Athenex, Inc. announced a new collaboration to conduct a phase 1b study that will evaluate the safety and tolerability of oraxol, Athenex’s oral form of paclitaxel, in combination with Eli Lilly and company’s Cyramza (ramucirumab), a vascular endothelial growth factor (VEGF) receptor 2 antagonist, in patients with advanced gastric (stomach) and esophageal cancer.

Patient enrollment, currently expected to start in 2017, is planned at sites in the US and Asia. Athenex will be the sponsor of the clinical trial and Lilly will supply Cyramza.

Dr. Rudolf Kwan, Athenex’s chief medical officer, commented, “A major component of cancer treatment consists of intravenous chemotherapy. Many oncologists are currently limited by the amount of standard intravenous chemotherapy a patient can tolerate. Oraxol is the first drug candidate from an innovative technology platform which enables the oral administration of a chemotherapy drug usually administered by the intravenous route (i.e., paclitaxel). The effect of the compound is limited to the intestinal cells, as it is not significantly absorbed in humans. Oral dosing of paclitaxel potentially provides longer drug exposure over a target drug concentration and may offer the opportunity for chronic chemotherapy, which will be evaluated for increased efficacy.”

Oraxol is also being evaluated in a phase 3 metastatic breast cancer trial in a head-to-head comparison against intravenous paclitaxel. An open-label phase 2 study with oraxol as a monotherapy in advanced gastric cancer patients reported median overall survival of 10.7 months.

Cyramza is approved in the U.S. for use as a single agent or in combination with paclitaxel as a treatment for people with advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose cancer has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy.

Oraxol includes a combination of the oral absorption molecule, HM30181A, which is a P-glycoprotein (P-gp) pump inhibitor, and an oral form of paclitaxel. Suppression of the P-gp pump in the gastrointestinal tract allows certain compounds (such as paclitaxel), which would normally be effluxed back into the gastrointestinal tract and excreted, to enter the bloodstream and be bioavailable via oral administration. Importantly, HM30181A is a P-gp inhibitor that is not systemically absorbed. The current lead clinical phase products include an oral formulation of paclitaxel and an oral formulation of irinotecan, which are both in multiple clinical studies globally.

In the US, Cyramza (ramucirumab) is approved for use as a single agent or in combination with paclitaxel as a treatment for people with advanced or metastatic gastric (stomach) or gastroesophageal junction (GEJ) adenocarcinoma whose cancer has progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy. It is also approved in combination with docetaxel as a treatment for people with metastatic non-small cell lung cancer (NSCLC) whose cancer has progressed on or after platinum-based chemotherapy. Additionally, it is approved with FOLFIRI as a treatment for people with metastatic colorectal cancer (mCRC) whose cancer has progressed on or after therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.

There are several additional studies underway or planned to investigate Cyramza as a single agent and in combination with other anti-cancer therapies for the treatment of multiple tumor types. This broad global development program has enrolled more than 10,000 patients across more than 70 trials of Cyramza worldwide.

Cyramza is an antiangiogenic therapy. It is a vascular endothelial growth factor (VEGF) receptor 2 antagonist that specifically binds and blocks activation of VEGF receptor 2 by blocking the binding of VEGF receptor ligands VEGF-A, VEGF-C, and VEGF-D. Cyramza inhibited angiogenesis in an in vivo animal model.

The American Cancer Society estimates that 26,370 cases of gastric cancer will be diagnosed in the U.S. in 2016 (16,480 men and 9,890 women) and 10,730 people will die from this type of cancer (6,540 men and 4,190 women). Gastric cancer is much more common in other parts of the world, particularly in the Far East and less developed countries. It is the third leading cause of cancer-related deaths globally.

Cyramza is a trademark owned by or licensed to Eli Lilly and Company, its subsidiaries, or affiliates.