On January 4, 2017 OncoMed Pharmaceuticals, Inc. (NASDAQ:OMED), a clinical-stage company focused on discovering and developing novel anti-cancer stem cell and immuno-oncology therapeutics, reported dosing of the first patient in a Phase 1b clinical trial of anti-DLL4/VEGF bispecific antibody (OMP-305B83) plus chemotherapy in patients with second-line metastatic colorectal cancer (Press release, OncoMed, JAN 4, 2017, View Source [SID1234517259]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The anti-DLL4/VEGF is the first antibody developed utilizing OncoMed’s BiMAb bispecific platform technology and is designed to have anti-cancer stem cell, immunomodulatory and anti-angiogenic activity. Thirty patients with metastatic colorectal cancer who have failed first-line treatment, typically bevicizumab plus FOLFOX (folinic acid, fluorouracil, oxaliplatin) chemotherapy, will receive second-line treatment in the Phase 1b multicenter, open-label dose escalation and expansion study of the anti-DLL4/VEGF bispecific antibody in combination with FOLFIRI (folinic acid, fluorouracil and irinotecan) chemotherapy. This trial is designed to determine the safety, preliminary efficacy, immunogenicity, pharmacokinetics and biomarker effects of the anti-DLL4/VEGF bispecific antibody plus FOLFIRI. A second Phase 1b study in patients with platinum resistant ovarian cancer is expected to begin enrolling patients soon.

"Metastatic colorectal cancer is an indication that we believe may benefit from the combined inhibition of DLL4 and VEGF plus chemotherapy," said Robert Stagg, Pharm.D., OncoMed’s Vice President, Clinical Research. "Anti-VEGF therapy plus 5-fluorouracil-based chemotherapy is currently approved in the treatment of second-line metastatic colorectal cancer, and this Phase 1b clinical trial is an opportunity to study the safety and preliminary efficacy of our anti-DLL4/VEGF bispecific antibody in combination with 5-fluorouracil-based chemotherapy and to observe if the multi-pronged mechanism of action may provide signs of enhanced activity."

In an ongoing Phase 1a dose escalation and expansion study of OncoMed’s anti-DLL4/VEGF bispecific antibody as a single agent, interim data was presented on 51 patients with previously treated advanced solid tumors who were treated in the dose escalation portion of the trial. Additional patients are currently being enrolled in the expansion phase of the study. Anti-DLL4/VEGF bispecific antibody was generally well tolerated with hypertension, headache and pulmonary hypertension being the most common drug related toxicities. Single-agent anti-tumor activity was observed: two of 46 evaluable patients had a partial response and 12 other patients had a reduction in their tumor volume. One of the two colorectal patients on study had a reduction in tumor volume.1

About anti-DLL4/VEGF Bispecific Antibody (OMP-305B83)
OncoMed’s anti-DLL4/VEGF bispecific antibody is designed to inhibit the function of both DLL4 and VEGF and thereby induce potent anti-tumor responses while mitigating certain angiogenic-related toxicities. It was developed utilizing OncoMed’s BiMAb bispecific platform technology, which enables the design of bispecific antibodies comparable to traditional monoclonal antibodies but possessing dual target-binding specificity.

In preclinical studies OncoMed’s anti-DLL4/VEGF bispecific antibody demonstrated robust in vivo anti-tumor efficacy across a range of solid tumor xenografts, including colon, ovarian, lung and pancreatic cancers, among others. Further, in preclinical studies dual inhibition of DLL4 and VEGF appears to exhibit synergistic anti-tumor activity at doses where blockade of either target alone elicited sub-optimal activity.