The objectives of the study were to define the safety profile and maximum tolerated dose of RAV12, to define the pharmacokinetics and describe preliminary efficacy.
Treatment with RAV12 demonstrated preliminary evidence of anti-tumor activity. One patient with refractory colorectal cancer experienced a partial remission with time to progression exceeding 8 months, and one patient with advanced pancreatic cancer had more than 50% reduction in the relevant tumor marker, CA19-9 and experienced disease stability for more than five months.
The two primary side effects observed were Infusion-associated abdominal discomfort and diarrhea, and elevated liver function tests. Both side effects appear related to CMax as they tended to appear early on after dosing and tended to resolve rapidly after dosing, and were ameliorated by fractionated dosing.
As a result of these findings, future development of RAV12 both as single agent and in combination with chemotherapy is planned for 2008. The recommended dose and schedule for Phase II clinical study of RAV12 is 0.75 mg/kg twice weekly.
George Schreiner, CEO of Raven Biotechnologies, said: “The study results demonstrate that a fractionated dosing regimen allows us to deliver RAV12 with an acceptable level of toxicity, while maintaining exposure that is associated with a tumor response. We are particularly encouraged to have seen a clinical response in one of the patients with advanced stage gastrointestinal cancer.”