First U.S. Patient Treated With Alveltamig for Small Cell Lung Cancer

Patients with small cell lung cancer are now being treated with a new experimental immunotherapy in the U.S. after the University of Kentucky Markey Cancer Center became the first site in the country to open a clinical trial of Alveltamig (ZG006), with the first patient receiving the therapy in late October under the direction of medical oncologist Dr. Zhonglin Hao, to explore new options for people whose disease has stopped responding to standard treatments, according to a news release from University of Kentucky.

The early-stage clinical trial marks the first U.S. testing of Alveltamig, an immunotherapy designed to help the immune system better recognize and respond to small cell lung cancer. The study aims to address ongoing treatment challenges for patients whose cancer has progressed despite chemotherapy, radiation or prior immunotherapy.

Main Data That Support the Findings

Alveltamig is described as a trispecific T-cell engager, a type of immunotherapy that works by linking immune cells, called T cells, to cancer cells. According to the press release, the drug has three binding arms: two that attach more tightly to cancer cells and one that connects to T cells. This structure differs from Imdelltra (tarlatamab), a T-cell engager approved by the Food and Drug Administration (FDA) in 2024 for patients with small cell lung cancer whose disease worsened after chemotherapy and immunotherapy.

Imdelltra is a bispecific T-cell engager, meaning it uses two arms to connect cancer cells and immune cells. Alveltamig’s additional binding arm is intended to strengthen that connection, potentially improving how effectively immune cells respond to cancer cells.

“This is the next step forward in T-cell engager therapy for small cell lung cancer,” Hao said in the press release. “We’re testing a newer version of [Imdelltra] 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 [Imdelltra] another option.”

Early treatment experience at Markey has shown encouraging tolerability. The first patient treated with Alveltamig experienced no side effects from the initial dose and returned two weeks later for a second treatment that was also well-tolerated, according to the release. Patients enrolled in the trial are being closely monitored for potential side effects as dosing continues.

Hao also noted that the immunotherapy may have potential activity in brain metastases, which are common in small cell lung cancer. Brain involvement is often managed with whole-brain radiation therapy, a treatment associated with side effects such as fatigue, hair loss and cognitive problems. By improving control of disease throughout the body, immunotherapy could reduce or eliminate the need for brain radiation for some patients, according to Hao.

Details of the Phase 1 Trial Evaluating Alveltamig

The phase 1 clinical trial of Alveltamig is the first U.S.-based study of the drug, following an earlier trial conducted in China that showed the treatment was well-tolerated among patients. The U.S. trial plans to enroll patients at six sites nationwide.

UK Markey Cancer Center is the first of those sites to open the trial and treat a patient. Additional centers, including Case Comprehensive Cancer Center, are preparing to begin enrollment.

Markey’s role as the initial U.S. site is tied to its designation as a National Cancer Institute-designated Comprehensive Cancer Center, one of 57 in the country. This designation allows the center to offer access to clinical trials that study new treatments before they are widely available.

According to the release, the trial is intended for patients with small cell lung cancer, a disease that is often diagnosed at an advanced stage. While patients may initially respond to chemotherapy and radiation, the cancer frequently returns, creating a need for additional treatment approaches when standard options are no longer effective.

“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.”

What is the Safety of Alveltamig?

Patient safety is a central focus of the Alveltamig trial. The press release notes that patients receiving the treatment are carefully monitored for side effects throughout the study. In the initial experience at Markey, the first patient did not experience side effects after the first dose and tolerated a second dose given two weeks later.

The phase 1 design of the study is intended to closely evaluate how patients tolerate the therapy while researchers gather early information about how the drug behaves in the body. This careful monitoring is particularly important for immunotherapies that engage the immune system in new ways.

Researchers will continue to assess side effects as additional patients enroll and receive treatment. The information collected during this phase of the trial will help guide future studies of Alveltamig in small cell lung cancer and determine next steps for ongoing clinical development.

Reference

1. “Markey Cancer Center Treats 1st Patient in US with New Lung Cancer Therapy.” News Release. University of Kentucky.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.