Dr Villalona-Calero on the Investigation of KB-0742 in Relapsed/Refractory Solid Tumors

Miguel Villalona-Calero, MD, director, Early Phase Therapeutics Program, co-program leader, Developmental Cancer Therapeutics Program, professor, Department of Medical Oncology & Therapeutics Research, City of Hope, discusses interim data from a phase 1/2 (NCT04718675) investigation of KB-0742 in patients with relapsed/refractory solid tumors or non-Hodgkin lymphoma, and highlights the ongoing evaluation of the agent’s safety.

The first-in-human, open-label study consists of a dose-escalation phase evaluating the safety and tolerability of KB-0742. This will be followed by a dose-expansion phase that aims to further assess the agent’s safety and activity in patients with transcription-dependent tumors cohorts.

Investigators have seen tumor shrinkage in multiple patients treated with KB-0742, particularly in those with myxoid liposarcoma. This indicates the potential sensitivity of this tumor type to KB-0742, Villalona-Calero begins. Villalona-Calero states that data from the dose-escalation phase were previously presented. Investigators now aim to verify the drug’s efficacy in transcriptionally driven tumors in the ongoing dose-expansion phase. The safety and pharmacokinetic activity of a given agent are primarily evaluated in a phase 1 dose escalation, he notes. Among those with myxoid liposarcoma in this study, 1 patient exhibited a partial response (PR) that was sustained for longer than 6 months. Another patient experienced tumor shrinkage without meeting PR criteria, but still experienced benefit from the drug, Villalona-Calero notes.

Nausea and vomiting were the most commonly observed adverse effects (AEs), and they wereeffectively managed with antiemetics, he continues. Preference was given to granisetron over ondansetron due to concerns about potential drug-to-drug interactions and QTc prolongation, Villalona-Calero explains. Administered an hour prior to dosing, granisetron successfully preventing nausea and vomiting in most patients, he says.

Additionally, investigators noted potential central nervous system effects with KB-0742, Villalona-Calero expands. For instance, 2 patients in the study developed seizures that werecontrolled with medication, suggesting that the drug might be crossing the blood-brain barrier. Understanding responses and AEs associated with KB-0742 remains a primary objective in the ongoing dose-expansion phase of the study, Villalona-Calero concludes.