Dr Msaouel on Ongoing Research With Bispecific Antibodies in RMC and Epithelioid Sarcoma

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.

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Pavlos Msaouel, MD, PhD, assistant professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses how exercise can influence risk for patients with sickle cell trait to develop renal medullary carcinoma (RMC).

High-intensity exercise may increase risk for a patient to develop RMC if they have the sickle cell trait, due to the damage that may occur in their kidneys, according to Msaouel. However, evidence has shown that moderate-intensity exercise can also be beneficial and lower the risk of developing this malignancy, Msaouel explains.

Moderate exercise correlates with low risk, no exercise is associated with moderate risk, and high-intensity exercise is associated with a high risk for developing RMC, Msaouel says. As such, it is important for patients to adjust their exercise routine accordingly to receive the health benefits of physical activity and reduce risk of RMC, Msaouel concludes. 

Pavlos Msaouel, MD, PhD, discusses how exercise can influence risk for patients with sickle cell trait to develop renal medullary carcinoma.

Dr. Msaouel on Reducing Risk Factors for Renal Medullary Carcinoma With Exercise 

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 for a phase II study (NCT03606174) evaluating sitravatinib in combination with nivolumab (Opdivo) in patients with metastatic or advanced urothelial cancer.

Sitravatinib is an oral TKI that targets the TAM receptors TYRO3, AXL, and MERTK, as well as VEGFR and c-MET, says Msaouel.

Investigators believe that inhibiting these receptors may enhance T cell-mediated antitumorimmune response. In turn, checkpoint inhibitors such as nivolumab could lead to enhanced activity in patients who progressed on anti—PD-1/PD-L1 therapy, concludes Msaouel.

Pavlos Msaouel, MD, PhD, discusses the rationale for a phase II study evaluating sitravatinib in combination with nivolumab in patients with metastatic or advanced urothelial cancer.

Pavlos Msaouel, MD, PhD

Articles

Dr Msaouel on Ongoing Research With Bispecific Antibodies in RMC and Epithelioid Sarcoma

Dr. Msaouel on Reducing Risk Factors for Renal Medullary Carcinoma With Exercise

Dr. Msaouel on Rationale for Sitravatinib/Nivolumab Combo in Urothelial Cancer