Memorial Sloan Kettering Cancer Center announced the launch of a Phase 2 study led by Yelena Y. Janjigian and Smita Joshi, which is evaluating the use of Nivolumab immunotherapy plus FOLFOX and Regorafenib in patients with HER2-negative metastatic esophagogastric cancer. The hypothesis—that the combination of chemotherapy, PD-1 blocker and tyrosine kinase inhibitor can help esophagus cancer patients to better outcomes. The study team hopes for 6-month progression free survival based on the RECIST 1.1 guidelines.
What is metastatic esophagogastric cancer?
Known as Esophageal cancer, this cancer occurs in the esophagus, that long, hollow tube that runs from the throat to the stomach. The body attribute helps the person move food from the back of the throat to the stomach to be digested.
This form of cancer typically initiates in the cells that line the inside of the esophagus and can occur anywhere along the esophagus. Typically men are impacted more than women. This cancer represents the sixth most common cause of cancer fatalities around the world. Particular incidence rates may depend on location, as in some regions of the world rates are higher than others. It is suspected that tobacco and alcohol use can contribute as well as some nutritional habits and obesity.
What is the purpose of this study?
Sponsored by Memorial Sloan Kettering in collaboration with pharma companies Bristol Myers Squibb and Bayer, the study (NCT04757363) centers on whether the combining of nivolumab, FOLFOX and regorafenib may be safe and effective for those patients with HER2-negative metastatic esophagogastric cancer.
What is the study hypothesis?
The study researchers think that combining nivolumab, FOLFOX, and regorafenib may be a more effective treatment for HER2-negative metastatic esophagogastric cancer than the usual chemotherapy treatment(s) alone.
What are the drugs involved?
The sponsors are using multiple drugs in this study, including FOLFOX, a combination of three standard chemotherapy drugs including leucovorin, 5-fluorouracil, and oxaliplatin. These drugs work by damaging the DNA in caner cells, which can act to impede cancerous cell growth. FOLFOX is already in use for this cancer. Combining it with the other two is considered investigational.
An antibody, that is much like the proteins generated by the immune system to protect the body from harm, Nivolumab (OPDIVO) serves to block the protein PD-1 (programmed cell death receptor-1) that often serves as a brake on the immune system. Hence, blocking this protein is akin to releasing the brakes, so that the immune system can be mobilized to target cancer cells and hopefully terminate them. Nivolumab is given via intravenous administration.
While Regorafenib (Stivarga) is a tyrosine kinase inhibitor (TKI) that targets the tyrosine kinase protein found in or on the surfacer of cancer cells that cells need to not only grow but to survive. The hypothesis here is that the drugs help block the protein and hence inhibit cancer cells from growing, or at least slow down the growth of the cells and hopefully contribute to the shrinking of such cells. This drug is given orally.
Many of these cancer studies have complex protocols with extensive inclusion and exclusion criteria. In this case the following criteria are required: 1) the patient must have HER2-negative metastatic esophagogastric cancer; 2) patients may not have received prior chemotherapy for metastatic disease, nor previous immunotherapy or regorafenib; 3) patients must be physically well enough that they are fully ambulatory, capable of self-care, and capable of all but physically strenuous activities. They must be 18 and up.
Yelena Y. Janjigian, MD, Chief, Gastrointestinal Oncology Service
Call to Action: If you are based in the New York area and interested in this study, contact Dr. Yelena Janjigian at 646-888-4186.