Commentary
Video
Author(s):
Pavlos Msaouel, MD, PhD, assistant professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the rationale behind a phase 2 trial (NCT06444880) of ubamatamab (REGN4018) alone or in combination with cemiplimab-rwlc (Libtayo) in MUC16-expressing renal medullary carcinoma (RMC) and epithelioid sarcoma following progression.
RMC is notably aggressive and particularly affects younger individuals of African descent, Msaouel begins, stating that the average survival from diagnosis to death, if untreated, is between 3-4 months. The goal of this trial is to improve outcomes for these patients through a "Bench to Bed" translational program that integrates biological rationale, preclinical models, and clinical trial development, Msaouel explains. Previous efforts have led to the activation and completion of 3 clinical trials, with the fourth trial scheduled for activation in September. This upcoming trial expands beyond RMC to include epithelioid sarcoma.
Both RMC and epithelioid sarcoma are characterized by the loss of SMARCB1, which leads to the expression of MUC16 in approximately 60% to 80% of patients with either cancer, he continues. MUC16 encodes the MUC16 protein, which is expressed on the surface of cancer cells and is cleaved into CA125, an antigen released into the bloodstream, Msaouel says.
Msaouel explains that the bispecific antibody ubamatamab targets both MUC16 on cancer cells and CD3 on T cells. This dual targeting facilitates the recruitment of T cells to the tumor site, enhancing the immune system's ability to attack the tumor, he reports. The binding of ubamatamab to MUC16-expressing cancer cells and CD3-expressing T cells is designed to bring immune cells into proximity with the cancer cells, thereby activating an immune response against the tumors.
By leveraging the dual targeting mechanism of ubamatamab, the trial aims to provide a novel therapeutic approach for patients with these aggressive cancers, potentially improving their prognosis and expanding treatment options, Msaouel concludes.