Navigation Links
Raven Announces Phase 1 Clinical Trial Results of RAV12 Therapeutic Antibody for Treatment of Adenocarcinomas
Date:11/19/2007

- Study Results Determine Phase 2 Dosing Regimen -

SOUTH SAN FRANCISCO, Calif., Nov. 19 /PRNewswire/ -- Raven biotechnologies, inc., a privately held company focused on the development of monoclonal antibody therapeutics (MAbs) for cancer, today announced updated results from an ongoing Phase 1/2a open-label, dose escalation clinical trial of RAV12, its lead therapeutic antibody in development for the treatment of adenocarcinomas. 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.

"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," said George Schreiner, M.D., Ph.D., chief executive officer of Raven biotechnologies. "We are particularly encouraged to have seen a clinical response in one of the patients with advanced stage gastrointestinal cancer. These findings further demonstrate the potential therapeutic value of RAV12."

Study Design

The phase 1 dose-escalation safety and pharmacokinetics (PK) trial was initiated in December 2004 in patients with recurrent adenocarcinoma who had received 1 to 3 prior treatment courses. RAV12 was administered initially four times weekly, then by fractionated dosing two or three times weekly. Thirty-three patients were treated in the dose escalation segment of the trial. Three cohorts were given a weekly dose of 0.3 mg/kg, 1.0 mg/kg, and 1.5 mg/kg, and three cohorts received fractionated dose schedules of 0.5 mg/kg twice weekly, 0.75 mg/kg twice weekly, and 0.5 mg/kg thrice weekly.

Patients all had confirmed adenocarcinoma of gastrointestinal origin or of other origin if they positively expressed the RAAG12 antigen. The majority of patients had colorectal, gastroesophageal, or pancreatic cancer. Patient responses were evaluated on day 42.

Study Results

RAV12 was moderately well-tolerated with fractionated dosing that allowed delivery of an "effective dose" (i.e. 1.5 mg/kg total dose over one week time) as 0.75 mg/kg twice weekly. 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.

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 a > 50% reduction in the relevant tumor marker, CA19-9 and experienced disease stability for more than five months.

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 2 clinical study of RAV12 is 0.75 mg/kg twice weekly.

About RAV12

RAV12 is a novel, chimeric monoclonal antibody which is directed against a primate-specific glycotope (sugar structure) that is widely displayed on the surfaces of tumor cells, particularly those of gastrointestinal origin (gastroesophageal, pancreatic, colorectal cancers). Preclinical studies have demonstrated that RAV12 may kill tumor cells in a number of ways: first, the antibody is directly cytotoxic to a human colon cancer cell line in vitro through induction of oncotic cell death, a form of cell death characterized by cell and organelle swelling and loss of membrane integrity; second, the antibody mediates antibody-dependent cellular cytotoxicity; third, the antibody mediates complement dependent cell killing; and finally, the antibody alters cellular signaling required for cell survival. RAV12 is highly efficacious in human colon, gastric, and pancreatic tumor xenograft models in vivo and has been found to be well tolerated in repeat dose primate toxicology studies.

About GI Cancers

Adenocarcinomas are malignant tumors of the epithelial cells that line glands or viscera. They typically spread by way of the circulatory or lymphatic systems and are poorly treated after metastatic spread. More than 90 percent of colon, stomach and pancreatic tumor specimens express the RAV12 defined antigen, RAAG12. Adenocarcinomas arising elsewhere, such as breast, endometrial, ovarian, lung and prostate, display the antigen to varying degrees.

About Raven

Raven biotechnologies, inc. (http://www.ravenbio.com) is a privately held biotechnology company focused on the development of monoclonal antibody therapeutics for treating cancer. Raven's lead product candidate, RAV12, targets adenocarcinomas and is in clinical development for the treatment of gastrointestinal and other cancers. Raven's discovery process simultaneously identifies cell-surface drug targets and the antibody therapeutics to regulate them. Our focus on biological function allows us to rapidly identify novel target antigens and therapeutic candidates in their native configuration in the intact cell membrane. Our integrated approach is based on proprietary methods for optimizing the production of MAbs targeting cell-surface proteins, including the use of human tissue-specific progenitor and tumor stem cell lines developed at Raven.

To date Raven has identified multiple candidate therapeutic MAbs for many cancer indications including lung, colon, pancreatic, prostate, breast, brain, and ovarian cancer.


'/>"/>
SOURCE Raven biotechnologies, inc.
Copyright©2007 PR Newswire.
All rights reserved

Related medicine technology :

1. Cadence Pharmaceuticals Completes Enrollment of Pivotal Phase III Trial for Intravenous Acetaminophen Ahead of Schedule
2. Dendreon Announces Publication of Phase 1 Study Highlighting Immunologic and Clinical Activity of Lapuleucel-T (Neuvenge(R)) in Advanced Breast Cancer Patients
3. EDAP Announces Launch of Clinical Study Combining HIFU and Chemotherapy for Localized Aggressive High Risk Prostate Cancer
4. Cephalon Announces Positive Results from a Pivotal Study of FENTORA in Opioid-tolerant Patients with Non-cancer Breakthrough Pain
5. ADVENTRX Announces Fast Track Designation Granted By the FDA For CoFactor For the Treatment of Metastatic Colorectal Cancer
6. DOV Pharmaceutical, Inc. Announces Successful Phase Ib Results for DOV 21,947
7. Phosphagenics Announces Positive Phase 1b Transdermal Insulin Clinical Trial Results
8. Xenomics Announces Implementation of its First Diagnostic Test for Acute Myeloid Leukemia Into Clinical Practice
9. Emisphere Technologies, Inc. Announces 2007 Second Quarter Financial Results
10. Amicus Therapeutics Announces Second Quarter 2007 Financial Results
11. Genta Incorporated Announces Second Quarter 2007 Financial Results and Corporate Highlights
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:9/19/2017)...   ZirMed Inc ., a recognized leader in cloud-based ... has been ranked #1 by its users for the seventh ... User Survey. ZirMed was recognized as the top-ranked end-to-end revenue ... centers over 200 beds and holds one of the longest ... history. ...
(Date:9/13/2017)... has been named the official orthopedic and sports medicine ... 2018 College Football Playoff (CFP) National Championship to be played ... Atlanta, Georgia . OrthoAtlanta is proud to be ... many activities leading up to, and including the national championship ... OrthoAtlanta serves ...
(Date:9/12/2017)...  ValGenesis Inc., the global leader in Enterprise ... announce the appointment of Dr. Ajaz Hussain ... Directors and Chairman of Advisory Board beginning September ... to manage their entire validation lifecycle process electronically ... process. Furthermore, ValGenesis VLMS enables rigorous compliance, helps ...
Breaking Medicine Technology:
(Date:10/12/2017)... San Francisco, CA (PRWEB) , ... October 12, ... ... and Dr. Cheng, are now treating sleep apnea using cutting-edge Oventus ... sleep apnea, a serious sleep disorder characterized by frequent cessation in breathing. Oral ...
(Date:10/12/2017)... ... October 12, 2017 , ... The company has ... today’s consumer and regulatory authorities worldwide. From Children’s to Adults 50+, every formula ... the highest standard. , These products are also: Gluten Free, Non-GMO, Vegan, ...
(Date:10/12/2017)... ... October 12, 2017 , ... The American College of Medical Informatics (ACMI) will ... during the Opening Session of AMIA’s Annual Symposium in Washington, D.C. AMIA’s Annual ... F. Collen, a pioneer in the field of medical informatics, this prestigious award is ...
(Date:10/12/2017)... ... October 12, 2017 , ... ... system that we intend to develop to enable prevention of a major side ... severe hearing loss, especially in pediatric patients. For cisplatin, hearing loss is FDA ...
(Date:10/12/2017)... ... October 12, 2017 , ... HMP , a leader in healthcare events ... Magazine Eddie Digital Award for ‘Best B-to-B Healthcare Website.’ Winners were announced during the ... The annual award competition recognizes editorial and design excellence across a range of sectors. ...
Breaking Medicine News(10 mins):