Presentation Title: A Study of REOLYSIN in Combination with Gemcitabine in Patients with Advanced Pancreatic Adenocarcinoma
Location: West Hall, Level One, Moscone Center West
Poster Board Number: B55
Author Block: Monica M. Mita1, Yubao Wang2, John Sarantopoulos1, Sushma Vemulapalli1, Benjamin George3, Alain Mita1, Mattew Coffey4, George Gill5, Devaligam Mahaligam1. 1Cancer Therapy and Research Center at UTHSCSA, San Antonio, TX; 2Cancer Therapy and Reserach Center, San Antonio, TX; 3Brooke Army Medical Center, San Antonio, TX; 4Oncolytics Biothech, Calgary, AB, Canada; 5Oncolytics Biotech, Calgary, AB, Canada
Abstract Body: Background: Pancreatic cancer (Pca) continues to have a dismal prognosis and very little progress has been made in finding new efficacious treatments. Oncolytic viruses have demonstrated cytotoxic effect in several tumor xenografts, particularly in cells with RAS pathway activation. REOLYSIN (Reovirus serotype 3) has shown extensive antitumor activity in preclinical models, as well as synergistic activity with cytotoxics including gemcitabine in various cancers. Several phase 1 and 2 clinical trials demonstrated tolerability and promising activity of REOLYSIN administered as a single agent in patients with solid tumors. Due to the high frequency of Kras pathway activation in Pca, we hypothesized that REOLYSIN may enhance the anticancer activity of chemotherapy in this tumor type. Therefore, this study was initiated to test the safety and efficacy of a combination of REOLYSIN with gemcitabine in previously untreated patients with Pca.
Methods: Patients with diagnosis of chemotherapy-naïve, surgically unresectable or metastatic Pca are eligible for the study. The primary objective is Clinical Benefit Rate (CBR=CR+PR+SD>12 weeks).
Secondary objectives include progression-free survival (PFS), toxicity, tolerability as well as pharmacokinetics (PK) and pharmacodynamics (PD). Patients are treated with gemcitabine at 800 mg/m2 day 1 and 8, and REOLYSIN administered IV at day 1, 2 and 8, 9. Tumor assessment is performed every 2 cycles (6 weeks). A two stage design is used for this study. In stage 1 at least 3/17 patients must achieve CBR in order to proceed to stage 2.
Results: Fourteen patients were enrolled in the study and 10 are evaluable for efficacy. Age ranged from 48 to 82 years, mean 67 years. All patients except one reported symptomatic improvement. No CR were reported.
Two patients have SD for =36 weeks and one patient continues on study with SD at 39 weeks.
An additional patient had an unconfirmed PR of less than 6 weeks.
Six patients had SD = 12 weeks.
The treatment was well tolerated with common non-hematological toxicities including grade 1 fever, chills, nausea and vomiting. Only two patients had grade 3 neutropenia lasting 1-2 days. No other grade 3 toxicities were seen.
Conclusion: The endpoint for the first stage of the study (=3 CBR in the first 17 patients) has been reached and therefore enrollment will continue. REOLYSIN in combination with gemcitabine has demonstrated clinical benefit in patients with unresectable Pca with a tolerable toxicity profile.
Presentation Title: A phase II study of intravenous wild-type reovirus (Reolysin®) in combination with paclitaxel plus carboplatin in patients with platinum refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck
Location: West Hall, Level One, Moscone Center West
Poster Board Number: C22
Author Block: Anand B. Karnad1, Missak Haigentz2, Tracy Miley1, Matt Coffey3, George Gill3, Monica Mita1. 1CTRC, UT Health Science Center, San Antonio, TX; 2Montefiore Medical Center, Bronx, NY; 3Oncolytics Biotech Inc., Calgary, AB, Canada
Abstract Body: Purpose: REOLYSIN® (Reovirus serotype 3) is a Dearing strain, naturally occurring ubiquitous human reovirus. In transformed cells with activated RAS pathway, this reovirus causes preferential lysis due to the inhibition of RNA-activated protein kinase (PKR) in these cells. In a phase-I dose escalation trial three of six patients with squamous cell cancer of the head and neck showed significant responses in combination with chemotherapy leading to the design of this phase-II study.
Methods: A single arm, open-label, phase-II study of REOLYSIN 3 X 1010 TCID50 given intravenously Days 1-5, with paclitaxel (175 mg/m2) and carboplatin (AUC 5) on Day-1 every three weeks was conducted in patients with platinum-refractory recurrent and/or metastatic squamous cell cancers of the oral cavity, larynx, or pharynx.
The primary end point was to determine the objective response rate (CR + PR) of the treatment regimen in the study population. Secondary objectives included the determination of disease control rate (CR + PR + SD) and the safety and tolerability of the treatment regimen. Patients were required to have measurable disease and evaluation of tumor status was conducted at baseline and every other cycle.
Results: Since September 2008, 14 patients age 29-61 (median 54) were enrolled and received a total of 57 cycles (range 1-10). Thirteen of 14 patients were ECOG performance status 0 or 1 and 1 was ECOG 2.
All patients were platinum-refractory and received other prior chemotherapy, radiotherapy, or combinations for their metastatic or recurrent disease. Ten of 14 patients received prior treatment with taxanes. Sites of disease included larynx (3), oral cavity (6), and pharynx (4), and other site (1).
Side effects were mild to moderate (Grade 1-2) including constitutional symptoms, fever, chills, and fatigue. Grade-3 toxicities included hypokalemia (2 patients), fatigue (1), nausea (1), and AST elevation (1). Hematological side effects included Gr-4 neutropenia in 1 patient, Gr-3 neutropenia in 5 patients, and Gr-3 anemia in 3 patients.
Thirteen patients were evaluable for response. Four partial responses were seen for an objective response rate of 31%.
Two patients had SD for =12 weeks for a disease control rate of 46%.
Two of the 4 patients with PR and both patients with SD had received prior treatment with taxanes.
Conclusion: REOLYSIN in combination with paclitaxel and carboplatin showed significant activity in patients with platinum-refractory head and neck cancer. An international, randomized, double-blind Phase-III trial of the combination for this target population is under way.
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