Pfizer/Merck’s Bavencio Fails to Meet Primary Objective in Phase III JAVELIN Gastric 100 Study

PfizerMerck’s Bavencio Fails to Meet Primary Objective in Phase III JAVELIN Gastric 100 Study

Merck and Pfizer announced topline results of the Phase III JAVELIN Gastric 100 study evaluating Bavencio (avelumab) as first-line maintenance therapy following induction chemotherapy in patients with unresectable, locally advanced or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) cancer versus continuation of chemotherapy or best supportive care. While the study showed clinical activity, the primary endpoints were not reached. 

JAVELIN Gastric 100 was a multicenter, randomized, open-label trial investigating maintenance therapy with avelumab in patients with HER2-negative advanced (unresectable, locally advanced or metastatic) adenocarcinoma of the stomach or of the gastroesophageal junction (GEJ) who have not yet received chemotherapy for the treatment of metastatic or locally advanced disease, in an overall population unselected for PD-L1 expression. A total of 805 patients were enrolled to receive induction (initial) chemotherapy with oxaliplatin and either 5-fluorouracil (5-FU) or capecitabine for 12 weeks. Of these, 499 patients whose disease had not progressed at the end of the 12 weeks of chemotherapy treatment were randomly assigned to receive either avelumab as a maintenance treatment or continuation of the same chemotherapy regimen until disease progression. Patients unfit for further chemotherapy received best supportive care. The primary endpoints were overall survival in all randomized patients or in the PD-L1+ population (≥1%).

While the study showed clinical activity for avelumab in this setting, it did not meet the primary endpoints of superior overall survival compared with the standard of care in the overall intent-to-treat population (n=499) or the PD-L1–positive population (n=54).

The companies intend to conduct a detailed analysis of the Phase III JAVELIN Gastric 100 study, and share the findings with the scientific community.

About Bavencio (avelumab)

Bavencio is a human anti-programmed death ligand-1 (PD-L1) antibody. Bavencio has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, Bavencio has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models. 

Merck KGaA, Darmstadt, Germany and Pfizer entered into a strategic alliance to co-develop and co-commercialize Bavencio  in November 2014. 

Bavencio (avelumab) in combination with axitinib has been approved in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC). The U.S. FDA also granted accelerated approval for Bavencio for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. 

Bavencio is currently approved for patients with MCC in 50 countries globally.

About Gastric Cancer

Gastric cancer is the third most common cause of cancer death. The standard first-line option for patients with HER2-negative disease is chemotherapy, yet patients with advanced disease can experience resistance, leading to a poor prognosis. Over the past decade, there have been limited advancements in treatment, and the median overall survival for patients at the advanced stage is less than one year.