Substudy to Evaluate the Drug Zilovertamab Vedotin in Children and Young Adults with Certain Forms of Blood Cancer or Solid Tumors (MK-9999-01A/LIGHTBEAM-U01)

Among other things, the study examines so-called hematologic cancers—including leukemias and lymphomas, which are types of cancer that affect the blood or the lymphatic system. B-cell acute lymphoblastic leukemia (B-ALL), diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma—as well as neuroblastoma and Ewing sarcoma—are more common in children and young adults. Treatment is generally tailored to the specific disease and may include chemotherapy, radiation therapy, immunotherapy, or stem cell transplantation. In some cases, patients may not respond to these standard therapies, or the cancer may recur after initial treatment. In various types of cancer—such as B-ALL, DLBCL, Burkitt lymphoma, neuroblastoma, and Ewing sarcoma—many of the affected cancer cells share a specific surface marker: the so-called ROR1 protein (Receptor tyrosine kinase-like Orphan Receptor 1). This protein is rarely found on healthy cells but is present in higher quantities in these types of cancer—which is precisely why it can be used as a target for cancer drugs. The new drug zilovertamab vedotin is what’s known as an antibody-drug conjugate. It combines an antibody that specifically binds to the ROR1 protein on cancer cells (zilovertamab) with a cytotoxic agent (vedotin) that is specifically delivered into the cancer cell. The goal is to spare healthy cells as much as possible while selectively killing the cancer cells.

The goal of the LIGHTBEAM-U01 study is to investigate the efficacy and safety of zilovertamab vedotin in patients with relapsed or refractory B-ALL, DLBCL, Burkitt lymphoma, neuroblastoma, or Ewing sarcoma. The study will be conducted in two phases. Phase 1 will first determine which dosage of the drug is well tolerated, with a focus on potential side effects. Phase 2 will then assess whether and how well the drug works against the respective cancer—that is, whether it stops tumor growth or even shrinks the tumor, for example. Treatment is administered as an intravenous infusion on Day 1 of a 21-day cycle, meaning every three weeks. The therapy can be repeated over several cycles as long as it remains effective and is well tolerated. In addition, blood tests, physical examinations, and imaging procedures (e.g., MRI, CT) are performed regularly throughout the course of treatment to closely monitor the drug’s effectiveness and any potential side effects.

Children and young adults aged 6 months to 25 years with certain types of cancer—including B-cell acute lymphoblastic leukemia (B-ALL), diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, neuroblastoma, or Ewing sarcoma. A prerequisite is that the disease has recurred following prior treatment (recurrence) or has not responded adequately to previous therapies (refractory).