NCI-8601 is a two-arm randomized Phase II study of carboplatin and paclitaxel plus REOLYSIN® versus carboplatin and paclitaxel alone in the first line treatment of patients with recurrent or metastatic pancreatic cancer. Patients were randomized to receive either carboplatin, paclitaxel and REOLYSIN® (test arm) or carboplatin and paclitaxel alone (control arm). Patients in both arms received treatment every three weeks (21-day cycles) and standard intravenous doses of paclitaxel and carboplatin on day one only. In the test arm, patients also received intravenous REOLYSIN® at a dose of 3×1010 TCID50 on days one through five. Tumour response was assessed by computed tomography (CT) scan and conducted every eight weeks. Patients who progressed on carboplatin and paclitaxel (control arm) had REOLYSIN® added to their treatment regimens (crossover arm). If patients experienced significant toxicity related to carboplatin and/or paclitaxel, they could continue with single agent REOLYSIN®. Seventy-three patients were enrolled. The primary objective is progression-free survival. Secondary objectives include toxicity, overall response rate, and overall survival. Other objectives include the measurement of immunologic markers that may correlate with other study outcomes, and examination of whether a relationship may exist between Ras pathway activation and response.
Initial findings from the study were presented by the Company in September 2014. In the overall patient population, the median progression free survival for the control arm was 5.16 months (95% confidence interval (CI) = 2.267 to 6.176) versus 5.26 months for the test arm (95% CI = 3.187 to 6.307). However, of the sixty patients whose KRAS status (mutant versus wild type) could be determined during screening, 44 (73%) had mutations in the KRAS gene (n = 23 in the control arm, n = 21 in the test arm). In addition, median progression-free survival in the test arm was 5.72 months (95% CI = 3.187 to 6.767) versus 4.11 months in the control arm (95% CI = 1.938 to 6.176), translating into a 1.61 month (39%) improvement in median progression-free survival in the test arm versus the control arm. This is the first randomized clinical evidence that KRAS status could potentially be a predictive biomarker that influences a patient’s clinical outcomes when treated with a drug regime that includes REOLYSIN®.
The Company announced updated results from the study in April 2016, with an intent-to-treat analysis showing a statistically significant increase in two-year overall survival (“OS”) in patients who were treated with REOLYSIN®, whether in the test arm or upon crossing over subsequent to progression in the control arm:
|Arm||Median OS (months)||1-year OS
|Control (n = 20)||6.57||25.0||0||0|
|Test (n = 36)||7.33||29.6||17.7||8.87|
|Cross-Over (n = 16)||10.97||25.0||12.5||6.25|
|Combined Test and Cross-Over
(n = 52)
Source: NCI Clinical Trial Summary: Response Information Report
The analysis showed a statistically significantly higher percentage of patients surviving two years in the test arm versus the control arm (p = 0.001), the crossover arm versus the control arm (p = 0.03) and the test plus crossover arms versus the control arm (p = 0.0004). At the time of the data cut off (January 19, 2016), there were five survivors on study in the test arm, and one survivor on study in the crossover arm. As a result, the two- and three-year survival for the arms may continue to evolve.
The study is being sponsored and conducted by the US National Cancer Institute (NCI). Final data from the study remains pending.