NCT02620423

Study of Pembrolizumab With REOLYSIN® and Chemotherapy in Patients With Advanced Pancreatic Adenocarcinoma

A Phase 1b Study of Pembrolizumab (KEYTRUDA®) in Combination With REOLYSIN® (Pelareorep) and Chemotherapy in Patients With Advanced Pancreatic Adenocarcinoma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 11 (actual)
• Sponsor: Oncolytics Biotech · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this Phase 1b study is to investigate whether intravenous administration of REOLYSIN® in combination with chemotherapy and pembrolizumab is effective and safe in the treatment of pancreatic adenocarcinoma.

Detailed description

Reovirus Serotype 3 - Dearing Strain (REOLYSIN®) is a naturally occurring, ubiquitous, non-enveloped human reovirus. It's primary mode of activity is to infect and selectively target tumors with activating Ras pathway mutations. Up to 70% of pancreatic cancers have activating Ras pathway mutations and/ or over-expressions. This is an open label, Phase 1b study of REOLYSIN® and chemotherapy in combination with pembrolizumab in patients with advanced (unresectable or metastatic) histologically confirmed pancreatic adenocarcinoma that progressed after (or did not tolerate) first-line therapy. It is thought that Reovirus when combined with chemotherapy would lead to increased viral replication and oncolysis preferentially in RAS activated tumors, with resulting immunogenic response than can be further enhanced by checkpoint inhibition using pembrolizumab. The study is designed to characterize the efficacy and safety of REOLYSIN® given intravenously in combination with one of the three chemotherapy backbone regimens, Gemcitabine, Irinotecan or Leucovorin/ 5-fluorouracil (5-FU), and pembrolizumab, the treatment cycle of which will be repeated every 3 weeks. It will follow a 3+3 design with no dose escalations. 3 patients will be initially enrolled. If no dose limiting toxicities (DLT) are observed, the cohort will be expanded. Provided patients do not develop intolerable toxicity (that does not respond to either supportive care or dose reduction) or clinically meaningful disease progression, treatment with additional cycles may be continued so long as patients experience clinical benefit in the judgement of the Investigator.

Conditions

• Pancreatic Adenocarcinoma

Interventions

Type	Name	Description
BIOLOGICAL	REOLYSIN®	4.5x10E10 TCID50 1 hour intravenous infusion, administered on Day 1 and 2 of a 21-day cycle
DRUG	Chemotherapy	Patients may be treated with one of three chemotherapy backbone regimens. The decision on the chemotherapy backbone is based on physician preference.This includes either: a) Gemcitabine or b) Irinotecan or c)Leucovorin followed by 5-fluorouracil
DRUG	Gemcitabine	1000 mg/m2 intravenous infusion over 30 minutes on Day 1 of a 21-day cycle or
DRUG	Irinotecan	125 mg/m2 intravenous infusion over 90 minutes on Day 1 of a 21-day cyle or
DRUG	Leucovorin	Leucovorin (LV) followed by 5-fluorouracil (5FU). LV 200 mg/m2 intravenous infusion over 2 hours on Day 1, 5FU 200 mg/m2 intravenous infusion bolus over 5-10 minutes on Day 1, followed by 5FU 1200 mg/m2 continuous intravenous infusion over 22 hours on Day 1 of a 21-day cycle
DRUG	5-fluorouracil	Leucovorin (LV) followed by 5-fluorouracil (5FU). LV 200 mg/m2 intravenous infusion over 2 hours on Day 1, 5FU 200 mg/m2 intravenous infusion bolus over 5-10 minutes on Day 1, followed by 5FU 1200 mg/m2 continuous intravenous infusion over 22 hours on Day 1 of a 21-day cycle
DRUG	Pembrolizumab	Pembrolizumab, 2 mg/kg intravenous infusion 30 minutes on Day 8 of a 21-day cycle

Timeline

• Start date: 2015-12-01
• Primary completion: 2018-03-01
• Completion: 2018-08-01
• First posted: 2015-12-03
• Last updated: 2018-09-13

Locations

1 site across 1 country: United States