REGN5668 Combo Yields Preliminary Activity in Recurrent Ovarian/Endometrial Cancer

At the 2026 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (SGO), CancerNetwork® spoke with Roisin E. O’Cearbhaill, MD, about a poster she shared on a phase 1/2 study which evaluated REGN5669 in combination with targeted therapies as a treatment for patients with recurrent ovarian or endometrial cancer.¹

In the ovarian cancer cohort of module 1, or the dose expansion portion, patients received REGN5668 plus cemiplimab-rwlc (Libtayo) and fianlimab, whereas in the endometrial cancer cohort, patients received REGN5668 plus cemiplimab. The primary end point of this portion was objective response rate (ORR) per RECIST v1.1 guidelines; secondary end points included other efficacy and safety outcomes, and the incidence of grade 3 or higher laboratory abnormalities.

In module 2, or the dose escalation portion, of the trial, patients received sarilumab (Kevzara), as well as REGN5668 plus ubamatamab. The primary end points were safety outcomes, the incidence of grade 3 or higher laboratory abnormalities, and the concentration of REGN5668 in serum; secondary end points included efficacy outcomes, CA-125 change from baseline, and concentration of REGN5668 in serum over time.

Cearbhaill answered questions about the trial regimens, as well as the logistical hurdles involved with implementing REGN5668 into clinical settings.

Cearbhaill is research director of Gynecologic Medical Oncology Service, clinical director of Solid Tumors in the Cellular Therapy Service, and associate attending physician at Memorial Sloan Kettering Cancer Center.

Transcript:

Which targeted therapies is [REGN5668] being added to?

In the module 1,, REGN5668 is being added to an anti-PD-1 [agent], cemiplimab, and also to an anti-LAG-3 agent, fianlimab. In the dose escalation, there was nice data showing preliminary clinical activity. We're now moving on to the expansion phase, and that combination will be tested.

What is the difficulty level of implementing the agent into oncology centers in regard to toxicity training or administration?

Like any new therapy, there's definitely a learning curve with the ubamatamab, which is a sister study that's the bispecific that's targeting MUC16xCD3, [which is] expressed on T cells. That has required step-up dosing, so we often start at quite a low dose, like 1 mg, and then we escalate up to the intended dose. Currently that is requiring admissions to the hospital. For REGN5668, the great news is that we have not seen significant cytokine release syndrome, and it's extremely well tolerated. It’s been a lot easier to implement in the clinic.

Reference

O’Cearbhaill RE, Bouberhan S, Nieuwenhuysen EV, et al. A phase 1/2 study of REGN5668, a MUC16×CD28 costimulatory bispecific antibody, in combination with other targeted therapies, in patients with recurrent ovarian or endometrial cancer: trial in progress update. Presented at the 2026 SGO Annual Meeting on Women’s Cancer; April 10-13, 2026; San Juan, PR. Poster 266.