Phase I success in targeting MUC16 in patients with recurrent ovarian cancer

In an interview with Targeted Oncology during the EMSO Annual Conference, David O’Malley, MD, discusses a phase I study of ubamatamab in ovarian cancer.

Ubamatamab, a new antibody to MUC16, has shown evidence of durable responses in patients with recurrent ovarian cancer and demonstrated an acceptable safety profile, according to a study presentation presented by David O’Malley, MD at the 2022 European Society of Oncology (ESMO) annual conference.1

The first-of-its-kind human study of obamatamab (REGN4018; NCT03564340) included a total of 78 patients in the trial who were given obamatamab. Enrolled patients had a mean number of previous treatments 4.5 (range 1-17) and median duration of exposure was 12 weeks (range 0.4-117).

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

For patients without primary 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 >75% of tumor cells with immunohistochemical staining +2 + MUC16 and ≥ 1 dose of 20 mg (n = 13) revealed an ORR of 30.8% (9.1-61.4), and a DCR of 61.5% (31.6-86.1). No specific dose-response relationship was observed with regard to safety or efficacy between 20-800 mg.

The most common cytokine release syndrome was (73.1%), all of which were of first or second degree, and pain (87.2%), which mainly occurred in the first or second week of initial dosing. Grade 3 or higher of the most common TEAEs included anemia (23.1%) and abdominal pain (19.2%).

Based on data from this ubamatamab study, a phase 2 randomized expansion was initiated.

In an interview with Targeted OncologyTM During the 2022 ESMO Annual Conference, O’Malley, professor in the department of obstetrics and gynecology at The Ohio State University School of Medicine and director of gynecological oncology at OSUCCC-James, discussed the phase I study of ubamatamab in ovarian cancer.

Can you discuss ubamatamab and its mechanism of action?

Ubamatamab is a bispecific antibody, which is a direct antagonist of MUC16 and CD3 cells. It brings these immune cells close to MUC16 expressing ovarian cancer cells, which leads to cell death. I must say that MUC16 appears in about 80-90% of ovarian cancer patients.

What do we see preclinically with this agent in recurrent ovarian cancer cells?

We presented an effective cohort of patients who received at least one 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 with high MUC16 expression. In the efficacy group, there were 13 patients who had this high expression, which was defined as greater than 75% of tumor cells expressing 2 or more MUC16 IHC.

We found a response rate of 31% in these 13 patients. This is an exploratory analysis but although development of this biomarker continues, it is an exciting option going forward with ubamatamab.

Can you talk about the second phase of the study? What is his condition and what are the main goals?

There are currently 3 groups expanding to different dosage levels, as well as in combination with their PD-1 inhibitors. We will have 3 groups within the expansion group.

Now, as a solo agent, it’s exciting. But combining that with a potential checkpoint disincentive is a new option going forward. It is important to note that among those responses we saw at the single agent, we had 2 patients at the time of the data interruption that continued treatment, with 1 after 15 months, and 1 patient after ~2 years. We are seeing persistent and common responses.

References:
  1. Van Nieuwenhuysen E, O’Malley D, Cearbhaill RE, et al. Ubamatamab (REGN4018, MUC16xCD3 bispecific antibody) monomer in patients with recurrent ovarian cancer (OC): a phase I dose-escalation analysis. Anne Oncol. 2022; 33 (Supplement 7): 523 MB. doi: 10.1016/declared/declared 1054