Eli Lilly and Company has announced that the REGARD trial, a phase III study of ramucirumab (IMC-1121B) in patients with metastatic gastric cancer, met its primary endpoint of improved overall survival and also showed prolonged progression-free survival. This trial is the first phase III data read-out for ramucirumab.

The REGARD trial compared ramucirumab and best supportive care to placebo and best supportive care as a second-line treatment in patients with metastatic gastric and gastroesophageal junction cancers. The most frequent adverse reaction (any grade) occurring at a higher rate on the ramucirumab arm was hypertension (12 per cent). Other adverse reactions ( > five per cent) occurring at a higher rate on the ramucirumab arm compared to the placebo arm were diarrhea and headache.

"We are pleased with this data of ramucirumab used as monotherapy in a second-line setting in this difficult-to-treat disease. It reinforces our confidence in the ramucirumab development program, in which we currently have six phase III studies ongoing in five tumour types — breast, colorectal, gastric, hepatocellular and lung cancer," said Richard Gaynor, MD, vice president, product development and medical affairs for Lilly Oncology.

REGARD is one of two ramucirumab phase III studies in gastric cancer. RAINBOW, a phase III trial of ramucirumab in combination with paclitaxel, completed patient enrollment last month.

Lilly plans to present data from the REGARD trial at an upcoming scientific meeting and will discuss submission plans with regulatory authorities.

The REGARD trial is a phase III randomized, double-blinded study of ramucirumab and best supportive care (BSC) versus placebo and BSC in the treatment of metastatic gastric or gastroesophageal junction adenocarcinoma following disease progression on first-line platinum- or fluoropyrimidine-containing combination therapy. The primary endpoint of the REGARD trial is overall survival and secondary endpoints include: progression-free survival; proportion of participants who are progression-free at week 12; proportion of participants with objective response, or objective response rate; duration of response; and safety.

The RAINBOW trial is a phase III study of ramucirumab and paclitaxel compared to placebo and paclitaxel as a second-line treatment in patients with metastatic gastric cancer (including adenocarcinomas of the gastroesophageal junction), refractory to or progressive after first-line therapy with platinum and fluoropyrimidine. The primary endpoint of the RAINBOW trial is overall survival and secondary endpoints include: progression-free survival; time to progressive disease; best overall response; objective response; and safety.

Ramucirumab is a fully human IgG1 monoclonal antibody receptor antagonist designed to bind  the extracellular domain of vascular endothelial growth factor (VEGF) receptor-2, thereby blocking the interaction of VEGF ligands (VEGF-A, VEGF-C, and VEGF-D) and inhibiting receptor activation. VEGF receptor-2 is considered a primary mediator of angiogenesis. When activated by VEGF ligands, VEGF receptor-2 promotes endothelial cell proliferation and survival, migration, and vascular permeability.

Ramucirumab, which Lilly gained through its 2008 acquisition of ImClone Systems, is being investigated in clinical trials as monotherapy and in combination with other anticancer therapies for the treatment of multiple types of cancer. It is in late-stage clinical evaluation for the treatment of breast, colorectal, gastric, hepatocellular and lung cancer.

Gastric cancer is fourth most common cancer in the world, it is a disease in which cancer cells form in the lining of the stomach. It develops slowly, usually over many years and often goes undetected. As the stomach cancer advances, it can travel through the bloodstream and spread to organs such as the liver, lungs and bones.