/m2) IV plus Reo 4.5x1010Day1-3 every 3 weeks and Arm D: Doc alone every 3 weeks between January 2013 and August 2015. The arms were well balanced and at a median follow up of 16.5 months the median PFS was 2.96 (95% c.i. 2.56-4.17) and 2.83 (95% c.i. 2.50-3.98) months for Arms A/C and B/D, respectively. Response rate for all randomized patients was 14.3% (95% c.i. 7.4–24.1%) and 14.7 (95% c.i 7.6-24.7%) for Arms A/C and B/D, respectively (p = 0.96). The hazard ratio for survival of Arms A/C to B/D was 0.92 (0.63- 1.35, p = 0.9). Female gender PFS favoured Arms A/C vs B/D with a hazard ratio of 0.59 (95% c.i. 0.36-0.98). Further, post hoc analysis of PFS in selected EGFR/ERBB2/ERBB4/KRAS/NRAS/BRAF/PI3CA/PTEN/TP53 mutated patients was evaluated with only EGFR mut and p53 mutated pts trending to favoring the A/C arms HR 0.54 (95% c.i. 0.13-2.22) and HR 0.58 (95% c.i. 0.31-1.09). Conclusions:Reolysin was reasonably well tolerated at the dose and schedule administered with pemetrexed or docetaxel. No new safety signals were seen. It is of interest that females in the Reolysin containing arms did better than in the standard treatment arms and that in the post hoc subgroup analysis that EGFR mut and p53mut status was associated with a trend to improved PFS. Clinical trial information: NCT01708993.