Miguel Villalona-Calero, MD, discusses interim data from a phase 1/2 investigation of KB-0742 in patients with solid tumors or non-Hodgkin lymphoma.

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.

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Miguel Villalona-Calero, MD, discusses interim data from a phase 1/2 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.


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 the unique mechanism of action of the CDK9 inhibitor KB-0742 in patients with relapsed/refractory solid tumors or non-Hodgkin lymphoma (NHL).

KB-0742 is under investigation in a phase 1 dose-escalation and -expansion trial (NCT04718675) that is currently enrolling patients with relapsed/refractory NHL or solid tumors, including triple-negative breast cancer (TNBC), non–small cell lung cancer, epithelial ovarian cancer, or sarcoma. In part 1, the dose-escalation part, patients will receive escalating doses of KB-0742 to identify the maximum tolerated dose. In part 2, the cohort expansion part, cohort A will enroll patients with relapsed/refractory solid tumors with 

 amplification or overexpression. Cohort B will enroll patients with relapsed/refractory small cell lung cancer and soft tissue sarcomas with transcription factor dysregulation.

As KB-0742 is an oral agent, it may support positive quality of life outcomes, since many patients prefer this administration method over others, Villalona-Calero says. Another potential benefit of KB-0742 is its long half-life, Villalona-Calero notes. Some agents must be given at higher doses over shorter periods of time so they can hit their targets, Villalona-Calero explains. However, these agents are often not as potent as they need to be and thus can cause unnecessary or toxic off-target effects, Villalona-Calero emphasizes. Along with their limited target action, some agents only downregulate their targets for a short time, Villalona-Calero says.

Preclinical data have shown that KB-0742 has a long half-life and therefore stays on and interacts with its target longer than other agents, Villalona-Calero explains. For instance, 1 preclinical study of KB-0742 showed correlations between tumor growth inhibition and 

 expression or amplification and demonstrated maximal inhibition rates of 100% and 89% in 2 TNBC patient-derived organoids. KB-0742 is also a more selective agent, causing fewer off-target effects compared with other agents, Villalona-Calero concludes.

Miguel Villalona-Calero, MD, discusses the unique mechanism of action of the CDK9 inhibitor KB-0742 in patients with relapsed/refractory solid tumors or non-Hodgkin lymphoma.


Miguel Villalona-Calero, MD

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

Dr. Villalona-Calero on KB-0742 in Solid Tumors and NHL