The International Gynecologic Cancer Society (IGCS) annual meeting recently featured the presentation of updated results from a phase I study on the investigational bispecific antibody ubamatamab (REGN4018). This antibody, when used alone or in combination with the PD-1 inhibitor cemiplimab (Libtayo), demonstrated both safety and activity in patients with recurrent ovarian cancer. In this article, we will delve into the significance of the findings and their potential implications for the future of ovarian cancer treatment.
The Mechanism of Ubamatamab
Ubamatamab, also known as CD3 a T-cell receptor with MUC16/CA-125, is a bispecific monoclonal antibody developed by Regeneron. The unique characteristic of this antibody lies in its ability to facilitate the interaction between T-cells and tumor cells. By engaging the T-cell receptor and amplifying the immune response through the addition of cemiplimab, the antibody aims to enhance the effectiveness of ovarian cancer treatment. There are ongoing trials investigating the use of REGN5668, a CA-125-CD28 costimulatory antibody, which further strengthens the immune response.
The phase I study presented at the IGCS annual meeting reported a response rate of 14% for ubamatamab as a monotherapy and 18% for the combination therapy with cemiplimab. While these response rates may seem modest, it is important to note that the study is still in its early stages. The duration of response was also observed to be slightly shorter in the combination therapy group compared to the monotherapy group. However, this data is to be expected in phase I studies, as the primary objective is to establish the appropriate dosage and evaluate the toxicity profile. Common adverse events observed included cytokine release syndrome, pain, anemia, and neutropenia.
The development of targeted therapies against CA-125, a tumor-associated antigen abundantly expressed in ovarian cancer, remains an exciting prospect. Despite the initial disappointing response rates observed in this study, ubamatamab holds promise as a potential therapeutic option. The ongoing phase II trial, which aims to further evaluate its efficacy, will provide valuable insights into its potential role in ovarian cancer treatment.
The investigational antibody ubamatamab, either as a monotherapy or in combination with cemiplimab, has demonstrated both safety and activity in patients with recurrent ovarian cancer. While the initial response rates may not be as high as desired, it is crucial to consider the early stage of the study. The ongoing trials and the growing understanding of the toxicity profile and immune response amplification will contribute to the future optimization of ubamatamab treatment. With CA-125 as a target, the development of effective therapeutics for ovarian cancer remains a promising endeavor in the field of oncology.