Skip to main content
Premium Trial:

Request an Annual Quote

OncoMed Studying Vantictumab in HER2-Negative Breast Cancer; Exploring Predictive Biomarkers

Premium

OncoMed Pharmaceuticals this week announced that it has launched a Phase Ib trial to investigate the use of its Wnt pathway-targeting antibody vantictumab in combination with paclitaxel as a potential treatment for breast cancer.

The Phase Ib study is one of three trials for vantictumab that OncoMed is planning to launch by year end as part of a collaboration with Bayer Pharma. Researchers will also look for predictive response markers that could be used to identify best responders to vantictumab.

OncoMed is proceeding with Phase Ib studies after encouraging findings from a Phase Ia trial in which researchers used vantictumab to treat 29 patients with advanced and refractory solid tumors. The data, reported at a medical conference in September, showed that the drug was well tolerated up to a 15 mg/kg dose given every three weeks. Researchers reported the drug appeared to have activity in various cancers, including patients with neuroendocrine tumors.

"The Phase Ib trial in breast cancer is a dose-escalation and expansion trial of vantictumab in combination with weekly paclitaxel," OncoMed Chief Medical Officer Jakob Dupont told PGx Reporter.

In the trial, vantictumab plus weekly paclitaxel will be given to approximately 20 locally advanced or metastatic breast cancer patients with HER2-negative tumors in the first-, second-, and third-line setting. "The paclitaxel chemotherapy will be administered as per standard of care for weekly paclitaxel in metastatic breast cancer and vantictumab will be dose escalated in sequential dose-escalation cohorts of three to six patients until the maximum tolerated dose is defined for the combination," Dupont said.

The primary objective for researchers will be to evaluate the safety of the combination treatment and identify a dose for vantictumab that they can use in Phase II trials. Secondary objectives of the trial are to gauge the pharmacokinetics and pharmacodynamics of the drug, and the efficacy of the combination regimen. OncoMed will also collect tumor tissue from patients to explore predictive biomarker hypotheses about vantictumab's efficacy in molecularly-defined patient subsets.

Although OncoMed is exploring a personalized medicine strategy for vantictumab in breast cancer, the company isn't ready to publicly discuss the details of this effort yet. The company will also use a test to gauge the predictive biomarker of interest in study participants.

"We have not publicly disclosed the test or technologies that we are using to [assess] the predictive hypothesis but we plan to do so in future," Dupont said.

At a conference in October, researchers presented pharmacodynamic biomarker data from the Phase Ia trial. "Wnt pathway genes (e.g., AXIN2), and stem cell and differentiation genes (e.g., BMP8B, GFI1) were found to be regulated in hair follicles by vantictumab treatment," researchers from OncoMed and elsewhere reported in the poster presented at the meeting. "In tumors, vantictumab inhibited Wnt target (e.g., AXIN2, TCF4), stem cell, and EMT genes (HOXA2, ZEB2) and increased the expression of differentiation genes, including MUC4, MUC5B, and MUC20." These pharmacodynamic changes were observed at the lowest vantictumab doses, after one to two weeks of dosing.

If OncoMed's Phase Ib trials for vantictumab are successful, it could trigger further investments from partner Bayer in the clinical development program for the drug. "The clinical data from this and two other Phase Ib trials with vantictumab could potentially lead to an opt-in decision by Bayer to take vantictumab into later stage randomized clinical trials," OncoMed CEO Paul Hastings said in a statement.

OncoMed is focused on developing anti-cancer agents that interrogate biological pathways that help cancer stem cells survive and thereby drive tumor growth. The Wnt pathway is one such mechanism. In patient-derived xenograft models, vantictumab has reduced cancer stem cell frequency in different tumor types.

Vantictumab binds to so-called Frizzled receptors and blocks Wnt signaling. Frizzled receptors are proteins that play a role in cell proliferation, cell polarity, embryonic development, and other key functions. Researchers have found that vantictumab can bind to five of the 10 Frizzled receptors in the Wnt pathway.

Other than breast cancer, OncoMed is also studying vantictumab in combination with docetaxel in previously treated non-small cell lung cancer patients. OncoMed hasn't yet publicized the third indication it is pursuing for vantictumab.

The Phase Ib breast cancer study for vantictumab is currently open for enrollment and is slated for completion in about a year.

The Scan

Shape of Them All

According to BBC News, researchers have developed a protein structure database that includes much of the human proteome.

For Flu and More

The Wall Street Journal reports that several vaccine developers are working on mRNA-based vaccines for influenza.

To Boost Women

China's Ministry of Science and Technology aims to boost the number of female researchers through a new policy, reports the South China Morning Post.

Science Papers Describe Approach to Predict Chemotherapeutic Response, Role of Transcriptional Noise

In Science this week: neural network to predict chemotherapeutic response in cancer patients, and more.