Dr O'Cearbhaill on the Evaluation of REGN5668 in Recurrent Ovarian or Endometrial Cancer

“We’re looking at combining REGN5668 with cemiplimab in ovarian cancer, and an anti–LAG3 agent called fianlimab. Basically, [with] those two agents of cemiplimab, [which is an] anti–PD-1 [agent], and the anti-LAG3 agent, the idea is that they will help boost that immune activation.”

Roisin E. O’Cearbhaill, MD, research director of the Gynecologic Medical Oncology Service, clinical director of the Solid Tumor, Cellular Therapy Service, and associate attending physician at Memorial Sloan Kettering Cancer Center, discussed the design and rationale of a phase 1/2 trial (NCT04590326) evaluating the costimulatory bispecific antibody REGN5668 in combination with different targeted therapies for patients with recurrent ovarian or endometrial cancer.

The trial was designed with 2 modules. Module 1 comprises the dose-expansion portion of the study, O’Cearbhaill explained. This phase builds upon prior dose-escalation work and utilizes the recommended phase 2 dose of REGN5668, in combination with the anti–PD-1 agent cemiplimab-rwlc (Libtayo) and the anti–LAG3 antibody, fianlimab. The scientific rationale for this assessing these agents in combination centers on enhancing immune activation through complementary mechanisms. PD-1 inhibition with cemiplimab works to reinvigorate exhausted T cells, and targeting LAG3 is thought to further relieve immune suppression, potentially leading to a more robust antitumor immune response. The addition of REGN5668 to these agents is thought to further modulate the tumor environment or related signaling pathways in a way that augments the efficacy of checkpoint blockade, O’Cearbhaill explained.

Within the dose-expansion cohort, patients must have recurrent ovarian cancer, measurable disease based on standard radiographic criteria, and an adequate performance status to ensure they can tolerate combination therapy. Additionally, patients must have elevated CA-125 levels that are at least twice the upper limit of normal, because it serves as a clinically relevant biomarker of disease activity. To minimize confounding safety risks, patients cannot be on high-dose corticosteroids and cannot have untreated or active central nervous system metastases.

The primary end point of the dose-expansion phase is objective response rate per RECIST 1.1 criteria. Secondary end points include pharmacokinetic assessments, such as serum concentrations of REGN5668, as well as detailed safety evaluations to characterize the toxicity profile of the combination regimen. Additional exploratory and secondary measures include changes in CA-125 levels from baseline.