Dr Moore on the Design of a Phase 1/2 Study of Ubamatamab in Ovarian Cancer

Kathleen N. Moore, MD, MS, associate director, Clinical Research, Stephenson Cancer Center, director, Oklahoma TSET Phase I Program, professor, Section of Gynecologic Oncology, The University of Oklahoma College of Medicine, discusses the design of the ongoing, first-in-human, phase 1/2 study (NCT03564340) of the MUC16- and CD3-targeted bispecific antibody ubamatamab (REGN4018) alone or in combination with cemiplimab-rwlc (Libtayo) in patients with recurrent ovarian cancer.

This study has a new, formalized design in response to the expectations of the Oncology Center of Excellence Project Optimus, Moore begins, adding that bispecific antibodies are a class of agents with a different mechanism of action than those of agents previously used in patients with ovarian cancer, such as checkpoint inhibitors. In the phase 1 portion of the trial, ubamatamab was given weekly, and the toxicities associated with this agent were predominantly immune-related, such as low-grade cytokine release syndrome in weeks 1 and 2 that resolved by weeks 3 and 4, Moore explains. Once the patients experienced these toxicities, they did not occur again, she adds.

The toxicities associated with ubamatamab were not dose related because patients received a priming dose and an intermediate dose before receiving the full dose of the drug, Moore expands. In the dose-escalation portion of the trial, the toxicities were all seen in weeks 1 and 2, during which patients received ubamatamab at a flat dose. Therefore, these toxicities are schedule dependent, but not dose dependent. For this reason, during the first 2 weeks of this study, patients must receive ubamatamab in either an outpatient monitoring unit for at least 24 to 48 hours, or an inpatient setting, depending on each institution’s clinical trial setting, she notes.

In the phase 2 portion of this trial, patients receive the first cycle of ubamatamab weekly, so the investigators can administer a priming dose, the midpoint dose, and then the full dose. Once patients successfully reach cycle 2 of ubamatamab monotherapy, they receive this agent for 3 additional weeks in the outpatient setting, which patients can more feasibly tolerate, Moore continues.