In a recent presentation at the International Gynecologic Cancer Society annual meeting, Dr. Roisin O’Cearbhaill discussed the safety and efficacy of ubamatamab (REGN4018), an investigational bispecific antibody, in patients with recurrent ovarian cancer. The results of the phase I study showed that ubamatamab, either alone or in combination with the PD-1 inhibitor cemiplimab (Libtayo), demonstrated activity against the disease.
The Science behind Ubamatamab
Ubamatamab is a bispecific antibody that targets both the CD3 receptor on T-cells and the MUC16/CA-125 antigen on tumor cells. This unique design allows the antibody to bring T-cells in close proximity to tumor cells, leading to the activation of the immune response. The addition of cemiplimab, a PD-1 antibody, acts as an amplification signal, further enhancing the immune response against the cancer cells.
Although the results of the study showed promise, the objective response rate was modest, with a 14% response rate for ubamatamab alone and an 18% response rate for the combination therapy. Moreover, the duration of response was shorter in the combination therapy group compared to the single-agent therapy. These findings indicate that the study is still in its early stages, and further research is needed to optimize the dosing and efficacy of ubamatamab in the treatment of ovarian cancer.
Addressing Toxicity and Side Effects
One of the challenges in developing targeted therapies for ovarian cancer is minimizing toxicity and side effects. The study reported several adverse events associated with ubamatamab, including cytokine release syndrome, pain, anemia, and neutropenia. These side effects highlight the need for careful monitoring and management of patients receiving ubamatamab or combination therapy.
The Quest for Targeting CA-125
CA-125, the antigen targeted by ubamatamab, is a known biomarker for ovarian cancer. Many researchers and clinicians have long regarded it as a promising target for therapeutic interventions. However, despite the potential, the development of effective therapeutics against CA-125 has proven to be challenging. The ongoing trials with REGN5668, a CA-125-CD28 costimulatory antibody, represent another avenue of exploration in this quest.
Bispecific antibodies, like ubamatamab, offer an exciting avenue for the treatment of ovarian cancer. By simultaneously engaging the immune system and tumor cells, bispecific antibodies aim to enhance the immune response against cancer cells. While the results of this phase I study may be considered preliminary, they provide insights into the potential of this novel class of therapeutics.
The preliminary results of the phase I study evaluating ubamatamab in recurrent ovarian cancer patients showed promising activity. The combination of ubamatamab with cemiplimab demonstrated an objective response rate of 18%, albeit with a shorter duration of response compared to the single-agent therapy. Further research and development are necessary to optimize dosing, minimize toxicity, and improve efficacy. As scientists continue their quest to target CA-125, bispecific antibodies remain an exciting platform with the potential to revolutionize the treatment landscape for ovarian cancer.