Phase 1 Success of Targeting MUC16 in Patients With Recurrent Ovarian Cancer

David O’Malley, MD

Ubamatamab, a novel MUC16 antibody, demonstrated evidence of durable responses in patients with recurrent ovarian cancer and showed an acceptable safety profile, according to a study presentation by David O'Malley, MD at the 2022 European Society of Oncology (ESMO) Annual Congress.¹

The phase 1 first-in-human study of ubamatamab (REGN4018; NCT03564340) included a total of 78 patients in the trial were given ubamatamab. Enrolled patients had a median number of 4.5 prior therapies (range 1-17) and the median duration of exposure was 12 weeks (range 0.4-117).

Findings concluded objective responses to be observed between 20–800 mg doses (n = 50). The overall response rate (ORR) for the 42 patients receiving 1 or more full dose was 14.3% (95% CI, 5.4-28.5) while the disease control rate (DCR) was 57.1% (41.0-72.3). Further, the median duration of response was 12.2 months.

For patients without baseline visceral metastases (n = 29) the ORR was 20.7% (8.0-39.7) and the disease control rate (DCR) was 72.4% (52.8-87.3). An exploratory analysis examining patients with greater than 75% of tumor cells with 2+ baseline MUC16 immunohistochemical staining and ≥ 1 dose of ≥ 20 mg (n = 13) revealed an ORR of 30.8% (9.1-61.4), and DCR of 61.5% (31.6-86.1). There was no definitive dose-response relationship observed for safety or efficacy between 20-800 mg.

The most common TEAEs were cytokine release syndrome (73.1%), all of which were grade 1 or 2, and pain (87.2%), which primarily occurred in weeks 1 or 2 of initial step-up dosing. The most common grade 3 or higher TEAEs included anemia (23.1%) and abdominal pain (19.2%).

Based on data from this study of ubamatamab, a randomized phase 2 expansion has been initiated.

In an interview with Targeted Oncology^TM during the 2022 ESMO Annual Congress, O’Malley, a professor in the Department of Obstetrics and Gynecology at The Ohio State University College of Medicine and the director of the Division of Gynecologic Oncology at the OSUCCC–James, further discussed the phase 1 study of ubamatamab in ovarian cancer.

Can you discuss ubamatamab and its mechanism of action?

Ubamatamab is a bispecific antibody, which is directly against the MUC16 and CD3 cells. It brings those immune cells in close proximity to the MUC16 expressing ovarian cancer cells, leading to cell death. MUC16 is expressed in about 80 to 90% of ovarian cancer patients I should say.

What are we seeing preclinically with this agent in recurrent ovarian cancer cells?

We presented an efficacy population of those patients who received at least 1 dose at 20 mg or more, which was 42 patients. What we saw were overall response rates of 14%. We looked at the exploratory group of patients that had high MUC16 expression. In the efficacy cohort, there were 13 patients that had that high expression, defined as greater than 75% of tumor cells expressing 2 or more MUC16 IHC.

We found a 31% response rate in those 13 patients. That's an exploratory analysis but though that biomarker continues to be developed, it is an exciting option moving forward with ubamatamab.

Can you talk about the phase 2 study? What is its status and what are the key goals?

There are currently 3 cohorts which are expanding to different dose levels, as well as in combination with their PD-1 inhibitors. We are going to have 3 cohorts within the expansion cohort.

Now, as a single agent, it's exciting. But combining that with a potentially checkpoint inhibitor is a novel option moving forward. It's important to note that of those responses that we saw at the single agent, we had 2 patients at the time of the data cut-off that continued therapy, with 1 beyond 15 months, and 1 beyond almost 2 years. We are seeing responses which are durable and common.

References:

1. Van Nieuwenhuysen E, O'Malley D, Cearbhaill R.E., et al. Ubamatamab (REGN4018, MUC16xCD3 bispecific antibody) monotherapy in patients with recurrent ovarian cancer (OC): Phase I dose-escalation analysis. Ann Oncol. 2022;33(suppl 7):523MO. doi:10.1016/annonc/annonc1054