Phase 2 Study of Intravenous Administration of Reovirus Serotype 3 - Dearing Strain (REOLYSIN®) in Combination With Paclitaxel and Carboplatin in Patients With Metastatic or Recurrent Non-Small Cell Lung Cancer Who Have KRAS or EGFR Activated Tumors
Reovirus Serotype 3 - Dearing Strain (REOLYSIN®) is a naturally occurring, ubiquitous,
non-enveloped human reovirus. Reovirus has been shown to replicate selectively in
Ras-transformed cells causing cell lysis. Activating mutations in ras or mutation in
oncogenes signaling through the ras pathway may occur in as many as 80% of human tumors. The
specificity of the reovirus for Ras-transformed cells, coupled with its relatively
nonpathogenic nature in humans, makes it an attractive anti-cancer therapy candidate.
Given the ability of reovirus to replicate and cause oncolysis in Ras-activated cells, the
high incidence of K-ras mutations in lung cancers, and the Ras-mediated activation often
encountered in EGFR-addicted tumors, the administration of REOLYSIN® in combination with
chemotherapy is expected to result in enhanced clinical benefit in non-small cell lung
cancer (NSCLC) patients with K-ras mutations and/or EGFR aberrant activation in their
tumors. Patients with de novo or acquired EGFR mutations in their tumors that confer
resistance to EGFR TKIs (e.g. T790) are expected to benefit as well. This is a single arm,
open-label, Phase 2 study of REOLYSIN® given intravenously with paclitaxel and carboplatin
every 3 weeks (21 days is defined as a cycle) in NSCLC patients with tumors driven by these
Paclitaxel at a dose of 175 mg/m2 will be given i.v. as a 3 hour infusion on Day 1 followed
by carboplatin given i.v. AUC 5 mg/mL•minute. REOLYSIN® will be given over 60 min on Day 1
(starting after completion of the carboplatin infusion), and on Days 2 - 5. The treatment
cycle will be repeated every 21 days.
Patients will receive 4 to 6 cycles of paclitaxel and carboplatin, at the treating
physician's discretion according to standard of practice, in conjunction with REOLYSIN®.
After completion of the 4 to 6 cycles of paclitaxel and carboplatin, REOLYSIN® may be
continued as monotherapy Days 1-5 of each 21 day cycle until there is evidence of disease
progression or unacceptable toxicity. Patients may continue to receive therapy under this
protocol, provided they have not experienced either progressive disease or unacceptable
drug-related toxicity that does not respond to either supportive care or dose reduction.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine the objective response rate (complete response (CR) + partial response (PR)) of the treatment regimen in the study population
For PR or CR, changes in tumor measurements must be confirmed 4 weeks after the criteria for response are first met.
Miguel Villalona, MD
Ohio State University
United States: Food and Drug Administration
|Georgetown University Medical Center||Washington, District of Columbia 20007|
|The Ohio State University Medical Center, James Cancer Hospital and Solove Research Institute||Columbus, Ohio 43210|