Ubamatamab Shows Some Activity in Recurrent Ovarian Cancer

Treatment with the investigational bispecific antibody ubamatamab (REGN4018) alone or in combination with the PD-1 inhibitor cemiplimab (Libtayo) appeared to be safe and demonstrated activity in patients with recurrent ovarian cancer, according to updated results of a phase I study presented at the International Gynecologic Cancer Society (IGCS) annual meeting by Roisin O’Cearbhaill, MD, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College in New York City.

In this exclusive MedPage Today video, Richard Penson, MBBS, of Mass General Cancer Center at Massachusetts General Hospital in Boston, discusses the results from the trial.

Following is a transcript of his remarks:

So Regeneron developed these really great antibodies, and so the 4018, ubamatamab, that’s a CD3 a T-cell receptor with MUC16 [mucin 16]/CA [cancer antigen]-125. So this bispecific, and a bispecific is a monoclonal that gets the end clip, so the hinge is bigger and you can clack heads together, the T-cell and the tumor cell. And that’s the first signal, the equivalent of MHC [major histocompatibility complex] binding, the T-cell receptor. And then you want a second signal. So this study presented for the first time the addition of cemiplimab, which is a PD-1 antibody — that’s that amplification signal. But there’s ongoing trials looking at REGN5668, which is a CA-125-CD28 costimulatory antibody. So you engage and you amplify the immune response.

The results were a bit disappointing, I thought — response rate of 14% for ubamatamab and the combination 18% as an objective response rate. And sort of the duration of response, which was really good in the single agent or less, like nearly half, 14 down to 8 months with the combination, really spoke to this is sort of phase I data, that is sort of early.

So we are starting to get close to the dose. There’s a randomized phase II. We know the toxicity profile, cytokine release syndrome, pain, anemia, neutropenia, and a signal. So trying to get, it’s a bit of a holy grail to target CA-125. It feels like such a great target. Surely we should be able to get therapeutics against this. So it remains an exciting platform.

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