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SEOUL, South Korea -- Treatment with the bispecific antibody ubamatamab alone or in combination with the PD-1 inhibitor cemiplimab (Libtayo) appeared to be safe and demonstrated activity in patients with recurrent ovarian cancer, a phase I study suggested.

In this monotherapy and combination dose-escalation study, dosages up to 800 mg IV weekly and 250 mg IV weekly, respectively, were considered tolerable per protocol-defined criteria, reported Roisin O'Cearbhaill, MD, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College in New York City, during the International Gynecologic Cancer Society annual meeting.

As for clinical activity, responses were observed at monotherapy dose levels ranging from 20 to 800 mg, and at dose levels ranging from 10 to 250 mg for the combination.

Ubamatamab (REGN4018) is a fully human bispecific antibody that binds mucin 16 (MUC16), a cell surface protein overexpressed in ovarian cancer, and CD3 on T cells. "In preclinical studies, ubamatamab was shown to demonstrate dose-dependent killing of MUC16-expressing ovarian cancer cells," O'Cearbhaill said. "Cemiplimab has been shown to enhance that activity."

Looking at adverse events (AEs), pain and cytokine release syndrome (CRS) were the most common across the monotherapy group (79.7% and 75.7%, respectively) and the combination therapy group (71.4% and 68.6%). CRS was low-grade in all patients, with no grade ≥3 CRS.

Grade ≥3 treatment-related AEs occurred in 43% of patients overall, and included pain, anemia, and neutropenia. There were two dose-limiting toxicities of grade 4 neutropenia lasting more than 7 days, and one patient with grade 4 hemophagocytic lymphohistiocytosis/macrophage activation syndrome.

Immune effector cell-associated neurotoxicity occurred in two patients during ubamatamab step-up dosing, with both events resolved with steroids in 48 hours.

Focusing on clinical activity among 42 patients who received at least one dose of ubamatamab monotherapy, the objective response rate (ORR) was 14.3% by RECIST 1.1 criteria, and 33.3% by cancer antigen (CA)-125 criteria. The median duration of response (DOR) was 13.7 months, and median progression-free survival (PFS) was 2.8 months, with 6-month PFS rates of 30.7% and 12-month rates of 16.7%.

Among the 22 patients treated with the combination of ubamatamab and at least one dose of cemiplimab, the ORR was 18.2%, and 22.7% by CA-125 criteria. The median DOR was 8.3 months, and median PFS was 4.9 months, with 6-month and 12-month PFS rates of 47.6% and 23.8%, respectively.

All 10 of the patients who achieved an objective response in the study had a CA-125 response.

O'Cearbhaill also noted that there was "a general trend toward increased activity of tumor-involved MUC16 expression" when assessing ORR, CA-125 response, and PFS in the monotherapy subset.

This enrolled 109 patients (74 in the monotherapy subset and 35 in the combination subset) with confirmed ovarian cancer with serum CA-125 ≥2 times the upper limit of normal, who had at least one previous line of platinum-containing therapy (median five lines).

Median age was 61 in the monotherapy group and 63 in the combination group. Visceral metastases were present in 33.8% and 42.9% of patients, respectively.

Median duration of exposure was 11.9 weeks in the monotherapy cohort, and 11 months with ubamatamab and 12 months with cemiplimab in the combination cohort.

An ongoing randomized phase II study will establish the preferred ubamatamab dose, evaluate anti-tumor activity contributed by cemiplimab, and explore MUC16 immunohistochemistry for patient selection.

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