The University of Kentucky Markey Cancer Center has treated the first patient in the U.S. with a new immunotherapy for small cell lung cancer, offering hope for patients whose cancers have stopped responding to other treatments.
UK Markey Cancer Center is the first site in the country to open a clinical trial for ZG006 (Alveltamig), an experimental drug that works by connecting disease-fighting T cells to cancer cells, allowing the body's immune system to attack the cancer. The first patient was treated in late October under the direction of Markey Cancer Center medical oncologist Zhonglin Hao, M.D., Ph.D.
ZG006 has a different structure than tarlatamab, another immunotherapy that was approved by the Food and Drug Administration in 2024 to treat people with small cell lung cancer whose disease had worsened with standard chemotherapy and immunotherapy. Known as a bispecific T-cell engager, tarlatamab uses two arms to connect cancer cells to T cells. As a trispecific engager, ZG006 has three arms - two to grab cancer cells much tighter and one to grab T cells.
"This is the next step forward in T-cell engager therapy for small cell lung cancer," said Hao, lead investigator for the trial, co-director of Markey's Thoracic Oncology Program and medical director of Markey's Clinical Research Office.
"We're testing a newer version of tarlatamab that has a stronger ability to connect cancer cells with immune cells. This trial will explore whether that enhanced design can help more patients respond to treatment or give those who've tried tarlatamab another option."
The trial also addresses an unmet need for patients with small cell lung cancer, which is usually diagnosed in advanced stages. Patients may respond to chemotherapy and radiation at first, but the cancer often returns quickly. Immunotherapies like ZG006 represent a newer treatment approach when standard therapies fail.
Patients receiving the treatment are closely monitored for potential side effects. The first patient treated at Markey experienced no side effects from the initial dose and returned two weeks later for a second treatment, which was also well-tolerated.
Hao said the immunotherapy is also potentially effective in treating brain metastases, which is common in small cell lung cancer and typically requires whole-brain radiation. By helping to provide better control of the systemic disease, immunotherapy may reduce or eliminate the need for brain radiation therapy, which can cause cognitive problems and other side effects including fatigue and hair loss.
Access to cutting-edge care in Kentucky
The Phase 1 trial is the first for ZG006 in the U.S., following a trial in China that showed the drug was well-tolerated among patients. The U.S. trial will enroll patients at six sites, with Markey being the first to open and treat a patient. Other sites, including Case Comprehensive Cancer Center, are preparing to open.
Markey's selection as the first U.S. site stems from its status as a National Cancer Institute-designated Comprehensive Cancer Center - one of just 57 in the nation. This designation allows Markey to offer patients access to trials that test the newest treatments before they become widely available.
"We want Kentuckians to be among the first to benefit from this newer drug," Hao said. "Clinical trials represent the future of cancer care. When patients participate in trials at Markey, they're getting access to tomorrow's treatments today."
