Abstract C70: A phase 2 study of intravenous administration of REOLYSIN® (reovirus type 3 dearing) in combination with paclitaxel (P) and carboplatin (C) in patients with squamous cell carcinoma of the lung.

Background: REOLYSIN is a unique, dearing strain oncolytic live virus which has demonstrated the ability to replicate in tumor cells with an activated RAS pathway. It has synergistic antitumor activity in combination with chemotherapy in both preclinical and clinical studies. Based on the promising activity of the combination of REOLYSIN with P/C in 2 trials in SCC of the head and neck, we elected to test this regimen in this Phase 2 trial in SCCLung. Methods: Goals of this single-arm, open-label phase II study were to determine, first, the objective response rate (ORR) and second, the 6-month progression-free survival (PFS) and the overall survival (OS) of patients with metastatic or recurrent squamous cell carcinoma of the lung, treated with REOLYSIN in combination with standard doses of P/C. The study had a two-stage design, with 19 patients in the first stage. The trial would be terminated if 3/19 or fewer patients obtained an objective response. If the trial continued to the second stage, a total of up to 36 patients would be studied. The primary endpoint wouldbe met if patients in both stages had an ORR of at least 35%. Eligible patients had ECOG PS 0-2, adequate organ function, and no prior systemic chemotherapy for their metastatic or recurrent disease. Prior adjuvant chemotherapy or chemo-XRT for treatment of primary disease was allowed, provided that ≥ 6 months had elapsed since the last chemotherapy. Treatment dosages were: P200 mg/m2 IV over 3 hours; carboplatin at AUC 6 mg/mL minute calculated using standard formula(s)and REOLYSIN 3x1010 TCID50IV over 1 hour daily for 5 days every 21 days. Results: 32 patients (20 males) entered the study and received at least one dose of study drug. Median age was 62 years (range 37-80)and all were Caucasian. 25evaluable patients received more than one cycle of therapy and a total of 125 cycles were administered in that group (per patient mean=5, median=6, range 2-12). The 7 non-evaluable patients received 1 cycle or less. Of the 25 evaluable patients who received more than one cycle, 12 (48%)had a PR, 10(40%) had stable disease (SD), and 3 (12%) had progressive disease (PD) for overall disease control(CR + PR + SD) in 22/25 (88%). Of 21 patients with >6 months follow-up, 7 (33.3%) have PFS of at least 6 months. The most common adverse events (AEs) seen were those expected with P/C—neutropenia 17 (9=Gr 3-4) and thrombocytopenia 15 (5=Gr 3-4) and those expected with REOLYSIN—fever 6 (1=Gr 3) and fatigue 11 (4=Gr 3). The AE profile of P/C therapy did not appear to be significantly altered by the addition of REOLYSIN. The only serious adverse eventreported as unexpected and related to study therapy was reversible Gr 2 elevation of creatinine (and increased BUN) which occurred 3 weeks after Cycle 8 in a 65-year-old woman. Conclusions:REOLYSIN in combination with P/C was well-tolerated in patients with recurrent/metastatic SCClung and the response results justify further studies. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C70. Citation Format: Alain C. Mita, Athanassios Argiris, Matt Coffey, George Gill, Monica Mita. A phase 2 study of intravenous administration of REOLYSIN® (reovirus type 3 dearing) in combination with paclitaxel (P) and carboplatin (C) in patients with squamous cell carcinoma of the lung. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C70.