A study comparing the efficacy and safety of golcadomid plus R-CHOP versus placebo plus R-CHOP in patients with previously untreated, high-risk large B-cell lymphoma

The term “large B-cell lymphoma” (LBCL) encompasses various aggressive forms of B-cell lymphomas characterized by large, dysplastic B cells. The most common form is diffuse large B-cell lymphoma (DLBCL, NOS). It also includes highly aggressive B-cell lymphomas with specific genetic alterations (such as MYC, BCL2, or BCL6, known as “double-hit” or “triple-hit” lymphomas). Other examples include primary mediastinal large B-cell lymphoma, which primarily occurs in the chest cavity of young adults, as well as the leg-type primary cutaneous DLBCL. Slow-growing lymphomas that transform into a large-cell lymphoma (transformed lymphomas) also belong to this group. Other subtypes include EBV-positive DLBCL, which is more common in older or immunocompromised individuals, and T-cell/histiocyte-rich large B-cell lymphoma. These forms differ in their biology, prognosis, and treatment approach, but are often studied together in clinical trials. In these diseases, symptoms may include rapid enlargement of the lymph nodes and spread to other organs. Patients often report fever, night sweats, and weight loss. The exact cause of LBCL is unknown, but genetic mutations and infections such as the Epstein-Barr virus may play a role. Patients with newly diagnosed LBCL are typically treated with a combination of chemotherapy and immunotherapy, such as the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Treatment depends on the patient’s overall condition and the progression of the disease. In principle, however, a cure is possible in many cases. Completed studies have already found evidence suggesting that adding medication to the R-CHOP regimen could improve survival rates. Golcadomid belongs to the class of CELMoD™ agents (Cereblon E3 ligase modulators) and works by specifically degrading proteins that are important for the growth and survival of cancer cells. By binding to the protein Cereblon, Golcadomid leads to the degradation of key proteins in lymphoma cells and simultaneously activates the immune system—particularly T cells and natural killer cells—to attack the cancer cells. The drug has not yet been approved.

The goal of the GOLSEEK-1 study (Phase 3 trial) is to investigate the efficacy and safety of treatment with Golcadomid in combination with R-CHOP chemotherapy in a larger number of patients with high-risk LBCL. As part of the study, patients will be randomly assigned to two groups. Group 1 will receive the study drug Golcadomid in combination with R-CHOP chemotherapy. Group 2 will receive a placebo combined with R-CHOP. A placebo is a dummy medication that contains no active ingredient. A total of 6 treatment cycles, each lasting 21 days, will be administered. This is a double-blind study, meaning that neither the medical staff nor the patient knows which medication (Golcadomid or placebo) is being administered. Treatment as part of the study will continue for up to 67 months, during which the efficacy of the therapy and the occurrence of side effects from the various medications will be evaluated. The key factor is whether or when the disease progresses again during treatment. The primary endpoint of the study is the disease-free survival rate after 67 months.

Women and men aged 18 to 80 with newly diagnosed high-risk LBCL (including DLBCL and T-cell/histiocyte-rich LBCL) who have not received prior treatment are eligible to participate in the study. Patients with Burkitt lymphoma or central nervous system involvement are not eligible to participate.