The national trial is being led by Dan P. Zandberg, MD, assistant professor of medicine at the University of Maryland School of Medicine and a medical oncologist specializing in head and neck cancers at UMGCC. The Greenebaum Cancer Center is currently the only trial site and is actively recruiting participants.
“When surgery isn’t possible for patients with locally recurrent squamous cell carcinoma of the head and neck, unfortunately, prognosis is generally poor, and newer more effective treatments are greatly needed.” says Dr. Zandberg. “MK-3475 has shown promise for treating head and neck cancers in clinical trials, and it’s our hope that it will prove to be even more effective against this type of cancer when given in combination with radiation.”
MK-3475 is one in a promising new class of immunotherapy cancer drugs that work by activating a patient’s own immune system against the tumor. Cancer cells thrive in part by suppressing the immune system so the immune system cannot attack the tumor. One important way the immune system is suppressed is by the interaction between PD-L1 on cancer cells and PD-1 on T cells—a type of white blood cell that is part of the immune system. PD-L1 (Programmed death ligand 1) is expressed by cancer cells and binds to PD-1 (Programmed death 1) on T cells, causing them to stop attacking the cancer. MK-3475 is a man-made antibody against PD-1 and blocks this interaction, allowing the T cells to continue to attack the cancer.
MK-3475 is approved by the U.S. Food and Drug Administration for treatment of advanced melanoma. It is being tested by its maker, pharmaceutical company Merck, for treatment of multiple different cancers including head and neck, kidney and lung cancer. In head and neck cancer preliminary efficacy has led to the development of a larger phase III trial for patients with advanced squamous cell carcinoma of the head and neck.
The UMGCC trial is the first to use MK-3475 in combination with radiation therapy to treat any type of cancer. By combining the drug with radiation, which is known to stimulate the immune system, researchers believe that, in addition to its local effects against the tumor, the radiation will increase the efficacy of MK-3475 and this synergy will result in improved outcomes for patients with inoperable localized recurrence of their head and neck cancer. Merck is providing the drug and funding for the trial.
The vast majority of cancers in the head and neck are squamous cell carcinomas. When patients are first diagnosed, treatment is typically up-front surgery or combined radiation and chemotherapy. Patients who undergo up-front surgery may receive radiation or combined radiation and chemotherapy after the surgery. Thus a significant amount of patients receive radiation as part of their initial therapy. If these patients recur without evidence of distant metastatic disease (cancer spreading beyond the head and neck) and surgical resection is not an option, they are typically treated with radiation again (reirradiation) combined with chemotherapy. Improved outcomes are needed for these patients, as unfortunately, the median progression-free survival is only 7-8 months. The primary endpoint of the trial is to determine if progression-free survival is extended by treatment with reirradiation and MK-3475.
Forty-eight patients will be recruited for the trial. All patients will receive radiation twice per day for five weeks with MK-3475 given intravenously every three weeks starting on the first day of radiation. MK-3475 will be continued for an additional three months following the completion of reirradiation. Patients will then be evaluated for response in their tumor. If there is a complete response, MK-3475 will be stopped and the patient will be followed to see if the tumor recurs. If there is a partial response or stable disease, the patient will continue being treated with MK-3475 as long as the tumor continues to respond or stay stable in size. If the tumor progresses, treatment with MK-3475 will be discontinued. Toxicity will be monitored closely during this trial.
To learn more about participating in this trial, read the frequently asked questions on the UMGCC website.