Dr Van Tine on the Investigation of KB-0742 in R/R Solid Tumors

Brian A. Van Tine, MD, PhD, professor of medicine, Division of Oncology, Section of Medical Oncology, the Washington University School of Medicine, Siteman Cancer Center, discusses the ongoing evaluation of the CDK9 inhibitor KB-0742 in a phase 1 trial (NCT04718675) in patients with relapsed/refractory solid tumors or non-Hodgkin lymphoma (NHL), detailing the key enrollment criteria.

The dose-escalation portion of the trial determined the maximum tolerated dose of KB-0742, Van Tine begins. Part 1 of the trial established 60 mg as the recommended phase 2 dose of KB-0742 after doses escalated from 10 mg. Although the first part of the trial included patients with relapsed/refractory solid tumors or NHL who were not selected for MYC amplification, part 2 will include patients in cohort A who have MYC-dependent solid tumors, including non–small cell lung cancer, small cell lung cancer, triple-negative breast cancer, and ovarian cancer. Cohort B will feature patients with other transcriptionally addicted tumors.

The key inclusion criteria are different for each arm of the study in part 2, Van Tine expands. For example, in a patient whose disease is identified as MYC amplified through a genomics report, further screening for activated MYC transcription is required for enrollment into cohort A, since MYC could help predict the success with KB-0742, Van Tine says.

In another arm, investigators are evaluating patients with transcription factor–driven sarcomas, which could include soft tissue sarcomas, Ewing's sarcoma, alveolar rhabdomyosarcoma, NUT midline carcinoma, or chordoma.

Although enrolling patients for cohort B is relatively straightforward since investigators have prior knowledge of which sarcomas harbor transcription-factor fusions, there are challenges involved in finding and enrolling patients with MYC-amplified solid tumors, Van Tine says. He concludes that a concerted effort to find more patients with tumors harboring MYC amplification will be vital for the development of KB-0742.